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Effects of platelet-rich plasma on bone healing in combination with autogenous bone and bone substitutes in critical-size defects: An animal experiment
Abstract
Objectives: An animal study was carried out to investigate the influence of platelet‐rich plasma (PRP) on the regeneration of bony defects.
Material and methods: Critical‐size defects in the forehead region of a mini‐pig were filled with randomly distributed combinations of autogenous bone, tricalcium‐phosphate granules (CeraSorb™), bovine spongious blocks (BioOss™) and a bovine bone inducing collagenous sponge (Colloss™) with and without PRP in two preparations (Cusasan, 3i). The animals were killed after 2, 4 and 12 weeks. The specimens were evaluated microradiographically and immunohistologically.
Results: Autologous bone (38±9.9%) and Colloss (52.6±4.0%) showed the highest remineralization rates at 2 weeks. The initial high expression of BMP‐2 in the Colloss®‐group gives evidence of an early initiation of bony regeneration. At 2 weeks PRP ad modum 3i was able to enhance bone healing significantly ( P =0.028) only when applied in combination with autogenous bone (62.8±1.6%). Four weeks after surgery, both PRP preparations did no longer increase bony regeneration in the autogenous groups. The osteoconductive effect of Bio‐Oss™ (38.7±5.5%) and CeraSorb™ (41±4.9%) was remarkable as well 4 weeks after surgery. Nevertheless, the addition of PRP hardly influenced bony regeneration, ceramic degradation or cytokine expression when bone substitutes were applied. At 12 weeks, the level of reossification had adjusted similarly in all groups.
Conclusion: PRP did not add additional benefit when xenogenic bone substitutes were used. However, a significant effect on bone regeneration was found in the autogenous group initially when PRP is added.
... By using a 5-mm rounger, a 5-mm bone defect was created in the central one-third of the zygomatic arch (Fig. 2B). 8,9 The periosteum at the remaining zygoma was preserved. The periosteal grafts, each about 4 Â 1.5 cm in size, were harvested from the cranium of 12 experimental animals. ...
... 25,26 Thus, we thought that a synergistic effect could be obtained by using periosteal graft combined with PRP. 3,9,27,28 In micro-CT analysis of new formed bone at 16th week, the periosteal graft þ PRP combination displayed significantly better results than control group regarding mean BV (mm 3 ) (P ¼ 0.028), and mean BMD (mm 2 ) (P ¼ 0.001). There were also significant differences between the groups regarding new bone regeneration scorings, histologically. ...
In this study, nanofibrous matrices of poly (L-lactic acid)-hydroxyapatite (PLLA-HAp) were successfully fabricated by 3-dimensional (3D) electrospinning for use in the treatment of irregular bone damages. Compressibility analysis showed that 3D nanofibrous grafts occupied at least 2-fold more volume than their 2D form and they can easily take shape of the defect zone with irregular geometry. Moreover, the compression moduli of the PLLA and PLLA-HAp grafts were calculated as 8.0 ± 3.0 kPa and 11.8 ± 3.9 kPa, respectively, while the strain values of the same samples at the maximum load of 600 kPa were 164 ± 28 % and 130 ± 20%, respectively. Treatment of the grafts with aqueous NaOH solution increased the surface roughness and thus the alloplastic graft materials (PLLA-HAp/M) protecting the fiber morphology were produced successfully. Then, platelet-rich plasma (PRP) was loaded into the surface modified grafts and activated with 10% CaCl2. The efficiency of the activation was evaluated with flow cytometry and it was found that after activation the percentages of CD62 (P-selectin) and CD41/61 (glycoprotein IIb/IIIa) proteins increased approximately 4-fold. Surface hydrophilicity and biological activity of the PLLA-HAp grafts were enhanced by fibrin coating after PRP activation. TheIn vitrocell culture studies which were carried out by using mouse pre-osteoblasts (MC3T3-E1) showed that graft materials supported by PRP increased cellular proliferation and osteogenic differentiation significantly. Thein vivoresults demonstrated that compared with bare PLLA-HAp/M grafts, the PRP loaded grafts (PRP-PLLA-HAp/M) induced significantly greater bone formation based on computed tomography, histological and immunohistochemical analyses. Our findings suggest that 3D PLLA nanofibrous matrices can be used as a graft material for irregular bone defects especially when combined with PRP as an osteogenic induction agent.
... (1,10) . However, studies by Okuda et al., Aghaloo et al. and Wiltfang et al. showed contrasting results (17,36,37) , the limited number of cases in the present work and the morphology of the IBDs could cause the conflicting results . Further, it was suggested that growth factors present in high concentrations at inappropriate times or for an extended duration can adversely affect cell behavior (1,37) . ...
... However, studies by Okuda et al., Aghaloo et al. and Wiltfang et al. showed contrasting results (17,36,37) , the limited number of cases in the present work and the morphology of the IBDs could cause the conflicting results . Further, it was suggested that growth factors present in high concentrations at inappropriate times or for an extended duration can adversely affect cell behavior (1,37) . ...
... By using a 5-mm rounger, a 5-mm bone defect was created in the central one-third of the zygomatic arch (Fig. 2B). 8,9 The periosteum at the remaining zygoma was preserved. The periosteal grafts, each about 4 Â 1.5 cm in size, were harvested from the cranium of 12 experimental animals. ...
... 25,26 Thus, we thought that a synergistic effect could be obtained by using periosteal graft combined with PRP. 3,9,27,28 In micro-CT analysis of new formed bone at 16th week, the periosteal graft þ PRP combination displayed significantly better results than control group regarding mean BV (mm 3 ) (P ¼ 0.028), and mean BMD (mm 2 ) (P ¼ 0.001). There were also significant differences between the groups regarding new bone regeneration scorings, histologically. ...
Introduction:
This study investigated the effect of periosteal graft + platelet-rich plasma (PRP) combination on facial bone defect healing.
Methods:
Five-millimeter critical sized defects in zygomatic arches of 12 adult New Zealand rabbits were created. Rabbits were randomly divided into 3 groups: First group (control group): bone defects of left zygomatic arches of 6 rabbits were wrapped with a silicone tube. Second group (periosteal graft group): bone defects of left zygomatic arches of 6 rabbits were wrapped with periosteal graft. Third group (experimental group): bone defects of right zygomatic arches of 12 rabbits were wrapped with periosteal graft-PRP combination. New bone formation was evaluated at 8th and 16th weeks. One rabbit was sacrificed at 8th week. Remaining 11 rabbits were imaged with 3-dimensional computed tomography (CT) at 16th week; then, zygomatic arches were removed for micro-CT and histologic examinations.
Results:
Three-dimensional CT analysis at 16th week revealed no significant difference between groups regarding new bone formation (P = 0.232). Micro-CT analysis of new regenerated bone at 16th week displayed significant differences between groups 1 and 3 regarding mean bone volume (BV, mm) (P = 0.028) and mean bone mineral density (BMD, mm) (P = 0.001). There was no difference between groups 2 and 3 or between groups 1 and 2, regarding BV or BMD. Histological Bone Regeneration Scorings at 16th week displayed significant difference between groups (P = 0.015). Negative correlation between 3-dimensional CT and histologic results (r = 0.120); positive correlations between BV/BMD values in micro-CT and histologic results (r = 0.524 and r = 0.456) were found.
Conclusions:
By enhancing bone formation capacity of periosteal grafts, periosteal graft-PRP combination provided bone formation having more volume and density comparing with silicone tube application.
... El volumen plaqueta- rio elevado se lo relaciona con pobres desenlaces en eventos vasculares cerebrales isquémicos, indepen- dientemente a otros parámetros; la cuenta plaque- taria se encuentra significativamente disminuida en pacientes con evento vascular cerebral isquémico con pobre pronóstico. [20][21][22] En casos de sepsis, destaca el estudio de Klinikum St. Georg (Leipzig, Alemania); en lo medular, se ana- lizaron 191 expedientes de pacientes con una edad media 72 años, diagnosticados de sepsis. Se evaluó prospectivamente el VMP al momento de la admi- sión, del diagnóstico de sepsis y durante el curso de la enfermedad; establecieron que es un marcador predictivo. ...
... Se concluyó que el mejor predictor de muerte o supervivencia es el valor discriminatorio de VMP con un valor de 8,7 fl. 20,21 En Ecuador, Vélez y colaboradores determinaron que un volumen medio plaquetario igual o mayor a 10 fl, se correlacionó con el incremento en la mortali- dad; el estudio fue realizado en pacientes críticos con sepsis de cualquier etiología. Fue llamativo además la correlación positiva entre contaje leucocitario y volumen medio plaquetario reportado en éste mis- mo estudio 45 . ...
Introducción: la sepsis es la respuesta del huésped a una infección sistémica; sus formas severas (sepsis grave y choque séptico) afectan a millones de personas en el mundo, provocando la muerte a uno de cada cuatro pacientes (campaña de sobrevida a la sepsis). Pese a los avances tecnológicos que implican nuevos fármacos, investigación molecular, biomarcadores y estrategias terapéuticas, los logros alcanzados no permiten predecir la severidad del cuadro y anticipar la mortalidad.Objetivo: validar al volumen medio plaquetario (VMP), un valor reportado rutinariamente en el hemograma como predicitor de mortalidad en pacientes sépticos.Material y métodos: se realizó un estudio prospectivo no experimental, en la unidad de terapia intensiva del hospital Pablo Arturo Suárez de Quito en el periodo julio de 2012 hasta octubre de 2014; el universo lo conforman todos los pacientes ingresados con diagnóstico de sepsis que cumplieron los criterios deinclusión. Se consideraron las variables: VMP, contaje leucocitario, sitio de la infección, edad, género y condición al egreso.Resultados: el grupo de estudio se conformó con 87 pacientes; el sitio de infección más frecuente fue a nivel abdominal, seguido de pulmón y vías urinarias. El porcentaje de supervivencia fue 63,2%, dato que coincide con la mortalidad promedio a nivel mundial. Las curva ROC (AUC: 85,4) y la correlación lineal de Pearson (contaje leucocitario–VMP) (r: 0,94), confirman la utilidad del VMP como predictor de mortalidad en casos de sepsis.Conclusión: el volumen medio plaquetario igual o mayor a 8.5 fl predice adecuadamente la mortalidad en pacientes con sepsis.
... -Platelet-derived growth factor (PDGF), -Transforming growth factor-b (TGF-b), -Insulin-like growth factor -1 (IGF-1), -Insulin-like growth factor -2 (IGF-2), -Vascular endothelial growth factor (VEGF), -Epidermal growth factor (EGF), -Fibroblast growth factor-2 (FGF-2), -Bone morphogenetic proteins (BMP), -Keratinocyte growth factor (KGF), -Interleukins (IL) [77]. Many reports [64,[77][78][79][80][81][82][83] have suggested the suitability of PRP for enhancing bone regeneration in autologous bone grafts and other bone substitutes, although others have shown no benefit of PRP on bone formation [80,[83][84][85][86][87][88][89][90][91]. ...
... -Platelet-derived growth factor (PDGF), -Transforming growth factor-b (TGF-b), -Insulin-like growth factor -1 (IGF-1), -Insulin-like growth factor -2 (IGF-2), -Vascular endothelial growth factor (VEGF), -Epidermal growth factor (EGF), -Fibroblast growth factor-2 (FGF-2), -Bone morphogenetic proteins (BMP), -Keratinocyte growth factor (KGF), -Interleukins (IL) [77]. Many reports [64,[77][78][79][80][81][82][83] have suggested the suitability of PRP for enhancing bone regeneration in autologous bone grafts and other bone substitutes, although others have shown no benefit of PRP on bone formation [80,[83][84][85][86][87][88][89][90][91]. ...
The aim of this paper is to highlight the classification and indications of different bone grafting materials and barrier membranes for everyday clinical practice of contemporary work in the field of oral surgery and periodontology. Bone resorption after tooth extraction can make the procedure of dental implantation difficult. Thus, the socket preservation concept was implemented to minimize bone resorption after tooth extraction and preserve the alveolar bone by means of different bone graft materials filled into the socket immediately after tooth extraction. Number of different growth factors are used together with graft materials. Among these are platelet rich plasma (PRP) and platelet-rich fibrin (PRF). With the simplified technique, an autologous fibrin matrix, which contains platelets and leucocyte growth factors, is acquired.
... PRP can be produced by various methods and is a source of platelet-derived growth factors (PDGFs) with angiogenic and osteoinductive potential 5,6 and cells. 7 It has been evaluated in numerous in vivo animal model studies for its potential to enhance bone healing [7][8][9][10][11] and OAC and autograft healing. 12,13 The results from these studies have been variable with some findings improving bone healing with PRP treatment and others with no significant benefits for PRP treatment with respect to bone healing. ...
... Therefore, at each time point, there was an OCA plug treated with a BMC or PRP sample from each dog. The OCAs were placed into 6-well culture plates containing 8 pyruvate, penicillin, streptomycin, and amphotericin B) and cultured for 7 or 14 days (n ¼ 6/group/day). The media were changed on days 3, 7, 11, and 14 and collected on days 3, 7, and 14 for biomarker analysis. ...
Fresh osteochondral allograft (OCA) transplantation is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Since a lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. This study sought to determine and compare the potential of bone marrow aspirate concentrate (BMC) and leukoreduced platelet rich plasma (PRP) to repopulate the osseous portion of an OCA with cells and deliver osteogenic proteins. It was hypothesized that BMC would have significantly higher colony forming units (CFUs)/mL and seed the osseous portion of OCA with more cells than PRP. Finally, we hypothesized that the media of BMC and PRP treated OCAs would have significantly higher concentrations of osteogenic proteins compared with negative control OCAs. Cylindrical OCAs (n = 36) created from tissue stored for 21 days were treated with BMC (n = 12) or PRP (n = 12) obtained for 6 dogs, or left untreated as a negative control (n = 12). After treatment, OCAs were cultured for 7 or 14 days. Media were collected for analysis of osteogenic biomarker concentration. Samples of each BMC and PRP were tested for CFU concentration. On day 7 or 14, the grafts were assessed for cell surface adhesion and penetration using fluorescent microscopy. Significant differences in CFU and media biomarker concentration the between groups were determined using one-way analysis of variance (ANOVA) and Tukey's post-hoc test with the significance set at p < 0.05. Only OCAs saturated with BMC had viable cells detectable on the osseous portion of the allografts at day 7 and 14 of culture. BMC samples had a significantly higher (p = 0.029) CFU/mL compared with PRP samples. At day 3 and/or 7 of culture, the concentration of several osteogenic proteins was significantly higher in both BMC and PRP samples. Autogenous BMC can be used to deliver both a cell population and osteogenic proteins that may improve healing of the osseous portion of the OCA clinically.
... 123,150,154,161,168,175,176,178 Notably, the dose-dependent response of PRP observed in in vitro studies was also echoed in some of the in vivo experiments. 67,190 Of the 45 pre-clinical animal studies that evaluated radiographic bone healing, 36 studies (80%) reported improvements when PRP was employed, whereas 7 studies (16%) did not reveal any radiographic improvement, and 2 studies (4%) even indicated reduced radiographic bone healing. Similarly, out of the 58 pre-clinical animal studies assessing histopathologic bone healing, 43 studies (74%) reported positive outcomes when PRP was applied. ...
Despite significant advances in the understanding and delivery of osteosynthesis, fracture non-union remains a challenging clinical problem in orthopaedic surgery. To bridge the gap, basic science characterization of fracture healing provides a platform to identify and target biological strategies to enhance fracture healing. Of immense interest, Platelet-rich plasma (PRP) is a point of care orthobiologic that has been extensively studied in bone and soft tissue healing given its relative ease of translation from the benchtop to the clinic. The aim of this narrative review is to describe and relate pre-clinical in-vitro and in-vivo findings to clinical observations investigating the efficacy of PRP to enhance bone healing for primary fracture management and non-union treatment. A particular emphasis is placed on the heterogeneity of PRP preparation techniques, composition, activation strategies, and delivery. In the context of existing data, the routine use of PRP to enhance primary fracture healing and non-union management cannot be supported. However, it is acknowledged that extensive heterogeneity of PRP treatments in clinical studies adds obscurity; ultimately, refinement (and consensus) of PRP treatments for specific clinical indications, including repetition studies are warranted.
... These are predominantly implemented to regenerate bone imperfections located in the craniofacial area [29]. To circumvent the issue of donor morbidity arising from autogenous grafts, bone substitutes can be employed [30,31]. An ideal bone graft should possess osteoconductive, osteoinductive, and osteogenic properties. ...
Promising research results have been obtained on the tissue-regeneration properties of PRF (platelet-rich fibrin) in dentistry and maxillofacial surgery. PRF presumably promotes healing and accelerates ossification. In this case report, the patient had a history of Gorlin–Goltz syndrome, also called nevoid basal cell carcinoma syndrome, an autosomal dominant neurocutaneous disease that was known for many years. As a consequence, cysts were detected in both the mandible and maxilla. We performed decompression on this 37-year-old patient, followed by a cystectomy on an extensive lesion in the right angle of the mandible. One cyst from each side of the body mandible and one from the maxilla were completely enucleated, as determined using an intraoral exploration. The resulting bone defect was filled with a composite graft composed of a mixture of A-PRF and a serum albumin-coated bone allograft (BoneAlbumin). The wound was then covered with a PRF membrane. The surgical sites were closed per primam. The postoperative period was uneventful. Biopsies were performed after three and six months of healing for histological micromorphometry analyses. Dental implants were placed at the sampling site. Three months after the implantation, the ossified implants were fitted with superstructures. To date, no complications have appeared with the bone augmentation. The authors interpret from the findings that the combination of A-PRF and BoneAlbumin can be validated as a prosperous bone substitute. It can be safely implanted after a 3-month ossification period.
... Platelet-rich plasma (PRP) has shown promise in this regard, although its use remains controversial. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] Recent histological studies showed that the combination of PRF and BG yields greater benefits during bone healing compared to BG alone in maxillary sinus augmentation. 22 In terms of treatment, there are a variety of options available for addressing the muscular aspects of postures-related temporomandibular disorders. ...
Purpose
To compare the clinical repair effects of leaving the defect empty and using Platelet-Rich Fibrin (PRF) combined with BIO-GENE artificial bone powder in patients with bone defects 6 months after jaw cystectomy.
Patients and Methods
From June 2021 to June 2022, 70 patients who were admitted to the Department of Stomatology, Affiliated Hospital of Yanbian University, and were diagnosed with jaw cysts postoperatively were selected. All of the patients were divided into two groups according to random method, among which 35 patients who underwent cystectomy alone were recorded as group A, which served as blank control; 35 patients who underwent cystectomy and PRF combined with BIO-GENE artificial bone meal repaired bone defects during the same period were recorded as group B. 3D Slicer 5.0.3 software was used to reconstruct Cone Beam Computed Tomography (CBCT) after operation. In this study, the preoperative and postoperative CBCT data of the patients were analyzed using 3D Slicer 5.0.3 software in DICOM format to calculate the cleft volume before surgery and the newly formed bone volume after surgery. The osteogenesis rate was measured based on these calculations.The bone formation percentage in the bone defect area was recorded at 6 months, and the clinical curative effects of the two groups were compared.
Results
After 6 months of surgery, the patients showed varying degrees of restoration in the jaw cyst area.The osteogenesis rate at 6 months in group A was 76.06±13.38%, while group B had a rate of 92.87±5.72%.The CBCT values in group B were higher than those in group A at 6 months post-surgery (P<0.05), t=−6.84.Group A and Group B showed a statistically significant difference.
Conclusion
Compared with simple cystectomy, PRF combined with BIO-GENE artificial bone powder has a better effect on the speed of bone repair after cystectomy within 6 months and provides more favorable effects for the repair of postoperative dentition defects, and provides support to repair teeth after defects such as dental implants.
... [23] may help to explain the differences of opinion around its use. Possible contributors to this diversity include centrifuge settings, blood collection reagents, and platelet activation protocols [24] . ...
... And in turn, a lower increase in bone temperature facilitates the collection of autologous bone during the intervention for later use. Using this technique, the bone obtained preserves a large part of its cellular vitality and can be used in peri-implant defects or gaps [12]. ...
Unlabelled:
Osseointegration is a process that depends on a multitude of factors, including the type of drilling, whether biological or conventional.
Objective:
Establish box-counting dimension values for radiological images in patients with implants placed with both drilling methods.
Material and method:
The sample included 129 implants corresponding to 50 patients. A double-blind study of data collection was carried out with the subsequent analysis of the fractal dimension as a comparative value of the state of the trabecular architecture.
Results:
We found no significant differences (p ≥ 0.05) between the two study groups comparing both drilling techniques. The values for the conventional drilling technique are 0.24 ± 0.07 and for biological drilling: 0.19 ± 0.11 with a p-value of 0.767.
Conclusions:
The drilling technique does not influence the success of the procedure and the osseointegration process.
... Therefore, researchers have extensively studied the osteoinductive and osteoconductive effects of different biological and chemical agents to accelerate this process. One such biological agent is plateletrich plasma (PRP) (20)(21)(22). There is a growing interest in applying PRP for bone repair as it reduces injured tissue's recovery time. ...
Background: Both low-level laser therapy (LLLT) and platelet-rich plasma (PRP) are demonstrated to promote the repair of mandibular defects. Objectives: This study investigated the mechanical properties and calcium content at the tooth extraction site in a rat model exposed to LLLT (λ = 808 nm) with or without PRP. Methods: In this experimental rat model study, the left first molar maxillary teeth were extracted in twenty male rats. Then, the animals were randomly divided into four groups. Group one: after extraction, the extraction sockets were treated with 0.9 W gallium-aluminum-arsenide (GaAlAs) diode laser irradiation for five minutes every 72 hours for the next 12 days (4 times overall); group two: PRP was placed in the extraction sockets; group three: a combination of both treatments (LLLT+PRP) was applied; group four: the extraction sockets remained untreated (the control group). All rats were sacrificed 30 days post-operative. All bone blocks of the extracted socket were prepared for mechanical strength and calcium content analyses. Mann-Whitney test, one-way ANOVA test, and post hoc Fisher’s least significant difference (LSD) were used to analyze the data. A P-value less than 0.05 was considered significant. All analyses were performed by SPSS 16.0. The graph is illustrated in the graph pad 5. Results: The compressive strength in the laser group was significantly higher than in the control and PRP-treated groups (P = 0.0001 and 0.00044, respectively). Compared to the control and PRP groups, the effects of a combination of PRP and LLLT mechanical strength were statistically similar. Calcium content was influenced by none of the treatments. Conclusions: The mechanical strength of the bone blocks was significantly stronger in the LLLT group than in the other groups. PRP alone or combined with LLLT demonstrated a synergistic impact on neither mechanical strength nor calcium content.
... Furthermore, the published evidence highlighted many ways of preparing PRP such that the concentrations of platelets and leukocytes can vary considerably. We noted that in some in vitro studies, LR-PRP promoted acute inflammatory responses and increased synoviocyte death [21], whereas LP-PRP stimulated chondrocytes to express type II collagen and aggrecan [22]. Notably, the double syringe system used in our study generated LP-PRP, which Noh et al. [23] reported has higher transforming growth factor beta 1 (TGF-b1) and fibroblast growth factor 2 (FGF-2) concentrations than leukocyte-rich PRP produced with the GPS III Platelet Concentration System (Zimmer Biomet, Warsaw, IN, USA). ...
Objectives:
To compare the short-term benefits and results of autologous conditioned plasma (ACP) and hyaluronic acid (HA) injection in osteochondral defects in the knee of young adults. The effectiveness of intra-articular platelet-rich plasma (PRP) injections has been evaluated in osteoarthritis. However, few studies investigated its efficacy in knee osteochondral defects.
Methods:
This is a retrospective analysis of prospectively collected data. A matched cohort of 30 patients in each group was studied. Group 1 received three HA injections at weekly intervals, and group 2 received three ACP injections at two weekly intervals. We measured Kujala, Lysholm, Oxford, and visual analog scale (VAS) scores at baseline, six, 12, and 36 months to assess function and pain.
Results:
Most lesions were in the medial femoral condyles in both groups, followed by lateral femoral condyle and patellofemoral regions. In group 1 (HA), the mean pre-injection scores for Kujala, Lysholm, and Oxford improved significantly at six and 12 months. The scores decreased at 36 months, however, they remained significantly better than the baselines (P < 0.05). The pre-injection VAS scores continued to improve significantly from 6.06±0.785 to 3.40±0.912 at 36 weeks. In group 2 (ACP), VAS and the outcome scores showed a consistent and statistically significant improvement from pre-injection to 36 months. Conclusions: Our study confirms the short-term clinical benefits of using ACP for symptomatic osteochondral defects of the knee. Further high-quality comparative studies with longer follow-ups are needed to ascertain whether ACP is beneficial in the long term.
... Therefore, researchers also study the osteoinductive and osteoconductive in uence of different biological and chemical agents to accelerate this process. One of these biological agents is platelet-rich plasma (PRP) [19][20][21]. The growing interest in using PRP for bone repair is due to a reduction in the recovery time of injured tissue. ...
Background: Both low-level laser therapy (LLLT) and platelet-rich plasma (PRP) have been suggested to improve the repair of mandibular defects. This study investigated the mechanical properties and calcium content at the tooth extraction site in the rat model exposed to LLLT (λ=808 nm) with or without PRP.
Methods: In this experimental rat model, the maxillary left first molar teeth were extracted in twenty male rats. Then, they were divided randomly into four groups. Group one: the extraction sockets were treated by 0.9 W gallium-aluminum-arsenide (GaAlAs) diode laser irradiation for five minutes every 72 hours after extraction for the next 12 days (4 times in overall); group two: PRP was placed in the extraction sockets; group three: a combination of both treatments (LLLT+PRP) was done; group four: untreated extraction socket as the control group. All rats were sacrificed 30 days post-operative. All bone blocks of the extracted socket were prepared for mechanical strength and calcium content analyses.
Results: The compressive strength in the laser group was significantly higher than in both the control and PRP-treated groups (p=0.0001 and 0.00044, respectively). Although a combination of both PRP and LLLT elevated the mechanical strength compared to the control and PRP groups, it was statistically similar to LLLT/PRP group. Calcium content did not change by any of the treatments.
Conclusions: Mechanical and chemical analyses on the bone blocks demonstrated that LLLT improved bone healing; however, PRP alone or combined with LLLT did not show a synergistic impact.
... Only autogenous bone grafts have osteogenic capacity. Osteoinductive bone graft stimulates host mesenchymal cells to differentiate and begin bone formation by transfer of proteins which 8 provide a signalling cascade from the host to form bone. Osteoconductive bone grafts just provide a scaffold to create new bone. Bone healing can be primary and secondary. ...
BACKGROUND: Odontogenic cysts with large bony defects have always been the drawback for conservative management of these lesions. The healing of bony defects with bone regeneration of bone in cystic cavities has always been a challenging task. Various bone substitutes have been used to accelerate bone formation in cystic cavities. The greatest drawback of alloplasts is lack of osteogenic or osteoconductive property. This has led to a severe attempt to improve the physical properties of alloplastic materials by combining molecular, cellular and genetic tissue engineering technologies and one such attempt is platelet rich fibrin(PRF). The purpose of this study is to assess the healing of bone defects following cyst enucleation when osteoconductive alloplasts are combined with PRF. MATERIALS AND METHODS: This single group randomized interventional study was done on 20 patients (14 male and 6 female) in the age group of 18 to 50 years. Patients with Mandibular or Maxillary odontogenic cysts with radiographic radiolucency measuring upto 5 cm in any of the three dimensions, and who were willing for a regular follow up were included. The enucleated cystic bony cavities were filled with autogenous PRF and alloplastic bone graft material. The patients were followed up for a period of two years. The bone formation in the cystic cavity was assessed preoperatively and post operatively using Orthopantomogram (OPG). The density of the bone formed post operatively was assessed using Computed Tomography (CT) scan after 6 months and was compared with the normal bone on the opposite side in Hounsefield units(HU). Infection and wound dehiscence were also assessed. RESULTS AND CONCLUSIONS: The mean age group of the patients were 29.9 ± 8.15 years. 60% of the odontogenic cysts were found in the anterior region from canine to canine. Histopathologic diagnosis of treated cysts revealed 70% were radicular cysts and 30% were dentigerous cysts. The average dimensions of the cyst measured from the CT scan was: supero inferiorly 1.17 ± 0.41 cm, antero posteriorly 1.495 ± 0.86 cm, and medio lateral dimension 2.17 ± 0.75 cm. The average bone density in the cystic cavity filled with bone graft mixed with autogenous PRF achieved after six months was 374.35 ± 38.786 HU which was significantly higher than the average bone density on the contra lateral side (normal bone) which was 315.279 ± 43.476 HU.
... Previous http://annalsofrscb.ro histologic studieshave shown that β -TCP particles are resorbed in 12 -24 months and replaced with the newly generated bone in 36 months. Wiltfang et al. 24 compared the graft materials with PRP in pigs and they observed β -TCP particles remaining in the bone defects at 12 th week. At the end of the 12th week of the study by Yilmaz et al 25 , β-TCP particles were observed histologically in the cavities that contained β -TCP alone, but no β -TCP particles were observed in the bone marrow when β -TCP and PRF has been used in combination. ...
The aim of this study was to evaluate and compare the clinical and radiographic outcomes of intrabony defects accessed with a Single Flap Approach, with an occlusive Platelet Rich Fibrin membrane, that did or did not receive an additional Hydroxyapatite -Beta Tri Calcium Phosphate composite bone graft.
The study comprised 30 patients presenting with intra-bony defects who were randomly treated using Single Flap Approach with Platelet Rich Fibrin and with or without additional bone graft (Hydroxyapatite + β Tri Calcium Phosphate composite graft). Patients were recalled at 12 and 36 months to assess and compare the Full Mouth Plaque scores (FMPS%), Full mouth bleeding scores (FMBS%),Probing Pocket Depth (PPD), Relative Clinical Attachment Level (R-CAL),position of Gingival Margin at surgical site (GM), and Radiographic assessment of crestal bone level with Radiovisiography - RVG (mm).
The results revealed a significant reduction in the mean FMPS%, FMBS%, & PPD within the groups (p≤0.0001),but did not reveal any statistical significance when compared between the test and the control groups at various time points (12 and 36 months). Both test and control groups showed statistically significant gain in the mean Relative Clinical Attachment Levels (R-CAL) at 12 months (p≤0.0001). The position of the gingival margin (GM) had a minimal gradual apical shift (gingival recession) till 12 months with a mild statistical significance of (p≤ 0.048) in the control group. The test group initially had a coronal shift at 12 months’ time point and then shifted apically later and became comparable at 36 months between the control and the test group but with no statistical significance(p≤0.784).RVG values revealed a statistically significant radiographic bone fill (p≤0.0001) in both, test group and the control group at 12 months’ time point. This Bone fill significantly improved in both the groups when measured at 36 months, and the test group had a better bone fill compared to the control group with statistical significance (p≤0.023).
The results of this study indicate that the sites which received PRF alone and PRF + HA -βTCP in the treatment of periodontal intraosseous defects accessed with Single Flap A were clinically effective with a substantial probing pocket depth reduction and clinical attachment gain. Although the adjunctive use of HA -βTCP graft shows a significant bone fill radiographically under the experimental conditions it offers no significant adjunctive effects on the surrogate markers.
... Despite this, it would be interesting to delve into these modifications made to the original technique, leading to the establishment of protocols based on the evidence studied in the short, medium, and long term. The clinical importance of drilling at low revolutions is that the bone partially retains vitality and can be used alone or mixed with biomaterials in areas where guided bone regeneration or bone preservation is required, and could also be used to correct peri-implant defects or fill the space between bone and implant (11) . ...
Osseointegrated implants are currently the prosthetic treatment by predilection in the oral cavity when dental organs have been lost. Bone deficiency interferes with the placement of these prosthetic attachments; To solve this lack of bone tissue in alveolar ridges, autologous, homologous or heterologous bone grafting techniques are proposed. The ultra-low speed drilling without irrigation, it is possible to collect autologous bone at the time of preparing the surgical site before placing the dental implant, which provides the best properties for bone regeneration without the need for another wound or more morbidity for the patient. We describe our ultra-low speed drilling protocol step by step, obtaining autologous bone from the same surgical site to rehabilitate small bone defects around the implant reducing comorbidities and surgical times.
... When considering the overall combined impact of PPP and PRP irrespective of the time interval, an obvious increase in BIC% was observed with more than 60% in both test groups. Our findings were in an agreement with some studies [32,42,43]; at the same instance, inconsistencies were observed with other studies suggesting no influence of PPP or PRP on new bone formation [44][45][46]. The possible explanation for the inconsistent findings could be due to the different centrifugation techniques which can lead to substantial difference in platelet, leucocyte, and growth factors level. ...
Abstract Background Bone-to-implant contact ratio (BIC%) plays a critical role in secondary stability of osseointegrated dental implants. The aim of this study was to identify the correlation of 2D/3D micro-CT images with histology as a gold standard for evaluating BIC% and to investigate the influence of the platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on 3D BIC% following delayed implant placement with delayed loading (DIP+DL). Methods Nine beagle dogs were recruited. Following bilateral extraction of mandibular 3rd premolar, 4th premolar, and 1st molar, 54 screw-type titanium implants were inserted and randomly divided into one control and two test groups based on a split-mouth design. The control group involved DIP+DL (n = 18) and both test groups included DIP+DL with local application of PRP (n = 18) and PPP (n = 18). A BIC analysis was performed utilizing 2D histomorphometry and 2D/3D micro-CT. Following identification of correlation between histology and 2D/3D micro-CT images, a 3D micro-CT assessment of the 3D BIC% at three follow-up time-points (1, 3, and 6 months) was carried out for observing the influence of PRP and PPP on BIC. Results The 2D micro-CT BIC% values revealed a strong positive correlation with histology (r = 0.98, p
... The preparation method of the PRP can signicantly inuence the concentrations of platelets and growth factors, 47 and consequently their osteogenic capacity. 48 The current study 50 Notably, different kinds of seed cells may show discrepant responses to PRP stimulation. Xie et al. observed that same PRP gel exerted stronger pro-proliferative effects on bone marrow MSCs than adipose tissue-derived MSCs. ...
A new highly controlled powder sintering technique was used for the fabrication of a porous Ti6Al4V scaffold. The platelet-rich plasma (PRP) was prepared using whole blood. The PRP was used as a cell carrier to inject bone marrow mesenchymal stem cells (MSC) into the pores of the Ti6Al4V scaffold in the presence of calcium chloride and thrombin, and then the composite construct of porous Ti6Al4V loaded with PRP gel and MSC was obtained. The bare Ti6Al4V scaffold and the Ti6Al4V scaffold loaded with MSC were used as controls. The characteristics and mechanical properties of the scaffold, and the biological properties of the constructs were evaluated by a series of in vitro and in vivo experiments. The results show that the sintered porous Ti6Al4V has good biocompatibility, and high porosity and large pore size, which can provide sufficient space and sufficient mechanical support for the growth of cells and bones without an obvious stress shielding effect. However, Ti6Al4V/MSC/PRP showed a significantly higher cell proliferation rate, faster bone growth speed, more bone ingrowth, and higher interfacial strength. Therefore, the porous Ti6Al4V scaffolds incorporated with MSC and PRP may be more effective at enhancing bone regeneration, and is expected to be used for bone defect repair.
... In the future, we will make a study on the effect of trehalose induced into intracellular space of MSCs through transporter Vector (TRET1). by osteoconduction and osteoinduction (Wiltfang et al. 2004;Misch 2010). But to avoid the unfavorable condition of donor morbidity, it is better to use bone substitutes. ...
Voltammetry techniques such as cyclic voltammetry and electrochemical impedance spectroscopy are used to quantify metal ions in aqueous solutions. In this paper, we have reported electrochemical detection of lead (II), cadmium (II), and Copper (II) ions based on carbon paste electrode using graphite powder. Potassium ferricyanideK3 [Fe(CN)6] solutions as benchmark media to check redox reactions. The Detection limit was 6.56 × 10–9 M investigated by cyclic voltammetry. Effects of pH and supporting electrolytes were also measured.
... активація інших факторів росту призводить до індукування функцій фібробластів і остеобластів, пришвидшує диференціацію клітин, а також впливає на функції інших клітин, наприклад макрофагів. Крім того, існують докази того, що PDGF збільшує швидкість проліферації стовбурових клітин [14]. ...
Резюме. Відомо, що використання власної крові для лікування різних захворювань почалося в стародавні часи з моменту зародження медицини. На даний момент застосування збагаченої тромбоцитами плазми (ЗТП) є одним з успішних напрямків тканинної інженерії і клітинної терапії у медицині. В еволюції термінології буває безліч різних варіантів назв збагаченої тромбоцитами плазми як кінцевого продукту. В клінічній практиці вважають, що стимулювальний ефект її можливий при концентрації тромбоцитів у ній не менше 1000 000/мкл. При ушкодженні тканин тромбоцити відіграють провідну роль у загоєнні й регенерації тканин завдяки вивільненню факторів росту. На основі відомостей у фаховій літературі показано високий потенціал терапії збагаченою тромбоцитами плазмою для регенерації кісткової тканини. Досі не виконали належних клінічних досліджень щодо ефективності терапії збагаченою тромбоцитами плазмою, які відповідали б усім сучасним критеріям. Терапія збагаченою тромбоцитами плазмою є перспективною галуззю в медицині та потребує наступних досліджень як новий ефективний і безпечний метод у лікарські практиці. Мета дослідження – проаналізувати наукову літературу щодо ефективності застосування аутологічної плазми, збагаченої тромбоцитами, для оптимізації лікування стоматологічних захворювань. Матеріали і методи. У дослідженні застосовано бібліосемантичний та аналітичний методи дослідження. Результати досліджень та їх обговорення. Під час виконання дослідження було проведено огляд та аналіз останніх даних вітчизняної та зарубіжної науково-медичних літератур щодо сучасних аспектів застосування аутологічної, збагаченої тромбоцитами плазми, при лікуванні стоматологічних захворювань, огляд основних методик для її виготовлення, переваги та недоліки її застосування. Висновки. На основі проведеного аналізу доступної літератури ми зробили висновок про збереження значної актуальності удосконалення підходів щодо лікування основних стоматологічних захворювань збагаченою тромбоцитами плазмою. Тому питання сучасного застосування в стоматології аутологічної, збагаченої тромбоцитами плазми, залишаються актуальним і потребує подальшого вивчення.
... Sin embargo los hematíes, glóbulos rojos o eritrocitos, ya eran conocidos desde el tiempo de van Leeuwenhoek, Schultze fue él primero en publicar una descripción de las plaquetas. Él describió "esférulas" mucho más pequeñas que los eritrocitos que ocasionalmente se agrupaban y participaban en colecciones de fibrina, recomendó estudios adicionales sobre estos hallazgos(21)(22)(23) Giulio Bizzozero (1846-1901), aportó sobre los reportes de Schultze, usó "circulación en vivo" para estudiar las células sanguíneas de batracios y anfibios microscópicamente. Él notó que las plaquetas se agrupaban en el sitio de la lesión vascular, un proceso que se anticipaba a la formación del coágulo. ...
Mean platelet volume is the geometrical measure of the platelets size and has an inverse relationship with the number of these, it's also an indicator of platelet activation. There isn't a stablished cut-off point because the values are constantly changing and varies from population to population according to the technique used and testing time; However, it is established that values higher than 9.5 femtoliter (fL) correlate with diseases that have inflammation, endothelial dysfunction, and a prothrombotic state as a substrate. Evidence shows that increased mean platelet volume correlates with poor prognosis in patients with metabolic syndrome, diabetes mellitus, cardiovascular disease, sepsis, pulmonary embolism and immuno-inflammatory diseases.
In our study we want to check that in septic processes of any etiology, an increased mean platelet volume is correlated with unfavorable prognosis of life.
XVI
The results demonstrated that the mean platelet volume is adequate predictor of poor prognosis and mortality in septic patients with a cutoff of 8,5 FL. demonstrated a direct proportionality between mean platelet volume and leukocyte count. No correlation was found with other variables such as age, gender and infection site.
... Platelets are derived from blood megakaryocytes in bone marrow and then are divided into inactive cells and active cells. PRP releases many growth factors such as PDGF, IGF-1, and TGF-β1 [20][21][22]. Wiltfang et al. have evaluated the effects of PRP on the regeneration of bony defects in the forehead area in mini-pigs [23]. Twelve weeks postsurgery, the results demonstrated a dramatic effect of (MAS) could be implanted into bone defects and attract colonizing MSCs from the native bone tissue of the host [26]. ...
Platelet-rich plasma (PRP) has been shown to be a beneficial growth factor for bone tissue healing and is used in implantology. The aim of this study was to investigate the effects of PRP on bone defects in rabbits. Twenty rabbits were used to establish the implant bone defect model in this study. An intrabony defect (5mm × 5mm × 3mm) was created in alveolar bone in the lower jar of each rabbit. The wound was treated with PRP. The expression of platelet-derived growth factor BB (PDGFBB) was assessed by enzyme-linked immunosorbent assay (ELISA). Focal adhesion kinase (FAK) and related phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) levels were measured by Western blot. The results show that PRP could significantly improve the bone healing process when compared with control, and 10% PRP could markedly increase fibroblast proliferation 48-h post treatment. PDGFBB was higher in the PRP group than that in the control group. PRP treatment also could elevate the phosphorylation of FAK and PI3K/AKT, although the inhibitor of PDGFR could reverse this trend. These results suggest that PRP treatment improves the bone healing process through the FAK/PI3K/AKT pathway.
... PRP could release many growth factors, such as PDGF, IGF-1 and TGF-β1 [16][17][18]. Wiltfanng et al. has evaluated the effects of PRP on the regeneration of bony defects in the forehead area in minipigs [19]. Twelve weeks post-surgery, the results demonstrated a dramatical effect of bone regeneration in the autogenous group when animals treated with PRP. ...
Objective: Platelet-Rich Plasma (PRP) has been shown to be a beneficial growth factor for bone tissue healing and used in implantology. The aim of this study was to investigate the effects of PRP in bone defects in rabbits. Methods: Twenty rabbits were used to establish the implant bone defects model in this study. An intrabony defect (5 mm × 5 mm × 3 mm) was created in alveolar bone of lower jar of each rabbit. The wound was treated with PRP. The expression of Platelet-Derived Growth Factor BB (PDGFBB) was assessed by Enzyme-Linked Immunosorbent Assay (ELISA). The Focal Adhesion Kinase (FAK) and related Phosphatidylinositol 3-Kinase (PI3K)/AKT (protein kinase B) were measured by Western blot. Results: The results showed that PRP could significantly improve the bone healing process when compared with control, meanwhile 10% PRP could markedly increase fibroblast 48 h post treatment. PDGFBB was higher in PRP group than that in control group. PRP treatment also could elevate the phosphorylation of FAK and PI3K/AKT, however the inhibitor of PDGFR could reverse this trend. Conclusion: The results suggested PRP treatment improves the bone healing process through the FAK/ PI3K/AKT pathway.
... 1 In cases where the spontaneous healing of bones is oen insufficient, reconstruction using natural or articial gras is necessary. 2,3 Today, plenty of bone graing methods exist, with autologous bone widely used. However, there remain some drawbacks such as the risk of disease transmission, limited integration of the gra and complex storage conditions. ...
Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. The current study delivers a three-dimensional (3D) scaffold prepared by blend centrifugal spinning loaded with the osteogenic supplements (OS) β-glycerol phosphate, ascorbate-2-phosphate and dexamethasone. The OS were successfully encapsulated into a fibrous scaffold and showed sustained release for 30 days. Furthermore, biological testing showed the osteoinductive properties of the scaffolds on a model of human mesenchymal stem cells and stimulatory effect on a model of osteoblasts. The osteoinductive properties were further proved in vivo in critical size defects of rabbits. The amount of bone trabecules was bigger compared to control fibers without OS. The results indicate that due to its long-term drug releasing properties, single step fabrication process and 3D structure, the system shows ideal properties for use as a cell-free bone implant in tissue-engineering.
... As a result, resorption of a synthetic material used to fill the defect is not counterbalanced by the synthesis of the new bone, which may eventually lead to pathological fractures or nonintegration in the vicinity of the graft [22]. Consequently, synthetic reconstructive materials should be applied together with osteoinductive/osteogenic materials, such as platelet-rich plasma (PRP) and its derivatives (PRGF, plasma-rich growth factors; PRF, platelet-rich fibrin) or mesenchymal stem cells derived from bone marrow/connective/adipose/dental tissues [23][24][25][26][27]. Several animal and human studies demonstrated that bone marrow/adipose/dental-derived mesenchymal stem cells/PRF promote bone growth, due to the ability of mesenchymal cells to transform into osteoblasts or under the influence of growth factors released from platelets that may stimulate processes responsible for bone healing (e.g., mitogenesis, chemotaxis, and cell differentiation) [23][24][25][28][29][30][31]. Both PRP and its derivatives/mesenchymal cells are currently widely used as a stimulator of bone healing during reconstructive procedures in maxillofacial surgery [23][24][25][32][33][34]. ...
The aim of this study was to verify whether L-lactide/DL-lactide copolymer 80/20 (PLDLLA) and platelet-rich plasma (PRP) trigger bone formation within critical-sized calvarial defects in adult sheep ( n=6 ). Two craniectomies, each ca. 3 cm in diameter, were created in each animal. The first craniectomy was protected with an inner polylactide membrane, filled with PRP-polylactide granules, and covered with outer polylactide membrane. The second control craniectomy was left untreated. The animals were euthanized at 6, 7, 17, 19, 33, and 34 weeks after surgery, and the quality and the rate of reossification were assessed histomorphometrically and microtomographically. The study demonstrated that application of implants made of PLDLLA 80/20 combined with an osteopromotive substance (e.g., PRP) may promote bone healing in large calvarial defect in sheep. These promising proof-of-concept studies need to be verified in the future on a larger cohort of animals and over a longer period of time in order to draw definitive conclusions.
... The same findings were seen in other studies [38][39][40][41]. The trabecular bone maturation (from woven bone to lamellar bone) was seen in all tested groups; however, the amount of lamellar bone was significantly greater in the Gen-Ox + PRP group than the other; this could be attributed to the combined effect of bone morphogenic proteins present in Gen-Ox bovine organic bone matrix and the growth factors release from the platelet concentrate that stimulate bone formation such as PDGF, IGF, and VEGF [11,12], since PDGF induces the proliferation of mesenchymal cells, angiogenesis and macrophage recruitment which are crucial for bone regeneration [42]. Marx et al. [14] observed the same finding when PRP was used in combination with autogenous bone graft, and they suggested that such combination could increase the rate of osteogenesis and qualitatively enhance bone formation. ...
Abstract
Objectives This study was carried out to histologically assess
the effect of bone grafting materials extracted from
bovine origin on the bone healing process either alone or
when mixed with autologous platelet-rich plasma which
could be used in many procedures of oral and maxillofacial
bone and implant reconstructive surgery.
Materials and methods Sixteen rabbits were used; three
intrabony defects in the femur bone of each rabbit were created,
one left unfilled for normal healing process and served as
control, the second filled with xenogenic graft (Gen-Ox-lyophilized
bovine bone organic matrix), and the third filled with
(Gen-Ox-lyophilized bovine bone organic matrix) mixed with
autologous platelet-rich plasma . Histological examination of
the sections was performed after staining with H&E and Van
Geison stains. The histomorphometric analysis including
counting of bone cells (osteoblasts, osteocytes, and osteoclasts)
with performance of osteon diameter and lamellar thickness at
the end of the fourth week postoperatively was obtained.
Results It has been shown that with the use of autologous
platelet-rich plasma in combination with the xenogenic bone
graft prepared from bovine origin, new bone formation and
neovascularization were enhanced significantly when compared
with xenogenic graft alone.
Conclusion The addition of PRP to xenogenic bone substitute
in small bone defects of the rabbit femur showed a histomorphometric
increase in bone formation (at the fourth week of healing).
Clinical relevance Platelet concentrate might be used to
accelerate the osseointegration of enosseous dental implants.
Keywords Bone grafting . Platelet-rich plasma .
Histomorphometry . Gen-Ox bovine bone organic matrix
... The same findings were seen in other studies [38][39][40][41]. The trabecular bone maturation (from woven bone to lamellar bone) was seen in all tested groups; however, the amount of lamellar bone was significantly greater in the Gen-Ox + PRP group than the other; this could be attributed to the combined effect of bone morphogenic proteins present in Gen-Ox bovine organic bone matrix and the growth factors release from the platelet concentrate that stimulate bone formation such as PDGF, IGF, and VEGF [11,12], since PDGF induces the proliferation of mesenchymal cells, angiogenesis and macrophage recruitment which are crucial for bone regeneration [42]. Marx et al. [14] observed the same finding when PRP was used in combination with autogenous bone graft, and they suggested that such combination could increase the rate of osteogenesis and qualitatively enhance bone formation. ...
... This result strongly suggested that growth factors released from platelets in the PRP function to promote bone formation in the presence of rhBMP-2, as evidenced by the low numbers of platelets in BM compared to PRP. Although the exact effect of PRP on osteogenesis remains controversial, several studies have shown that PRP does not positively affect early stage bone regeneration [34,35]. However, in our previous study, we found that remarkable bone formation from an early stage was induced in the presence of both PRP and an optimal dose of rhBMP-2 [16]. ...
Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and platelets, has recently attracted the attention of clinicians as a new optional means for bone engineering. We previously reported that the osteoinductive effect of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co-transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This study aims to investigate whether BMC can effectively promote bone formation induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP-2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an automated blood separator. The BMC was then seeded onto β-TCP granules pre-adsorbed with a suboptimal-dose (minimum concentration to induce bone formation at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the induction of ectopic bone formation was assessed 2 and 4 weeks post-transplantation. Transplantations of five other groups [PB, PRP, platelet-poor plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as experimental controls. Then, to clarify the effects on vertical bone augmentation, specimens from the six groups were transplanted for on-lay placement on the craniums of mice. The results indicated that BMC, which contained an approximately 2.5-fold increase in the number of MNCs compared to PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation. On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites far from the calvarial bone. In conclusion, the addition of BMC could reduce the amount of rhBMP-2 by one-half via its synergistic effect on early-phase osteoinduction. We propose here that BMC transplantation facilitates the clinical use of rhBMP-2 as an alternative strategy for bone engineering.
... Some research workers have reported that it improved bony regeneration, and there have been other reports that disagreed. 126 Its role in craniofacial bony regeneration needs to be explored further. ...
Repair of critical-size defects caused by trauma, removal of a tumour, or congenital abnormalities is a challenge in the craniomaxillofacial region because of the limitations associated with treatment. We have reviewed research papers and updated information relevant to the various types of macroporous scaffolds. We have included papers on several biomaterials and their use in various craniofacial defects such as mandibular, calvarial, and others, as well as the latest technological developments such as 3-dimensional printed scaffolds. We selected all papers about scaffolds, stem cells, and growth factors for review. Initial selection was by review of titles and abstracts, and the full texts of potentially suitable articles were then assessed. Methods of tissue engineering for repair of critical-size defects in the craniofacial bones seem to be viable options for surgical treatment in the future. Macroporous scaffolds with interconnected pores are of great value in regeneration of bone in the craniofacial region. In recent years, various natural or synthetic materials, or both, have been developed, on which macroporous scaffolds can be based. In this review we present a review on the various types of three-dimensional macroporous scaffolds that have been developed in recent years, and evaluate their potential for regeneration of craniofacial bone.
... Положительный эффект PRP на процесс восстановления костной ткани особенно выражен на ранних сроках регенерации (4-6 недель) [46], на поздних этапах влияние PRP нивелируется [58,59]. Кроме того, сочетание PRP с мезенхимальными стволовыми клетками, костными трансплантатами [60][61][62] или искусственными подложками [24] представляет собой особый интерес для изучения оптимизации регенерации дефектов кости критического размера. Это направление исследований остается актуальным и нуждается в дальнейшей разработке, т. к. расхождения полученных результатов затрудняет их полноценную и объективную интерпретацию. ...
Вопрос регенерации костной ткани останется актуальным даже при активном развитии биотехнологий. Использование обогащенной тромбоцитами плазмы (Platelet-Rich Plasma — PRP) для оптимизации остеорепарации — одно из перспективных направлений в современной медицине.Цель: провести сравнительный анализ, обобщить и систематизировать результаты исследований, посвященных классификации, методам получения и возможности применения обогащенной тромбоцитами плазмы в эксперименте на животных, а также в клинических условиях.Методы: проанализированы публикации за последние 20 лет из электронных баз PubMed, Medline, тезисы, статьи, авторефераты, диссертации и другие релевантные источники научно-медицинской информации. Найдено более 200 работ.Результаты: на основе полученной информации освещены такие вопросы: получение и классификация PRP, исследование влияния PRP на клетки in vitro, а также возможность сочетания PRP с биоматериалами в экспериментах на животных. Кроме того, рассмотрена возможность использование PRP для восстановления костной ткани в клинике in vivo. Установлено, что использование обогащенной тромбоцитами плазмы является одним из перспективных современных методов оптимизации регенерации кости. Безопасность, эффективность и экономическая целесообразность применения PRP достаточно широко освещены в научной литературе. Однако основным недостатком PRP являются низкие прочностные характеристики, относящиеся к очень важным параметрам в случае использования для заполнения дефектов кости, особенно критического размера, при остеотомии и хирургическом лечении онкологических пациентов. В связи с этим особый интерес имеет комбинация PRP с остеопластическими материалами, мезенхимальними клетками и факторами роста. Однако существует много противоречивых моментов, которые требуют дополнительных исследований для создания трансплантата со свойствами, максимально приближенными к биологическим характеристикам кости.
... GFs present in PRP have shown to induce proliferation and differentiation of MSCs, and therefore increase the regeneration power (Witfang et al., 2004). Even if there are unmatched data in the literature concerning the effects of PRP on MSCs, most of the research shows that PRP increases and stimulates the proliferation, as well as the differentiation, of MSCs. ...
Platelet-rich plasma (PRP) is a concentrated form of autologous platelets, releasing various growth factors (GFs) when activated. The activated form usually releases a number of growth factors and cytokines in physiologically relevant ratios, although in concentrations several times higher than that of normal blood that is critical to tissue regeneration. The PRP growth factors include platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF). It is believed that these high concentrations of growth factors have significant effects on the regeneration of bone, tendon, skin, and cartilage including cell proliferation, differentiation, and improved synthesis of extracellular matrix (ECM). On the other hand, PRP can be an inexpensive and immunologically safe source of various GFs delivery. However, the efficacy of PRP for tissue regeneration is usually problematic due to its rapid inactivation and the initial burst release of GFs. Consequently, an appropriate delivery system is required for local sustained release of GFs from active-state PRP to stimulate proliferation, synthesize ECM and so on. Incorporation of PRP into nanostructures is an alternative approach for having control over sustained release of growth factors. In the present study, some proposed methodologies to load PRP and GFs into nanostructures, such as exploiting heparin conjugated nanospheres, electrospun nanofibers, graphene (oxide) and nanoliposomes are discussed comprehensively.
... Therefore, PRP has been used to induce the proliferation and differentiation of MSCs because of its high concentration of growth factors and consequently can increase the capacity of these cells for tissue regeneration. 80 In addition to the positive effects on MSCs proliferation, differentiation and migration, PRP may also provide a three-dimensional substrate for cell seeding by virtue of the presence of fibrinogen, which readily gives rise to fibrin gel upon thrombin or calcium activation. 81 ...
p class="abstract">Musculoskeletal medicine targets both cartilage regeneration and healing of soft tissues. Articular cartilage repair and regeneration is primarily considered to be due to its poor regenerative properties. Cartilage defects due to joint injury, aging, or osteoarthritis have low self-repair ability thus they are most often irreversible as well as being a major cause of joint pain and chronic disability. Unfortunately, current methods do not seamlessly restore hyaline cartilage and may lead to the formation of fibro- or continue hypertrophic cartilage. Deficiency of efficient modalities of therapy has invited research to combine stem cells, scaffold materials and environmental factors through tissue engineering. Articular cartilage tissue engineering aims to repair, regenerate, and hence improve the function of injured or diseased cartilage. This holds great potential and has evoked intense interest in improving cartilage therapy. Platelet-rich plasma (PRP) and/or stem cells may be influential for tissue repair as well as cartilage regenerative processes. A great promise to advance current cartilage therapies toward achieving a consistently successful modality has been held for addressing cartilage afflictions. The use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology may be the best way to reach this objective via tissue engineering. A current and emergent approach in the field of cartilage tissue engineering is explained in this review for specific application. In the future, the development of new strategies using stem cells seeded in scaffolds and the culture medium supplemented with growth factors could improve the quality of the newly formed cartilage . </p
Autologous fat transplantation -i.e., lipofilling- has become a promising and popular technique in aesthetic and reconstructive surgery with several application such as breast reconstruction, facial and hand rejuvenation. However, the use of this technology is still limited due to an unpredictable and low graft survival rate (which ranges from 25%-80%). A systematic literature review was performed by thoroughly searching 12 terms using the PubMed database. The objective of this study is to present the current evidence for the efficacy of adjuvant regenerative strategies and cellular factors, which have been tested to improve fat graft retention. We present the main results (fat retention rate, histological analysis for pre-clinical studies and satisfaction/ complication for clinical studies) obtained from the studies of the three main fat grafting enrichment techniques: platelet-rich plasma (PRP), the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) and discuss the promising role of recent angiogenic cell enrichment that could induce early vascularization of fat graft. All in all, adding stem or progenitor cells to autologous fat transplantation might become a new concept in lipofilling. New preclinical models should be used to find mechanisms able to increase fat retention, assure safety and transfer these technologies to a good manufacturing practice (GMP) compliant facility, to manufacture an advanced therapy medicinal product (ATMP).
Graphical Abstract
Objective: This study was designed to investigate the optimal combination of known osteogenic biomaterials with shape conforming struts to achieve calvarial vault reconstruction, using a canine model. Methods: Eighteen adolescent beagles were divided equally into 6 groups. A critical size defect of 6 x 2 cm traversed the sagittal suture. The biomaterials used for calvarial reconstruction were demineralised perforated bone matrix (DBM), recombinant human bone morphogenetic protein-2 (rhBMP2) and autogenous platelet-rich plasma (PRP). The struts used were cobalt chrome (metal) or resorbable plate. The groupings were as follows: 1) DBM + metal, 2) DBM + PRP + metal, 3) DBM + PRP + resorbable plate, 4) DBM + rhBMP2 + metal, 5) DBM + rhBMP2 + PRP + metal, and 6) DBM + rhBMP2 + resorbable plate. Animals were euthanised at 3 months post-surgery. There was no mortality or major complications. Analysis was performed macroscopically, histologically, and with computed tomography (CT). Results: There was complete bony regeneration in the rhBMP2 groups only. Non-rhBMP2 groups had minimal bony ingrowth from the defect edges and on the dural surface, a finding confirmed by CT scan and histology. PRP did not enhance bone regeneration. Shape conformation was good with both metal and resorbable plate. Conclusion: rhBMP2 but not PRP accelerated calvarial regeneration in 3 months. The DBM in the rhBMP2 groups were substituted by new trabecular bone. Shape molding was good with both metal and resorbable plate. Key words: Critical size calvarial defect, Cranial vault reconstruction, Metal struts, Resorbable plates, rhBMP2
Over the past few decades, more and more articles about platelet-rich plasma (PRP) use in regenerative medicine have been published. The aim of this study was to determine which articles have been most influential in this field by identifying and analyzing the characteristics of the 100 most cited articles. Articles on the use of PRP in regenerative medicine were identified via the Thomson ISI Web of Science database. A majority of the articles originated from the USA (36%). The top journal in terms of number of articles was American Journal of Sports Medicine (12%). Musculoskeletal system and orthopedics (54%) were the most popular fields of applications. Preclinical studies were the most represented study type, from which only 8 from 46 (17.4%) provided a complete numerical description of the injected product. Analysis showed a time-dependent trend of increasing quality of the clinical studies (p = 0.004), although none of them provided a complete biological characterization of the injected PRP. This study demonstrated that the use of PRP in regenerative medicine is a growing and popular area of research, mainly focused on orthopedic applications. Studies on PRP-derived exosomes, biological characterization, and correlation with clinical results might be areas of future trends.
Objective
In the microenvironment of wound sites, naturally occurring growth factors are crucial for cell migration, opsonisation, chemotaxis, differentiation and angiogenesis. Exogenous growth factors, such as platelet-rich plasma (PRP) and adipose tissue, also improve healing.
Method
In the present within-subject study, we described the effects of PRP and adipose tissue extract (ATE) on skin graft donor site wound healing in patients requiring split-thickness skin grafts. Each patient, having at least two donor sites, received both control (no growth factor) and experimental (PRP or ATE) treatments. Wounds were evaluated on days 5, 7, 10, 15, 30 and 60. Digital photography and spectral images were used to analyse haemoglobin and melanin content, and re-epithelialisation area. Pain was assessed by visual analogue scale. Scar characteristics were scored on days 30 and 60. Biomaterial samples were analysed for growth factor and protein content.
Results
The study included 24 patients (18 male and six female; mean age: 59.1 years). PRP was topically applied to wounds in 11 patients (13 donor sites) and ATE in 13 patients (15 sites). ATE-treated donor sites exhibited significantly accelerated wound re-epithelialisation on days 5 and 7 compared with control sites (p=0.003 and 0.04, respectively). PRP accelerated healing on day 7 compared with control sites (p=0.001). Additionally, the application of ATE improved scar quality on days 30 and 60 (p=0.0005 and 0.02, respectively). Pain scores did not differ significantly between treatments.
Conclusion
In this study, both growth factor sources stimulated wound healing. ATE is an alternative source of growth factors that promote early wound healing and improve scar quality.
The treatment and regeneration of maxillofacial bone defects are complex and pose significant challenges to surgeons and scientists. Several techniques are available in the clinical setting for surgeons to treat large bone defects of the jaws, including autogenous bone grafting (i.e. non-vascularized and vascularized bone grafts), reconstruction plates, titanium mesh combined with growth factors and biomaterials, and distraction osteogenesis. Three-dimensional (3D) printing and bone tissue engineering (BTE) strategies is an exciting minimally invasive alternative to bone harvesting techniques to replace missing bone of the mandible and the maxilla. Advances in the fields of computer-assisted planning, 3D printing technology, and BTE over the past few decades offer promising new treatment alternatives using biocompatible scaffold materials, autologous mesenchymal stem cells and growth factors. The use of these techniques might have the potential to profoundly improve patients’ function, form, and quality of life. These approaches have provided a new platform for basic and translational research and have shown promising results for maxillofacial regeneration. The purpose of this chapter is to provide a variety of different current evidence-based treatment options, as well as novel tissue engineering technologies for the reconstruction of large jaw defects.KeywordsMaxillofacial regeneration3D printingTissue engineeringScaffoldsBiomaterialsStem cellsGrowth factors
Patients who use full dental prostheses for long periods of time usually experience bone resorption in the alveolar process and in keratinized mucosa. This can cause instability, low prosthetic retention, and subsequent loss of function. Treating a patient with a severely atrophic mandible is quite challenging due to the low bone height and thickness, potentially impairing rehabilitation, aesthetics, and functional recovery. Several techniques are used to reconstruct major vertical defects for the installation of dental implants. Among these is the “tent pole” technique, which features low morbidity and generally produces good results in the form of increased height of the alveolar ridge bone. Herein we describes a patient with a severely atrophic mandible, reconstructed using a plate and dental implants. We employed a modified “tent pole” technique using an autogenous graft of the iliac crest and without use of platelet-rich plasma concentrate. Our results indicate that the modified tent pole technique using the iliac crest graft, and without use of platelet-rich plasma, is a safe and effective method for achieving mandibular reconstruction while restoring function, aesthetics, and the patients’ quality of life.
Microbeads consisting of pullulan and dextran supplemented with hydroxyapatite have recently been developed for bone tissue engineering applications. Here, we evaluate the bone formation in two different preclinical models after injection of microbeads reconstituted with either saline buffer or autologous blood. Addition of saline solution or autologous blood to dried microbeads packaged into syringes allowed an easy injection. In the first rat bone defect model performed in the femoral condyle, microcomputed tomography performed after 30 and 60 days revealed an important mineralization process occurring around and within the core of the microbeads in both conditions. Bone volume/total volume measurements revealed no significant differences between the saline solution and the autologous blood groups. Histologically, osteoid tissue was evidenced around and in contact of the microbeads in both conditions. Using the sinus lift model performed in sheep, cone beam computed tomography revealed an important mineralization inside the sinus cavity for both groups after 3 months of implantation. Representative Masson trichrome staining images showed that bone formation occurs at the periphery and inside the microbeads in both conditions. Quantitative evaluation of the new bone formation displayed no significant differences between groups. In conclusion, reconstitution of microbeads with autologous blood did not enhance the regenerative capacity of these microbeads compared to the saline buffer group. This study is of particular interest for clinical applications in oral and maxillofacial surgery.
The composite film prepared from a combination of biomaterials such as natural, ceramic, and synthetic polymers can support the growth of different types of tissues. Silk fibroin (SF) used in this study is extracted from ecorace of Tasar cocoon (Railey, Daba, and Baraf), which is locally available in our State (Chhattisgarh). The silk fibroin from these three different ecoraces was allowed to blend with hydroxyapatite (HAP) and chitosan (CS). According to the literature, SF and CS are nontoxic, non-immunogenic, biodegradable, and biocompatible. Whereas hydroxyapatite (HAP) possesses good biocompatibility with bone tissue and have the property of osteoconductivity. Hence, this tri-composite film unites both organic and inorganic components to promote osteoinduction and osteoconduction property in an ideal configuration. The structural characterization of the film was analyzed using Fourier transform infrared spectroscopy (FTIR), SEM techniques, and the hemocompatibility of the composite film was calculated to test the compatibility of the constructed film. It is expected that the resulting film when seeded with mesenchymal stem cells would become a highly functional bone tissue substitute and further optimization work will be done to achieve this goal.
Hair regenerative medicine is a promising approach for the treatment of hair loss and involves the transplantation of follicular stem cells into bald spots to regenerate hair. Various approaches have been investigated to engineer tissue grafts for use in hair regenerative medicine. Tissue-like three-dimensional aggregates, such as bioengineered hair follicle germs (HFGs), have shown great promise for hair regeneration, with normal tissue morphology and hair cycles. However, these approaches have not yet been applied in clinical settings, and further studies are needed to improve hair generation efficiency. The biological molecules in in vivo microenvironments around HFGs may provide cues for the in vitro preparation of HFGs with higher trichogenic functionalities. Activated platelet-rich plasma releasate (PRPr) is an autologous source of signaling molecules including growth factors and cytokines. In this study, we investigated the effects of PRPr on the preparation of HFGs in vitro. The presence of PRPr did not hinder the spontaneous formation of dumbbell-like HFGs from a suspension of embryonic skin-derived epithelial and mesenchymal cells in a custom-designed HFG culture plate. HFGs prepared with PRPr displayed greater levels of follicular gene expression compared to those prepared in the absence of PRPr. Moreover, the hair regeneration ability upon intracutaneous transplantation was significantly improved in the presence of PRPr. These results suggest that PRPr is beneficial for engineering HFGs for autologous hair regenerative medicine.
Reconstruction of bone defects represents a serious issue for orthopaedic and maxillofacial surgeons, especially in extensive bone loss. Adipose-derived mesenchymal stem cells (ADSCs) with tri-calcium phosphates (TCP) are widely used for bone regeneration facilitating the formation of bone extracellular matrix to promote reparative osteogenesis. The present study assessed the potential of cell-scaffold constructs for the regeneration of extensive mandibular bone defects in a minipig model. Sixteen skeletally mature miniature pigs were divided into two groups: Control group and scaffolds seeded with osteogenic differentiated pADSCs (n = 8/group). TCP-PLGA scaffolds with or without cells were integrated in the mandibular critical size defects and fixed by titanium osteosynthesis plates. After 12 weeks, ADSCs seeded scaffolds (n = 7) demonstrated significantly higher bone volume (34.8% ± 4.80%) than scaffolds implanted without cells (n = 6, 22.4% ± 9.85%) in the micro-CT (p < 0.05). Moreover, an increased amount of osteocalcin deposition was found in the test group in comparison to the control group (27.98 ± 2.81% vs 17.10 ± 3.57%, p < 0.001). In conclusion, ADSCs seeding on ceramic/polymer scaffolds improves bone regeneration in large mandibular defects. However, further improvement with regard to the osteogenic capacity is necessary to transfer this concept into clinical use.
Regeneration of large jaw bone defects still remains a clinical challenge. To avoid incomplete bone repair, bone grafts have been advocated to support the healing process. This study comparatively evaluated new bone formation among a synthetic graft substitute, a human bone derivative, and a bovine xenograft. Materials were placed in 3 out of the 4 bone cavities, while 1 deficit was left empty, serving as a control, in mono-cortical defects, surgically prepared in the porcine calvaria bone. Animals were randomized in 2 groups and euthanized at 8 and 12 weeks. Harvested tissue specimens were qualitatively evaluated by histology. New bone formation was quantitatively measured by histomorphometry. Maximum new bone formation was noticed in defects grafted with beta-tricalcium phosphate b-TCP compared to the other bone substitutes, at 8 and 12 weeks post-surgery. Bovine and human allograft induced less new bone formation compared to empty bone cavity. Histologic analysis revealed that b-TCP was absorbed and substituted significantly, while bovine and human allograft was maintained almost intact in close proximity with new bone. Based on our findings, higher new bone formation was detected in defects filled with b-TCP when compared to bovine and human graft substitutes.
Aim
This review critically appraises the available knowledge on the pre‐clinical and clinical use of bioactive factors for bone regeneration in the cranial and maxillo‐facial area.
Materials and Methods
The use of growth factors, amelogenins and autologous platelet concentrates (APCs) for bone regeneration was reviewed in a systematic manner. More specifically, preclinical and clinical studies on ridge preservation, alveolar ridge augmentation, regeneration of peri‐implant defects and sinus augmentation models were considered.
Results
Amongst different bioactive factors, the highest pre‐clinical and clinical evidence of a positive effect on bone formation is associated with BMP‐2 and the lowest with amelogenins. While APCs seem to accelerate clinical healing and reduce postoperative discomfort, there is insufficient and contrasting evidence of a significant effect on hard tissue regeneration for the different clinical applications.
Conclusions
Although there is increasing evidence that bioactive factors might enhance the bone regeneration process, the great heterogeneity of the available studies and the limited number of RCTs do not allow to draw robust conclusions. Issues that still need to be investigated include the optimal carriers for bioactive agents (direct vs. indirect), the dosage, the timing of administration, as well as the possibility of combining different agents to promote synergistic effects.
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Purpose:
The study aimed to investigate through histology, histometry, and immunohistochemistry the vital bone formation after grafting of biphasic calcium phosphate bioceramic (BC) in combination with calvarial autogenous bone into the dental sockets of rats.
Materials and methods:
Forty-five male rats were submitted to upper right incisor extraction and divided according to the grafted material in: control, bioceramic (BC), and bioceramic + autogenous bone (BC + AB). The animals were killed 7, 21, and 42 days after surgery for histological, histometric, and immunohistochemistry analysis.
Results:
Histomorphometric results demonstrated, for BC + AB group, formation of trabecular bone between the particles of BCs and autogenous bone, connecting them, as well as higher percentage of vital bone in comparison with BC. Immunohistochemical reactions showed intense labeling for Runx2-positive cells in the group BC + AB.
Conclusions:
Autogenous bone was able to stimulate bone turnover enabling a larger amount of vital bone synthesis and can be recommended as a viable grafting material in combination with synthetic biphasic BC.
Platelet-rich plasma (PRP) has been established as an autologous source for therapeutic angiogenesis. The purpose of this study was to evaluate PRP angiogenic effects compared to platelet-poor plasma (PPP) in vitro and in vivo. The effects of PRP on vascular endothelial growth factor receptor-2 (VEGFR2) and CD34 expression were evaluated using real-time PCR, flow cytometry, western blot, immunocytochemistry and pathological study, as were carried out in both human umbilical endothelial cell culture and rat skin. Our findings indicated significant effect of PRP and PPP on VEGFR2 and CD34 expression by human umbilical vein endothelial cells, which was greater in latter. These effects, however, were confirmed by demonstrating an earlier angiogenic effect of PPP in vivo when compared to PRP. The findings of the present study as the first comparative study of PRP versus PPP are novel. Nevertheless, further studies are needed to clarify the underlying mechanism of these findings to improve the therapeutic effects of PRP and PPP.
The relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation was examined in primary diploid cultures of fetal calvarial derived osteoblasts by the combined use of autoradiography, histochemistry, biochemistry, and mRNA assays of osteoblast cell growth and phenotypic genes. Modifications in gene expression define a developmental sequence that has 1) three principle periods–;proliferation, extracellular matrix maturation, and mineralization–;and 2) two restriction points to which the cells can progress but cannot pass without further signal–;the first when proliferation is down-regulated and gene expression associated with extracellular matrix maturation is induced, and the second when mineralization occurs. Initially, actively proliferating cells, expressing cell cycle-and cell growth-regulated genes, produce a fibronectin/type I collagen extracel-lular matrix. A reciprocal and functionally coupled relationship between the decline in proliferative activity and the subsequent induction of genes associated with matrix maturation and mineralization is supported by 1) a temporal sequence of events in which there is an enhanced expression of alkaline phos-phatase immediately following the proliferative period, and later, an increased expression of osteocalcin and osteopontin at the onset of mineralization; 2) increased expression of a specific subset of osteoblast phenotype markers, alkaline phosphatase and osteopontin, when proliferation is inhibited by hydroxyurea; and 3) enhanced levels of expression of the osteoblast markers as a function of ascorbic acid-induced collagen deposition, suggesting that the extracellular matrix contributes to both the shutdown of proliferation and the development of the osteoblast phenotype.
Recent and ongoing research efforts have been made to increase the efficacy of biomaterials as structural fillers during in vivo bony reconstructions. Although the selection of the possible material choices has grown, a biomaterial that can be physically molded to the defect/void space as well as offer biomimetic tissue regeneration has yet to be made available. With the potential success of demineralized freeze-dried bone allografts (DFDBA) combined with tendonous collagen as an effective filling material, further research should help to elucidate its use. The purpose of this study was to evaluate the regenerative healing response of five allograft mixtures via the morphology of filled, periodontal defects. Critical size mandibular and maxillary osseous defects were surgically created in six adult baboons. The filling response of four combinations of DFDBA and tendon collagen was compared with an all-collagen graft after 3 months of implantation. The overall results indicate that all combinations of DFDBA and collagen provided a better fill response than the all-collagen matrix (P < 0. 05). Statistically, however, all of the combinations were similar (P > 0.05) with a 60:40 collagen to DFDBA mass ratio resulting in the largest defect fill response.
Alveolar bone regeneration is frequently necessary prior to placement of implants. Efforts to improve wound healing have focused on factors that may enhance bone formation following guided bone regeneration (GBR) techniques alone or in combination with bone replacement graft materials. Recent reports suggest that platelet-rich plasma (PRP), presumably high in levels of peptide growth factors, may enhance the formation of new bone when used in combination with autogenous graft material.
In this report, the clinical and radiographic results are presented on 15 consecutively treated patients using autologous PRP in combination with freeze-dried bone allograft (FDBA) for sinus elevation and/or ridge augmentation. FDBA and PRP (0.5 g/2cc PRP) were mixed and placed as a composite graft material. A gel formed by mixing autologous thrombin-rich plasma with PRP (1:4 ratio) was used to cover the graft material. Core biopsies of grafted areas were obtained in several patients as part of implant site preparation and were evaluated histologically to determine site maturation.
Of 36 implant fixtures, 32 (89%) were considered clinically successful demonstrating complete bone coverage of the implant, no mobility, and a normal radiographic appearance at the time of re-entry and 12 months post-implant exposure. Four implants were removed due to mobility at the time of surgical exposure. Histologic evaluation of biopsy specimens revealed numerous areas of osteoid and bone formation around FDBA particles, with no evidence of inflammatory cell infiltrate.
These clinical and histological findings suggest that ridge augmentation and sinus grafting with FDBA in combination with PRP provide a viable therapeutic alternative for implant placements. Future studies are necessary to determine whether PRP enhances new bone formation or maturation with bone replacement allografts.
Platelet-rich plasma is an autologous source of platelet-derived growth factor and transforming growth factor beta that is obtained by sequestering and concentrating platelets by gradient density centrifugation. This technique produced a concentration of human platelets of 338% and identified platelet-derived growth factor and transforming growth factor beta within them. Monoclonal antibody assessment of cancellous cellular marrow grafts demonstrated cells that were capable of responding to the growth factors by bearing cell membrane receptors. The additional amounts of these growth factors obtained by adding platelet-rich plasma to grafts evidenced a radiographic maturation rate 1.62 to 2.16 times that of grafts without platelet-rich plasma. As assessed by histomorphometry, there was also a greater bone density in grafts in which platelet-rich plasma was added (74.0% ± 11%) than in grafts in which platelet-rich plasma was not added (55.1% ± 8%; p = 0.005).
Unloaded cylindrical grit-blasted titanium (Ti-6A-4V) implants (6×10 mm) coated with hydroxyapatite ceramic were inserted into the proximal part of the humerus of 20 skeletally mature Labrador dogs. The implants were initially surrounded by a 2 mm gap. In 10 dogs, HA-coated implants without growth factor were inserted in one humerus and implants with 0.3 ug rh.TGF-61 adsorbed onto the HA coating were inserted in the contralateral humerus. In another group of 10 dogs, a dose of 3.0 mg rhTGF-β1 was tested in a similar design. All dogs were killed at 6 weeks after treatment. Results were evaluated by histomorphometry and mechanical push-out testing. Bone ongrowth was increased by one third, using the 0.3 mg rhTQF-β1 stimulation. Bone volume in the gap and mechanical testing showed no statistically significant differences between control and rhTGF-β1 stimulated implants. RhTGF-β1 only moderately enhanced bone ongrowth to hydroxyapatite-coated implants.
Bone metabolism is influenced by systemic and local acting hormons. Bone morphogenetic proteins (BMPs) as representatives of the latter substances are known to have the ability for ectopic bone formation. Within this study, we investigated the influence of different growth factors on the proliferation- and differentiation rate of osteoblast-like cells. For that purpose, human osteoblast-like cells (HPOC) were incubated in the presence of either recombinant BMP-4 of the genome of xenopus laevis (rxBMP-4), recombinant human BMP 2 (rhBMP-2), transforming growth factor-β (TGF-β) or basic fibroblast growth factor (rh-bFGF) in two different concentrations each (10 ng/ml and 50 ng/ml). Cell proliferation was measured within a MTT [3-(4,5- Dimethylthiazol-2-yl)2,5-Diphenyltetrazolium Bromid] assay, the amount of cell differentiation by the activity of alcaline phosphatase. Rx-BMP-4 induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied at the same concentration, failed to have any influence on cell differentiation. However, rh-bFGF provoked an increase in cell proliferation when compared with unstimulated HPOC, while rhBMP-2 and rxBMP-4 showed no effect on proliferation. TGF-β influenced bone proliferation as well as differentiation significantly. The equipotent effect of recombinant human BMP-2 and recombinant BMP-4 obtained from Xenopus laevis with regard to differentiation and proliferation of human primary osteoblast- like cells originates either in the fact that target cells have receptors for BMP 2 as well as BMP 4, or that both BMP's link to the same receptor with almost the same affinity.
In seven Goettingen minipigs 3.5–4.7-ml cancellous bone defects were created in the area of the tibial head on both sides. The defects were filled with α-TCP or β-TCP (tricalciumphosphate). ITI implants (Straumann, Freiburg, Germany) of 3.2 × 12-mm length were inserted into the underlying ceramic substitutes. Two additional pigs were used as control. Within the periods of observation (4, 16, 20, 28, 46, 68, and 86 weeks) fluorescent dyes were applied. Nondecalcified thin-sliced sections were examined by means of light and fluorescence microscopy. In addition microangiography and microradiography were performed. Bony regeneration occurred basally and on the sides of the defect according the angiogenetic reossification pattern. Resorption was due to a hydrolytic and cellular degradation process. After 46 weeks histomorphological evaluation showed an incomplete osseointegration of the simultaneously implanted dental implants. The bone contact surface ratio was lower than 25%. After 86 weeks 95–97% of both α- and β-TCP were resorbed. Ceramic residuals stayed within the newly formed trabeculae thus resisting further degradation until remodeling occurred. Both α- and β-TCP show a comparable degradation process. At the 86-week postoperative point only small residuals of the ceramic can be found. These residuals stay within the newly formed trabeculae, which show a functional orientation. In comparison control defects showed only sparse reossification. The β-TCP material shows an accelerated degradation mode and has an optimal reactivity with the surrounding tissues. According to the results of this animal experiment both materials can be classified as bone-rebuilding materials. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 115–121, 2002; DOI 10.1002/jbm.10084
In a prospective study, 20 patients who underwent harvesting of chin grafts as outpatients, were followed up for 12 months (3 further patients with incomplete follow-up data were excluded from the study). Preoperatively and 7 days, 1, 3, 6 and 12 months postoperatively, follow-up data were assessed. Evaluation of the superficial sensory function of the inferior alveolar nerve was determined by the Pointed-Blunt Test and the Two-Point-Discrimination Test. Sensory disturbances were objectively assessed by testing thermal sensitivity with the “Pain and Thermal Sensitivity” Test (PATH Test). In addition, evaluation of the pulp sensitivity of teeth 35–45 was carried out by cold vitality testing. One week postoperatively, 8 patients were affected by superficial sensory impairment. 8 nerve territories showed hypoaesthetic reactions and 5 showed hyperaesthetic reactions. After 12 months, two patients still suffered from hypoaesthesia of one side of the chin. There was a statistically significant sensitivity impairment of the chin for all patients comparing the preoperative data of the Two-Point-Discrimination Test (left/right median: 8.17/8.17 mm, interquartile range (IQR) 1.00/2.00 mm) with the first postoperative measurement (left/right median 9.00/8.33 mm, IQR 1.67/2.66 mm). Comparing the latter to the last postoperative measurement there was significant tendency for regeneration of a nerve function (left/right median 8.00/7.84 mm, IQR 0.66/2.00 mm). In the PATH Test all hypoaesthetic areas could be identified by a reduction of thermal sensitivity. After the first postoperative examination 21.6% (n=38/176) of the examined teeth had lost their pulp sensitivity. After 12 postoperative months 11.4% (n=20/176) still did not react sensitively. Many of these were canines (n=8/20). Comparing the preoperative to the first postoperative examination, there was a significant reduction of pulp sensitivity. However, statistically significant recovery until the last postoperative follow-up could not be detected. The assessed data show that patients have to be informed extensively about disturbances of the inferior alveolar nerve function lasting longer than 12 months. Moreover, the loss of pulp sensitivity is a very frequent event which has always to be taken into account. Considering the high rate of complications with harvesting of chin grafts, more prospective trials should be done to find out whether there are other donor sites for autogenous bone which put less strain on patients.RésuméDans une étude prospective, 23 patients (d’un âge moyen de 45±17 ans, quatorze femmes et neuf hommes, et trois désistements) qui avaient subi la prise de greffon au niveau du menton ont été suivis pendant douze mois. Des données ont été enregistrées avant l’opération ainsi que sept jours, un, trois, six et douze mois après l’opération. L’évaluation de la fonction sensorielle superficielle du nerf alvéolaire inférieur a été déterminée par le test de la pression à l’aide d’une sonde dentaire et le test de discrimination de deux points. Les perturbations sensorielles ont été mesurées objectivement (en évaluant la sensibilité thermique) au moyen du test de la sensibilitéà la douleur et thermique (Test PATH). De plus l’évaluation de la sensibilité pulpaire des dents 35 à 45 a été mesurée par le test de vitalité au froid. Une semaine après l’opération huit patients souffraient d’un problème de sensibilité superficielle. Huit territoires nerveux montraient de l’hypoanésthésie et cinq des réactions d’hyperanésthésie. Après douze mois deux patients souffraient toujours d’hypoanésthésie d’un côté du menton. Il y avait une perte de sensibilité statistiquement significative du menton pour tous les patients en comparant les données préopératoires du test de discrimination de deux points (moyenne gauche/droite 8,17/8,17 mm, échelonnement [IQR] 1,00/2,00 mm) à la première mesure postopérative (moyenne gauche/droite 9,00/8,33 mm, IQR 1,67/2,66 mm). En comparant cette dernière à la dernière mesure postopérative il y avait une tendance significative à la régénération de la fonction nerveuse (moyenne gauche/droite 8,00/7,84 mm, IQR 0,66/2,00 mm). Dans le test PATH, toutes les hypoanésthésies pouvaient être identifiées par une réduction de la sensibilité thermique. Après le premier examen postopératif 21,6% (n=38/176) des dents examinées avaient perdu leur sensibilité pulpaire. Douze mois après l’opération 11,4% (n=20/176) ne réagissaient toujours pas à la sensibilité. Les canines étaint principalement les plus affectées (n=8/20). En comparant les examens préopératifs au premier examen postopératif, il en résultait une réduction significative de la sensibilité pulpaire. Cependant, un retour à la normale significatif jusqu’au dernier suivi postopératoire n’a pas pûêtre mis en évidence. Ces données montrent que les patients doivent être très bien informés à propos des problèmes de la fonction nerveuse alvéolaire inférieure qui peuvent durer plus de douze mois. De plus la perte de la sensibilité pulpaire est un évènement trés fréquent qui doit toujours être pris en considération. Considérant le très haut risque de complication lors du prélèvement des greffons osseux au niveau du menton davantage d’études prospectives devraient être effectuées pour découvrir s’il y a d’autres sites donneurs d’os autogène qui affecteraient nettement moins les patients.ZusammenfassungIn einer prospektiven Studie wurden dreiundzwanzig Patienten (durchschnittliches Alter 44.6±16.5 Jahre, 14 weibliche und 9 männliche Patienten, 3 Ausfälle), bei welchen in der Kinnregion Knochentransplantate entnommen wurden, über einen Zeitraum von 12 Monaten nachuntersucht. Messungen wurden präoperativ, nach 7 Tagen, nach 1, 3, 6 und 12 Monaten durchgeführt. Die Untersuchung der oberflächlichen sensorischen Funktion des N. alveolaris inferior erfolgte mittels eines Tests mit einem stumpfen punktförmigen Instrument und durch den Zwei-Punkte-Diskriminationstest. Sensorische Störungen wurden durch Testung der Wärmeempfindlichkeit mit dem “Schmerz- und Wärmeempfindlichkeitstest” (PATH-Test) objektiviert. Zusätzlich wurde noch die Pulpenempfindlichkeit der Zähne 35–45 durch einen Vitalitätstest mittels Kälte bestimmt. Eine Woche nach der Operation waren 8 Patienten von einer oberflächlichen sensorischen Störung betroffen. Acht Nervengebiete zeigten Hypoästhesien und 5 Hyperästhesien. Nach 12 Monaten litten immer noch zwei Patienten an Hypoästhesien auf einer Seite des Kinns. Es bestand bei allen Patienten eine statistisch signifikante Einschränkung der sensorischen Funktion in der Kinnregion zwischen den präoperativen (links/rechts Median: 8.17/8.17 mm interquartile Bandbreite (IQR) 1.00/2.00 mm) und postoperativen (links/rechts Median 9.00/8.33 mm, IQR 1.67/2.66 mm) Messungen mittels des Zwei-Punkte-Diskriminationstests. Wenn die Messungen nach der Operation mit den letzten postoperativen Messungen verglichen wurden, so zeigte sich eine signifikante Tendenz zur Regeneration der Nervenfunktion (links/rechts Median 8.00/7.84 mm, IQR 0.66/2.00 mm). Mit dem PATH Test konnten alle Areale mit Hypoästhesien durch eine Reduktion der Wärmeempfindlichkeit identifiziert werden. Nach der ersten postoperativen Untersuchung hatten 21.6% (n=38/176) der untersuchten Zähne die Sensibilität der Pulpa verloren. Zwölf Monate postoperativ reagierten immer noch 11.4% (n=20/176) der Zähne negativ auf den Kältetest. Meist waren die Eckzähne betroffen (n=8/20). Wenn die präoperativen Messungen mit der ersten postoperativen Untersuchung verglichen wurden, so bestand eine statistisch signifikante Reduktion der Sensibilität der Pulpen. Eine statistisch signifikante Erholung bis zur letzten postoperativen Nachuntersuchung konnte jedoch nicht ausgemacht werden. Die erhobenen Daten zeigen, dass die Patienten ausführlich über Beeinträchtigungen der Funktion des Unterkiefernerven während mehr als 12 Monaten informiert werden müssen. Zudem ist der Verlust der Sensibilität der Pulpen sehr häufig anzutreffen und muss daher immer in Betracht gezogen werden. Wenn die hohe Komplikationsrate bei der Gewinnung von Knochentransplantaten in der Kinnregion in Betracht gezogen wird, so kommt man zum Schluss, dass mehr prospektive Untersuchungen durchgeführt werden sollten, um herauszufinden, ob andere Entnahmestellen für autologen Knochen bestehen, welche den Patienten weniger Probleme bereiten.<ResumenSe siguieron veintitrés pacientes (media de edad 44.6±16.5 años), en un estudio prospectivo durante doce meses (14 pacientes hembras y 9 varones, 3 se salieron), que se sometieron a recogida de injertos del mentón. Se valoraron los datos de seguimiento, preoperativamente, a los 7 días, 1, 3, 6 y 12 meses postoperativamente. La evaluación de la función sensorial del nervio alveolar inferior se determinó por medio del test Pointed-Blunt y el test de discriminación de dos puntos. Las alteraciones sensoriales se valoraron objetivamente probando la sensibilidad térmica con el test “Sensibilidad Térmica y dolorosa” (test PATH). Además la evaluación de la sensibilidad pulpar de los dientes 35–45 se llevó a cabo por medio del test de vitalidad al frío. Una semana tras la operación 8 pacientes se vieron afectados de un deterioro sensorial superficial. Ocho territorios nerviosos mostraron reacción hipoestésica, 5 hiperestésica. Tras doce meses dos pacientes todavía sufrían hipoestésia en un lado del mentón. Hubo un deterioro estadísticamente significativo de la sensibilidad del mentón para todos los pacientes comparando los datos preoperatorios del test de discriminación de dos puntos (media izquierda/derecha: 8.17/8.17 mm, rango intercuartil (IQR) 1.00/2.00 mm) a las primeras mediciones preoperatorias (media izquierda/derecha 9.00/8.33 mm, IQR 1.67/2.66 mm). Comparando esto con la última medida postoperatoria existió una tendencia significativa hacia la regeneración de la functión nerviosa (media izquierda/derecha 8.00/7.84 mm, IQR 0.66/2.00 mm). En el test PATH se pudieron identificar todas las áreas hipoestésicas al existir una reducción de la sensibilidad térmica. Tras el primer examen postoperatorio el 21.6% (n=176) de los dientes examinados perdieron su sensibilidad pulpar. Tras 12 meses postoperatorios 11.4% (n=20/176) no habían reaccionado sensitivamente todavía. Se afectaron los caninos preferentemente (n=8/20). Comparando los exámenes preoperatorios a los primeros postoperatorios se produjo una reducción significativa de la sensibilidad pulpar. De todos modos la recuperación estadísticamente significativa no se pudo detectar ni en el último control postoperatorio. Los datos valorados muestran que los pacientes deben ser informados extensivamente acerca de las alteraciones de la función del nervio alveolar inferior que duraran más de doce meses. Más aún, la pérdida de función pulpar es un acontecimiento muy frecuente que debe ser siempre tenido en cuenta. Considerando el alto índice de complicaciones con la recogida de injertos del mentón se deben realizar más experimentos prospectivos para averiguar si existen otros lugares para donar hueso autógeno que supongan menos perjuicio para el paciente.
Zusammenfassung Zur Optimierung der Osteoneogenese wurde Pro Osteon 500, koralliner Hydroxylapatit, mit dem osteoinduktiven Proteinkomplex Colloss beschichtet und fr 28, 84, 168 und 365 Tage im distalen Kaninchenfemur implantiert. Unbeschichtetes Material wurde kontralateral zur intraindividuellen Kontrolle untersucht. Histologisch war die Knochenanlagerung an die Implantatgranula, auch nach Beschichtung mit Colloss, nicht beeintrchtigt. Osteoid und Chondroid fanden sich nur sprlich. Nach 84 Tagen war der ursprngliche Geflechtknochen weitgehend in lamellren Knochen umgewandelt. Die Knochenneubildung nahm bis zur Liegezeit von 84 Tagen zu und betrug dann bis zur Liegezeit von 365 Tagen zwischen 49,8% und 58,7%. Diese Zunahme war unabhngig von der geringeren Dichte der das Implantat umgebenden Spongiosa. Nach Beschichtung mit Colloss war die Osteoneogenese um maximal 15,1%, jedoch statistisch nicht signifikant, gesteigert. Die Implantatgranula unterlagen nicht der Resorption. Abstract In order to optimize osteoneogenesis, Pro Osteon 500 (coralline hydroxylapatite) was coated with the osteoinductive protein complex Colloss and implanted in distal rabbit femurs for 28, 84, 168, and 365 days. Uncoated material was placed contralaterally and examined for intraindividual control. No impairment of bone formation on the implant granules was noted upon histological examination, as well as after coating with Colloss. Both osteoid and chondroid were sparsely found. After 84 days the original woven bone had been largely transformed into lamellar bone. Formation of new bone increased up to 84 days and from then on ranged from 49.8% to 58.7% up to 365 days. This increase was independent of the lower density of the cancellous bone surrounding the graft. Coating with Colloss promoted osteoneogenesis to a maximum of 15.1%, which, however, was not statistically significant. The implant granules were not subject to resorption.
Bone metabolism is influenced by systemic and local acting hormons. Bone morphogenetic proteins (BMPs) as representatives of the latter substances are known to have the ability for ectopic bone formation. Within this study, we investigated the influence of different growth factors on the proliferation- and differentiation rate of osteoblast-like cells. For that purpose, human osteoblast-like cells (HPOC) were incubated in the presence of either recombinant BMP-4 of the genome of xenopus laevis (rxBMP-4), recombinant human BMP 2 (rhBMP-2), transforming growth factor-ß (TGF-ß) or basic fibroblast growth factor (rh-bFGF) in two different concentrations each (10 ng/ml and 50 ng/ml). Cell proliferation was measured within a MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromid] assay, the amount of cell differentiation by the activity of alcaline phosphatase. Rx-BMP-4 induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied at the same concentration, failed to have any influence on cell differentiation. However, rh-bFGF provoked an increase in cell proliferation when compared with unstimulated HPOC, while rhBMP-2 and rxBMP-4 showed no effect on proliferation. TGF-ß influenced bone proliferation as well as differenciation significantly. The equipotent effect of recombinant human BMP-2 and recombinant BMP-4 obtained from Xenopus laevis with regard to differentiation and proliferation of human primary osteoblast-like cells originates either in the fact that target cells have receptors for BMP 2 as well as BMP 4, or that both BMP's link to the same receptor with almost the same affinity.
Der osteoplastische Ersatz mehr oder weniger ausgedehnter Abschnitte der Gesichtsschädelknochen kann als Folge angeborener Dysostosen, Defektfrakturen, Tumorresektionen, Osteomyelitiden und altersbedingter Kieferatrophien indiziert sein. Er erfordert umfassende Kenntnisse der Knochenbiologie und ein sicheres Beherrschen der verschiedenen Operationstechniken, sowohl bezüglich der Gewinnung und Einlagerung der Knochentransplantate als auch der Aufbereitung der Transplantatlager. Der Wiederherstellung der einzelnen Knochenabschnitte kommt sowohl eine ästhetische als auch funktionelle Bedeutung zu. Dabei ist zu berücksichtigen, daß der gesamte Gesichtsschädel in lebenswichtige Funktionen wie Kau- und Schluckakt, Atmung und Sprache integriert ist [46].
Little consistency has been manifest among investigators in choosing an appropriate experimental model for maxillofacial bone research. In an effort to develop a protocol for the experimental analysis of maxillofacial nonunions, previous studies using calvarial and mandibular defects as models were reviewed. The creation of nonunions in animals within the calvaria and mandible was size dependent. Defects of a size that will not heal during the lifetime of the animal may be termed critical size defects (CSDs). A rationale was postulated for testing bone repair materials (BRMs) using CSDs in a hierarchy of animal models. This rationale suggests that testing should be initiated in the calvaria of the rat and rabbit, followed by testing in the mandibles of dogs and monkeys. While calvarial CSDs have been established in the rat, rabbit, and dog, further research is necessary to determine the CSD in the calvaria of the monkey, as well as the mandibles of dogs and monkeys.
Bone morphogenetic protein and bone-derived growth factors are biochemical tools for research on induced cell differentiation and local mechanisms controlling cell proliferation. Bone morphogenetic protein irreversibly induces differentiation of perivascular mesenchymal-type cells into osteoprogenitor cells. Bone-derived growth factors are secreted by and for osteoprogenitor cells and stimulate DNA synthesis. Bone generation and regeneration are attributable to the co-efficiency of bone morphogenetic protein and bone-derived growth factors.
Rat bone marrow stromal cells comprise a heterogeneous mixture of cell lineages including osteoblastic cells. When grown in the presence of ascorbic acid, beta-glycerophosphate and 10(-8) M dexamethasone, osteoprogenitor cells within the population divide and differentiate to form bone nodules (Maniatopoulos et al., 1988, Cell Tissue Res., 254:317-330; Aubin et al., 1990, J. Bone Miner. Res., 5:S81) providing a useful model to investigate temporal and spatial changes in expression of osteoblastic markers. Immunocytochemistry was combined with Northern blotting, enzymatic assay, and radioimmunoassay to analyze the expression of bone-related proteins during the growth and differentiation sequence. By mRNA levels, protein production and/or enzymatic activity, expression of osteocalcin, bone sialoprotein, and alkaline phosphatase increased concomitantly with the development of bone nodules, while osteopontin mRNA levels decreased and those of SPARC/osteonectin did not change significantly. In older cultures with mineralizing nodules, mRNA levels for alkaline phosphatase and bone sialoprotein, but not osteocalcin, declined. Immunolabeling revealed that cells in early cultures stained poorly for SPARC/osteonectin and strongly for thrombospondin. Later, SPARC/osteonectin staining increased in most cells, while thrombospondin staining could be seen in both matrix and in cells, but with marked intercellular variability in intensity. At all time points studied, osteoblasts within bone nodules stained homogeneously for thrombospondin and alkaline phosphatase, and with marked heterogeneity of intensity amongst cells for SPARC/osteonectin and osteocalcin. Labelling with RCC455.4, a monoclonal antibody raised against rat calvaria cells which intensely labels osteoblasts and osteocytes (Turksen et al., 1992, J. Histochem. Cytochem., 40:1339-1352), co-localized with osteocalcin. Alkaline phosphatase activity and the amount of osteocalcin determined by both radioimmunoassay and immunolabelling decreased in very late cultures, a time corresponding to appearance of fully mineralized nodules. These studies indicate that the bone marrow stromal cell system is a useful model to study the temporal and spatial expression of bone-related proteins during osteogenesis and formation, mineralization, and maturation of bone nodules. Further, immunolabelling at the individual cell and single bone nodule level allowed discrimination of marked variability of expression of osteoblast markers during the differentiation sequence.
Unloaded cylindrical grit-blasted titanium (Ti-6A-4V) implants (6 x 10 mm) coated with hydroxyapatite ceramic were inserted into the proximal part of the humerus of 20 skeletally mature Labrador dogs. The implants were initially surrounded by a 2 mm gap. In 10 dogs, HA-coated implants without growth factor were inserted in one humerus and implants with 0.3 microgram rhTGF-beta 1 adsorbed onto the HA coating were inserted in the contralateral humerus. In another group of 10 dogs, a dose of 3.0 micrograms rhTGF-beta 1 was tested in a similar design. All dogs were killed at 6 weeks after treatment. Results were evaluated by histomorphometry and mechanical push-out testing. Bone ongrowth was increased by one third, using the 0.3 mg rhTGF-beta 1 stimulation. Bone volume in the gap and mechanical testing showed no statistically significant differences between control and rhTGF-beta 1 stimulated implants. RhTGF-beta 1 only moderately enhanced bone ongrowth to hydroxyapatite-coated implants.
The aim of our study was a radiographic, endoscopic, and ultrasound follow-up of the maxillary sinus comparing 2 techniques of sinus floor augmentation.
Sonograms, radiographs (Waters' view) of the sinuses, and endoscopy served before and during surgery to evaluate the maxillary sinus. One week after the operation, ultrasound and radiograph follow-up (Waters' view) were carried out. Six months after the operation, we performed an ultrasound follow-up along with uncovering the implants. If any pathologic condition was found, we took another x-ray film of the sinuses, performed another endoscopic examination, or both.
In 23 of 63 patients, healing was uneventful. Waters' view revealed opacification of the maxillary sinus 1 week after surgery in 40 cases when the "window technique" was used. Sinusitis occurred 3 times, as a result of migration of bone chips in 2 patients. We lost 11 of 132 inserted implants during the healing and loading periods.
Endoscope-controlled sinus floor augmentation may lower the complication rate in a remaining height of the jaws between 4 and 8 mm. In our group of patients, we proved by endoscopic examination that migration of cancellous bone sequestra was the reason for sinusitis. In case of infected bone grafts with antral symptoms, sinoscopy allowed debridement and removal of a sequestrum.
Bone metabolism is influenced by systemic and local acting hormons. Bone morphogenetic proteins (BMPs) as representatives of the latter substances are known to have the ability for ectopic bone formation. Within this study, we investigated the influence of different growth factors on the proliferation- and differentiation rate of osteoblast-like cells. For that purpose, human osteoblast-like cells (HPOC) were incubated in the presence of either recombinant BMP-4 of the genome of xenopus laevis (rxBMP-4), recombinant human BMP 2 (rhBMP-2), transforming growth factor-beta (TGF-beta) or basic fibroblast growth factor (rh-bFGF) in two different concentrations each (10 ng/ml and 50 ng/ml). Cell proliferation was measured within a MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromid] assay, the amount of cell differentiation by the activity of alcaline phosphatase. Rx-BMP-4 induced a differentiation of HPOC to almost the same extent as rhBMP-2, whereas the addition of rh-bFGF, applied at the same concentration, failed to have any influence on cell differentiation. However, rh-bFGF provoked an increase in cell proliferation when compared with unstimulated HPOC, while rhBMP-2 and rxBMP-4 showed no effect on proliferation. TGF-beta influenced bone proliferation as well as differentiation significantly. The equipotent effect of recombinant human BMP-2 and recombinant BMP-4 obtained from Xenopus laevis with regard to differentiation and proliferation of human primary osteoblast-like cells originates either in the fact that target cells have receptors for BMP 2 as well as BMP 4, or that both BMP's link to the same receptor with almost the same affinity.
In order to optimize osteoneogenesis, Pro Osteon 500 (coralline hydroxylapatite) was coated with the osteoinductive protein complex Colloss and implanted in distal rabbit femurs for 28, 84, 168, and 365 days. Uncoated material was placed contralaterally and examined for intraindividual control. No impairment of bone formation on the implant granules was noted upon histological examination, as well as after coating with Colloss. Both osteoid and chondroid were sparsely found. After 84 days the original woven bone had been largely transformed into lamellar bone. Formation of new bone increased up to 84 days and from then on ranged from 49.8% to 58.7% up to 365 days. This increase was independent of the lower density of the cancellous bone surrounding the graft. Coating with Colloss promoted osteoneogenesis to a maximum of 15.1%, which, however, was not statistically significant. The implant granules were not subject to resorption.
Cranioplasty is the most common method for correcting cranial defects. A number of innovations have been made to optimize bone repair. Before their use in humans, extensive animal trials must be performed to establish efficacy. However, the literature provides only scant and inconsistent data regarding animal controls. The purpose of this study, therefore, was to determine the critical size cranial defect in the rabbit model. Cranial defects ranging from 0.5 to 1.5 cm were created in 18 New Zealand White rabbits. The rabbits were then killed at 9 and 18 weeks and the defects examined using CT imaging and histologic analysis to determine bone healing. It was determined that cranial defects greater than 1.5 cm failed to heal spontaneously. Thus, the critical size cranial defect in the rabbit model is 1.5 cm.
Combining platelet-rich plasma (PRP) with autogenous bone graft materials has recently been advocated as a means of enhancing rate and quality of new bone formation in regenerative procedures. The aim of this case series was to evaluate the potential of PRP in combination with bone allograft to enhance bone regeneration in alveolar ridge defects exhibiting both vertical and horizontal loss prior to the placement of dental implants. Augmentation resulted in clinical and radiographic gains in both vertical and horizontal components of the osseous defects, thereby facilitating subsequent placement of dental implants. Histologic evaluation of the cases revealed the presence of residual allograft particles surrounded by connective tissue as well as newly formed bone within the grafted areas. However, the addition of PRP did not appear to enhance the quality or quantity of new bone formation over that reported in comparable guided bone regeneration (GBR) studies without PRP.
Autologous platelet components were recently used as part of tissue-engineering strategies in oral and maxillofacial surgery. Various preparation methods were investigated to define standardized blood bank components and to collect data on the growth factor content of human platelets before and after storage.
Apheresis platelets (AP), buffy coat-derived platelets (BCP), platelets prepared by tube method (TP), and highly concentrated samples prepared from AP and from BCP were evaluated for standard quality criteria of platelet components and for their concentration of transforming growth factor (TGF)-ss1, platelet-derived growth factor (PDGF)-AB, and PDGF-BB. AP were stored for 5 days. On Days 3 and 5, these components and freshly prepared, highly concentrated samples were evaluated for the same measures.
Platelet concentration in TP was lower than that in the other groups (p<0.05). However, the concentrations of PDGF-AB, PDGF-BB, and TGF-ss1 were comparable in the three groups. TP showed higher spontaneous CD62 expression than did AP and BCP. The three preparation procedures resulted in significantly different WBC contamination, with the highest levels in TP. For the whole series of measurements, there was a strong correlation between growth factor levels and platelet concentration (p<0.05), which was due to the face that the growth factor content of concentrated platelet samples was tenfold that of AP, BCP, and TP. In TP, the WBC concentration was correlated with PDGF levels (p<0.05). After 5-day storage, the mean levels of PDGF-AB, PDGF-BB, and TGF-ss1 were 57.1, 43.0, and 72.0 percent of the initial values in AP. Overall, multiple regression analysis revealed the following factors influencing the measured growth factor concentrations: platelet concentration, baseline CD62 expression, lactate production, and WBC contamination.
Various methods enable the preparation of platelet components and of highly concentrated components for local use according to standard blood banking criteria. The obtained components differ, particularly in their WBC content and in vitro platelet activation. These findings are relevant for planning and evaluating further studies of locally usable autologous platelet components.
To evaluate changes in volume and structure of bone after autogenous iliac crest bone grafting to the maxilla. To discover the predictive value of computed tomographic (CT) measurements of bone density and study their correlation with the results of histomorphometric analyses of bone structure.
In 25 patients with atrophic maxillae (mean age 47 years, range 15-71), who had onlay bone grafting and sinus floor augmentation with autogenous iliac crest bone, a CT analysis was carried out immediately before and after grafting, and 5 months (range 4-6) later, at the time of endosseous implantation. On both occasions, bone biopsy specimens were taken. HISTOLOGY OF BONE: After preparing and digitizing semithin sections, histomorphometry (NH-Image) was done to establish the ratio of trabeculae to medullary cavity. CT ANALYSIS: The available transverse and vertical bone and the bone density of natural and augmented bone were analyzed using the Simplant Program and the CT data. As reference, the bone density of the first cervical vertebra was used. By regression analysis, the correlation of CT bone density and histological bone structure was investigated.
After a median healing period of 4.5 months, no significant changes were found in bone volume compared with the measurements made immediately after grafting. The changes in density in the cancellous portion of the grafted bone showed no correlation (correlation coefficient: +0.16) with the results of histomorphometric analysis of bone structure.
The predictive value of measurement of bone density to evaluate bone structure on the basis of the D1-D4 classification needs to be reconsidered. The most favourable time for secondary implantation is 4-6 months after iliac crest bone grafting.
Potential treatments using autologous thrombocyte growth factors are an important reason to improve methods for isolating platelet-rich plasma (PRP). Two methods for extracting PRP directly by the surgeon are currently available; this study was conducted to compare the growth factor levels in the resulting PRP.
Whole blood was drawn from 46 healthy donors (17 men, 29 women) aged 20 to 59 years (29.9 +/- 7.8). PRP was then separated from each sample by both the PCCS (3i) and Curasan (PRP Kit, Curasan) methods.
The growth factor content differed significantly for TGF-beta1 (PCCS 467.1 ng/mL; Curasan 79.7 ng/mL) (sign test P < .0001) and PDGF-AB (PCCS 251.8 ng/mL; Curasan 314.1 ng/mL) (P < .0001); this was less significant for IGF-I (PCCS 91.0 ng//mL; Curasan 69.5 ng/mL) (P < .02). The higher platelet count in the PCCS PRP (PCCS 2,232,500/microL; Curasan 1,140,500/microL) seemed to correlate with a higher level of TGF-beta1 (Spearman's correlation coefficient, r(s) = 0.7), whereas the higher leukocyte count in the Curasan PRP (PCCS 15,300/microL; Curasan 33,150/pL) had only a minor correlation with higher levels of PDGF-AB (r(s) = 0.46).
The PCCS end product has both a higher platelet count and a higher total content of the growth factors investigated. Nevertheless, the biologic effect of the evaluated growth factor levels remains unknown. The amount of PRP necessary to achieve the intended biologic effects still remains unclear.
PRP contains growth factors in high concentrations. Precise predictions of growth factor levels based on the thrombocyte counts of whole blood or PRP appeared limited. There are different sources for growth factors (platelets, leukocytes, plasma).
An important reason to improve methods of isolating platelet-rich plasma (PRP) is the potential use of autologous thrombocyte growth factors. In addition to discontinuous cell separation, two methods for extracting PRP that can be performed directly by the surgeon are now available. This study compared the suitability of these two methods for the preparation of PRP. Whole blood was drawn from 47 healthy donors (18 men, 29 women) aged 20-59 years (mean 29.9, SD 7.7). For each donor, PRP was separated by the PCCS method (PCCS Kit, 3i Implant Innovations, Palm Beach Gardens, FL, USA) and by the Curasan method (analogous to the PRP kit, Curasan, Kleinostheim, Germany). Thrombocyte counts differed significantly (sign test P = 0.001) between the donor blood (mean 290,000/ micro l, SD 86,000/ microl), the PCCS PRP preparation (mean 2,209,000/ microl, SD 901,000/ microl), and the Curasan PRP (mean 1,075,000/ micro l, SD 636,000/ microl). The correlation between the thrombocyte count in the PRP and the thrombocyte count in the donor whole blood was greater for the PCCS PRP (Spearman's correlation coefficient rS = 0.60) than for the Curasan PRP (r(S) = 0.34). A slight, clinically irrelevant, influence of gender on thrombocyte concentration in whole blood was found, but no influence of age was detected.
This paper reports on an experimental animal study evaluating a method of mandibular reconstruction. After a successful pilot study, 28 goats underwent a continuity resection of the mandibular angle. Primary reconstruction was carried out using specially designed osteosynthesis plates and screws. The defect was bridged by the original cortical scaffold, filled with an autogenous bone graft from the iliac crest. To accelerate bone healing, platelet-rich plasma (PRP) was mixed with the particulate bone graft in 14 goats. All goats had uneventful healing. The osteosynthesis plates and screws withstood immediate loading for periods varying from 3 weeks to 3 months. The use of PRP appeared to enhance bone healing considerably.
When dental implants are to be inserted, sinus floor augmentation is an effective treatment procedure to improve bone height in the posterior maxilla. In addition to autogenous bone material, allogenic materials, e.g. beta-tricalciumphosphate (beta-TCP), have been used successfully. The purpose of this study was to investigate whether the combination of beta-TCP with platelet-rich plasma (PRP) enhances bony regeneration and resorption of the tricalciumphosphate material. In a randomized prospective trial, 45 sinus floor elevations were performed in 39 patients. In 22 sites, PRP was added to the beta-TCP granules, while in 23 sites beta-TCP without PRP was used. Six months later, bone specimens were harvested from the augmented region during the implant insertion procedure. The formation of new bone was about 8-10% higher when PRP was applied. A faster degradation of the ceramic bone substitute was not observed. In conclusion, when PRP was added to beta-TCP, bone regeneration was supported to a small extent. However, the resorption of beta-TCP was not accelerated and foreign-body giant cells and soft tissue surrounding the beta-TCP granules were present.
Progressive development of the rat osteoblast phenotype in vitro
- Owen
Erfahrungen mit autogenen Beckenkammtransplantationen im Ober‐ und Unterkiefer ‐ Vergleich der anterioren und posterioren Entnahmetechnik
- Schenck C.
Mandibular reconstruction
- Fennis
Langzeitergebnisse mit dem Knochenersatzmaterial Bio‐Oss
- Schlegel K.A.
Resorbierbare Kunststoff‐Tamponaden zur Knochendefektfüllung im spongiösen Lager
- Merten H.A.
Curasan PRP kit versus PCCS PRP system
- Weibrich
Einwachsverhalten von Knochenersatzstoffen
- Günther