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(A) Higher magnification of Fig. 3A. A very limited amount of immature osteoid formation around the graft material was noted. (B) Higher magnification of the area marked in Fig 3B. Osteoid formation was noted around the graft material (▸). The newly generated bone seems well integrated with the graft material (⋆) (H&E staining).
Source publication
Fibronectin (FN) has been shown to stimulate bone regeneration in animal models. The aim of this study was to evaluate the capacity of bovine bone mineral coated with synthetic oligopeptides to enhance bone regeneration in rabbit calvarial defects.
Oligopeptides including fibrin-binding sequences of FN repeats were synthesized on the basis of prima...
Citations
... This may interfere with the evolution of the inflammatory process due to the availability of osteogenic cells, thus masking the interpretation of the results (Miranda et al., 2012). Larger and more standardized bone defects have been traditionally created outside of the oral cavity, such as in the tibia, femur, and calvaria of mice and rabbits (Lee et al., 2010;Puricelli et al., 2010;Wang et al., 2017;Taz et al., 2018). These sites, however, are free of factors such as bacteria, salivary flow, changes in pH and chewing forces, which prevent the direct extrapolation of results to clinical dentistry. ...
Aims:
This experimental study aimed to evaluate the effects of a three-dimensional matrix of chitosan-gelatin (CG) associated with 1% hyaluronic acid (HA) on gingival healing and repairing of intrabuccal bone defects in rats.
Materials and methods:
Standardized bone defects were created in the region of the upper 1st molars of rats. Study groups were created according to bone defects (n=6/group) treatment: Control group (CO); blood clot; HA group; CG group, and HA+CG group. After 7 and 21 days, the animals were sacrificed for histological and histomorphometric analysis. Bone formation was quantified as the percentage of newly synthesized collagen, visualized by Gomori's trichromic. Clinical/macroscopic evaluation was based on predetermined scores of gingival healing.
Results:
Treatment with HA improved gingival healing at day 7, but no statistical differences were found among groups at day 21. The morphometric analysis demonstrated better results after the treatment of bone defects with both HA and CG on day 21. The three-dimensional structure of CG prevented the invasion of epithelial tissue into the defect, preserving its original volume.
Conclusions:
Isolated use of a chitosan-gelatin osteoconductive matrix promoted greater bone deposition and preserved the volume of the surgical site, irrespective of the presence of hyaluronic acid.
... This may interfere with the evolution of the inflammatory process due to the availability of osteogenic cells, thus masking the interpretation of the results (Miranda et al., 2012). Larger and more standardized bone defects have been traditionally created outside of the oral cavity, such as in the tibia, femur, and calvaria of mice and rabbits (Lee et al., 2010;Puricelli et al., 2010;Wang et al., 2017;Taz et al., 2018). These sites, however, are free of factors such as bacteria, salivary flow, changes in pH and chewing forces, which prevent the direct extrapolation of results to clinical dentistry. ...
Abstract
Aim: This experimental study aimed to evaluate the effects of a three-dimensional matrix
of chitosan-gelatin (CG) associated with 1% hyaluronic acid (HA) on gingival healing
and repairing of intrabuccal bone defects in rats.
Methods: Standardized bone defects were created in the region of the upper 1st molars
of rats. Study groups were created according to bone defects (n=6/group) treatment:
Control group (CO); blood clot; HA group; CG group, and HA+CG group. After 7 and 21
days, the animals were sacrificed for histological and histomorphometric analysis. Bone
formation was quantified as the percentage of newly synthesized collagen, visualized
by Gomori’s trichromic. Clinical/macroscopic evaluation was based on predetermined
scores of gingival healing.
Results: Treatment with HA improved gingival healing at day 7, but no statistical differ�ences were found among groups at day 21. The morphometric analysis demonstrated
better results after the treatment of bone defects with both HA and CG at day 21. The
three-dimensional structure of CG prevented the invasion of epithelial tissue into the
defect, preserving its original volume.
Conclusion: Isolated use of a chitosan-gelatin osteoconductive matrix promoted greater
bone deposition and preserved the volume of the surgical site, irrespective of the pres�ence of hyaluronic acid.
... В хирургии и стоматологии существует ощутимая потребность в разработке новых средств, увеличивающих эффективность костной пластики, имплантации и пародонтологического лечения. Для изучения эффективности и безопасности различных остеопластических материалов, клеточных продуктов и новых технологий для костной пластики широко используют модель критического дефекта теменных костей крыс [1][2][3][4]. ...
Using chitosan as the basis for osteoplastic material, we were dealt with its low biocompatibility. The critical assessment of it is poorly presented in the literature and does not have systematic approaches to solving. The aim of the study was to determine the effect of factors affecting chitosan charge and its free amino groups number on the biocompatibility of hydrogels. Biocompatibility of chitosan compositions were studied in male Wistar rats (n=90). The subcutaneous implantation of chitosan discs and hydrogel caused abundant leukocyte infiltration. The addition of β-glycerophosphate followed by dialysis slightly reduced the inflammatory response. Treatment with a solution of alkali NaOH and NaHCO3 buffer, on the contrary, intensified the inflammatory response. It is confirmed the effect of charged amino groups of chitosan on leukocyte taxis A decrease in the deacetylation degree (DD) of chitosan to 39.0% led to a statistically significant decrease in leukocyte infiltration. Saturation of chitosan hydrogels with PLA granules reduced by 16% the level of leukocyte infiltration, which was supposedly associated with a decrease in the volume of the hydrogel and an increase in the area of its interaction with blood plasma proteins, which reduce the positive charge of chitosan. The most significant reduction in leukocyte infiltration was achieved with a combination of deacetylated to 39.0% chitosan hydrogel with the addition of 16% by weight highly porous PLA granules.
... In vivo analyses of bone repair are mostly evaluated after creation of bone defects in animal models [7,30]. Traditionally, these defects are created in extra-oral sites [31]. However, for better dental research, it would be interesting to use a bone defect model with similar characteristics to the maxillofacial bone complex repair. ...
The treatment of intrabuccal bone defects and the search for new agents to optimize regeneration procedures are extremely valuable. The present experimental study aimed to evaluate the effects of orally administered Strontium Ranelate (SrR), in the repair of intrabuccal bone defects in rats. Twenty Lewis rats, divided in 4 groups (2 control and 2 test groups) were used and evaluated at 14 and 42 days. Standardized bone defects in the distal alveolar region of the first superior molar were created in all animals. Test groups received a daily dose of SrR (625 mg/kg), and control groups received a placebo. Bone neoformation within the defects were evaluated through histological and morphometric analysis. At 14 days, histological analysis revealed similar healing patterns between groups. However, at 42 days, the test group presented healing patterns with better tissue organization, compatible with slightly advanced bone maturation. At 14 days, morphometric analysis revealed a higher rate of bone deposition in the test group when compared to the control group (P<0.05). At 42 days, no significant differences between groups were observed in relation to morphometric parameters. SrR seemed to accelerate the process of bone neoformation.
... Fibronectin (FN)-derived peptides could improve osteoblast adhesion, spreading and mineralization [49]. Lee et al. used model of rabbit calvarial defect to find new bone formation enhanced by a fibrin-binding synthetic oligopeptide derived from FN [50]. In addition, Martino et al. reported the regenerative effects of FN III9-10/ 12-14 on enhancing platelet-derived growth factor-BB (PDGF-BB) and BMP-2 in a critical-size bone defect model [51]. ...
It has been well recognized that the modification of biomaterials with appropriate bioactive peptides could further enhance their functions. Especially, it has been shown that peptide-modified bone repair materials could promote new bone formation more efficiently compared with conventional ones. The purpose of this article is to give a general review of recent studies on bioactive peptide-modified materials for bone tissue repair. Firstly, the main peptides for inducing bone regeneration and commonly used methods to prepare peptide-modified bone repair materials are introduced. Then, current in vitro and in vivo research progress of peptide-modified composites used as potential bone repair materials are reviewed and discussed. Generally speaking, the recent related studies have fully suggested that the modification of bone repair materials with osteogenic-related peptides provide promising strategies for the development of bioactive materials and substrates for enhanced bone regeneration and the therapy of bone tissue diseases. Furthermore, we have proposed some research trends in the conclusion and perspectives part.
... 28 Based on this information, we tested various types of short peptides in our previous studies and identified F20 as being the most effective in inducing osteoblast differentiation. 7,[11][12][13]29 Whereas our previous studies focused on the effect of F20 in osteoblast differentiation, in the present study we investigated the molecular mechanism underlying these effects of F20. ...
Background:
In our previous studies, we demonstrated that a fibronectin (FN)-derived oligopeptide termed F20 stimulates osteoblast differentiation in vitro and bone formation in vivo. However, the fundamental molecular mechanism by which F20 stimulates osteogenesis remains unknown. Therefore, in this study we investigated the molecular mechanism underlying the effect of F20 in osteoblast differentiation.
Methods:
The role of F20 in osteoblast differentiation was examined using the mouse bone-marrow-derived ST2 cell line. The effect of Smad1/5 was determined following siRNA knockdown. Runx2, Alp, and Oc mRNA levels were determined by quantitative real-time PCR and their transcriptional activation was assessed using luciferase reporter assays. Erk phosphorylation was visualized via immunoblotting.
Results:
The synthetic oligopeptide F20 stimulated the expression of the bone marker genes Runx2, Alp, and Oc in ST2 cells via Smad and extracellular signal-regulated kinase (Erk)/ mitogen-activated protein kinases (MAPK) signaling pathways as did bone morphogenic protein 2 (BMP2). Furthermore, Runx2 acted as a transcription factor during F20-induced osteoblast differentiation.
Conclusion:
Collectively, these results indicate that F20 induces osteoblast differentiation with a pattern similar to that mediated by the BMP2 signaling pathway. As our previous data also showed that the FN-derived oligopeptide improved wound healing, we suggest that F20 might serve as a therapeutic biomolecule to facilitate periodontal tissue regeneration.
... Fibronectin (FN)-derived peptides have also shown to facilitate osteoblast adhesion, spreading and mineralization [185]. A fibrin-binding synthetic oligopeptide derived from FN was found to enhance new bone formation in rabbit calvarial defect model [187]. In addition, the multifunctional FN III9-10/12-14 greatly enhanced the regenerative effects of BMP-2 and PDGF-BB in a rat critical-size bone defect model [186]. ...
Background
Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration.
Methods
A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study.
Results
Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited.
Conclusion
Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge.
... As usage of the full-length FN protein might cause adverse effects such as inflammation and instability because of endogenous enzymatic degradation, a partial FN peptide was introduced that shows comparable levels of cell adhesion, proliferation, and differentiation as the full-length protein [20]. Based on this peptide, we had previously developed various types of recombinant FN peptides, which contain variable lengths of spanning amino acids between the PHSRN and RGD sequences, and reported their ability to enhance cell adhesion, proliferation, and differentiation [18,[21][22][23]. Among the peptides, we focused on a partial FN peptide which is composed of 20 amino acids between PHSRN and RGD named F20, with the sequence:PHSRNSITGTNLTPGYTITV YAVTGRGD, and used this peptide for dental implant surface modification for improving osseointegration using the previously described "biomimetic approach" [24]. ...
Our previous studies demonstrated that a recombinant fibronectin (FN)-derived oligopeptide that we named F20 stimulated osteoblast adhesion, proliferation, and differentiation in vitro and in vivo. In the present study, we used a synthetic oligopeptide and investigated the osteogenic potential of F20 coating on titanium discs, to stimulate superior osseointegration for dental implant surface modification. Surface characteristic analysis of titanium was performed by confocal laser scanning microscopy (CLSM) observation. Synthetic F20 was coated onto the machined or SLA titanium discs by an adsorption procedure. ST2 cells were seeded on the titanium discs. We evaluated cell adhesion with SEM and CLSM observation, cell proliferation with picogreen assay, and osteoblast differentiation with real-time PCR, ALP activity assay, immunoblot assay and ALP staining. FITC-labeled F20 coating on the discs was detected by fluorescence, showing good F20 adsorption and different coating patterns according to the surface roughness. In the SEM and CLSM observations, cells were well attached on the machined surface and greater stress fiber formation was seen on discs coated with F20 than on other discs. F20 stimulated cellular proliferation, as well as osteoblast differentiation through the extracellular signal-regulated kinase (Erk) signaling pathway. These cellular responses to F20 were slightly better on the machined titanium surface than the SLA surface. These results suggest that F20 promotes osteogenesis through the Erk pathway and is a suitable biomolecule for surface modification of dental implants for improved osseointegration.
... В хирургии и стоматологии существует ощутимая потребность в разработке новых средств, увеличивающих эффективность костной пластики, имплантации и пародонтологического лечения. Для изучения эффективности и безопасности различных остеопластических материалов, клеточных продуктов и новых технологий для костной пластики широко используют модель критического дефекта теменных костей крыс [1][2][3][4]. ...
We modified the techniques of 3D-morphometry using histological sections based on computer-generated 3D reconstruction and mathematical modeling. We compared the results of measurements obtained with the use of above methods and those taken with traditional methods based on the analysis of X-ray pictures. It was shown that the methods of 3D-morphometry we developed provided more precise evaluation of the size of newly formed bone tissue. Basis for technical recommendations to perform the 3D-morphometry at every stage, from surgery to morphological analysis, were proposed.
... Models for oral and maxillo-facial osseous healing have been developed in small animals (rat, rabbit) and in more evolved animals like swine, dog, sheep, and primates [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Smaller animals have well-de ned genetic backgrounds, are easy to handle and maintain, and are economically suited to most research settings for veri cation of basic biologic principles [24]. ...
ABSTRACT Bone and tooth loss, as a result of trauma, anatomical or congenital reasons, cancer, and periodontal disease, is a common therapeutic problem in the fields of cranio-maxillo-facial surgery and periodontics. The proposed techniques for the treatment of various bone defects encountered include bone grafts, bone substitutes, guided tissue regeneration, and distraction osteogenesis as well as their combinations. In addition, dental implants have been successfully utilized for the restoration of full or partial edentulism. The introduction and development of new therapeutic approaches and devices demand the use of appropriate animal models that present bone anatomy and healing comparable to human. Among other animal models, the pig is extensively documented in several biomedical areas and has been largely used in maxillo-facial surgery and implants dentistry-related research. Anatomical and physiological similarities with human in size, physiology, and bone biology contribute to a successful involvement of this animal to understand and treat various osseous lesions. However, improvements and standardization are requested with respect to consistency and discrimination abilities. The aim of this review is to provide a critical appraisal of the literature related to swine models for the evaluation of cranio-maxillo-facial osseous defect healing, regeneration, and bone-implant interface. This review should assist researchers in the field to select the most appropriate model for each dedicated purpose and also contribute to stimulate an innovative thinking on the use of porcine models.
