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Schema of the craniectomy and osteotomy. The trapezoid bone island (shaded area) was pushed backward (arrows).
Source publication
Calvarial defects sometimes require cranioplasty to protect the brain. Alloplastic materials, such as acrylic resin, hydroxyapatite ceramics, and titanium, involve various problems, such as vulnerability, infection, deformity resulting from growth, and high cost. We devised a new bone transport model in the rabbit based on the distraction osteogene...
Context in source publication
Context 1
... craniectomy (7 × 14 mm) and trapezoid bone (upper line 7 mm, lower line 10 mm, height 10 mm) osteotomy were performed in 12 and 10 rabbits, respectively, under the operating microscope using an electric drill with extreme caution to prevent damage to the dura mater. The schema of the procedure is shown in Fig. 2. Two rabbits underwent only craniectomy as ...
Citations
... Bioceramics are used for skull reconstruction; however, their osteointegration rate may vary according to their composition (37)(38)(39)(40)(41)(42)(43). Our experience with 14 cases proved that Si-HA, Si-Sr-HA, HA-Woll, and HA-Woll-Frit bioceramics produced a good cosmetic result with excellent biocompatibility and osteointegrity. ...
Purpose:
Bioceramics are currently in use to cover bone defects in orthopedics and craniofacial surgery. But their compatibility and efficacy in cranium were not investigated in detail. The aims of this study were to produce, characterize, and assess the biocompatibility and osteointegration of Si-HA, Si-Sr-HA, HA-Wollastonite, and HA-Wollastonite-Frit bioceramics.
Methods:
Bioceramics were implanted into the burr holes of 14 craniotomy patients who were followed up from three to 24 months. Radiologic and scintigraphic examinations were performed.
Results:
Osteoblastic activity quantified by scintigraphy increased from 6.865 to 22.991±1.682 from four to eight months in the HA-Woll group. Adding fritt into HA-Woll decreased osteoblastic activity at 10 months. Si-Sr-HA displayed significantly higher osteoblastic activity when compared to the craniotomy site at 12 months. The scintigraphic ratio of the bioceramic implanted regions to the craniotomy sites varied between 1.10 and 1.57. Osteoblast formation and establishment of the trabecular pattern of bone was observed in the surroundings of bioceramics in two patients.
Conclusion:
These bioceramics can be safely used to cover the burr holes of craniotomy patients, as well as to close the cranial bone defects.
... Cylindrical defects in the frontal or parietal bone of mouse, 132,211,212 rat, [213][214][215] and rabbit 134,216,217 have in many ways been the primary screening tools or point of entry for the assessment of many biomaterials. Like segmental defects, cylindrical defects have the value of being reproducible both in size and local anatomy. ...
This review provides an overview of animal models for the evaluation, comparison, and systematic optimization of tissue engineering and regenerative medicine strategies related to bone tissue. This review includes an overview of major factors that influence the rational design and selection of an animal model. A comparison is provided of the 10 mammalian species that are most commonly used in bone research, and existing guidelines and standards are discussed. This review also identifies gaps in the availability of animal models: (1) the need for assessment of the predictive value of preclinical models for relative clinical efficacy, (2) the need for models that more effectively mimic the wound healing environment and mass transport conditions in the most challenging clinical settings (e.g., bone repair involving large bone and soft tissue defects and sites of prior surgery), and (3) the need for models that allow more effective measurement and detection of cell trafficking events and ultimate cell fate during the processes of bone modeling, remodeling, and regeneration. The ongoing need for both continued innovation and refinement in animal model systems, and the need and value of more effective standardization are reinforced.
... Alloplastic materials such as acrylic resin, hydroxyapatite or titanium may be used for cranioplasty materials. However, some problems have been reported with the use of alloplastic materials, such as fragility, biocompatibility concerns regarding infection and high cost (Bouletreau et al., 2002;Hirano et al., 2006). ...
... xenogenic grafts are not used today because of potential problems associated with infectious disease transmission. Therefore, autologous bone grafting is today considered the best option to treat adult calvarial defects (Bouletreau et al., 2002;Hirano et al., 2006). Indeed, in severe cases such as our patient, split thickness calvarial or rib grafts often work quite well without the need for multiple operations. ...
Calvarial defects are common problems in craniofacial surgery. They may be explained by surgical interventions, infectious processes, cranial trauma or congenital anomalies. Calvarial defects are particularly challenging because they do not heal spontaneously in humans older than 24 months. The feasibility of using bifocal transport distraction osteogenesis to repair calvarial defects has been successfully evaluated in numerous experimental models. To our knowledge, it has not been used for the reconstruction of human skull defects. We report the first case of human calvarial defect healed by transport distraction osteogenesis.
... Pre-clinical investigations of new compounds to promote bone growth are often implemented in small animal models, such as the calvarial defect model. The calvarial defect has been extensively used in the past, in mouse (Lee et al 2001, Cowan et al 2004, Xiao et al 2003, rat (Bosch et al 1998, Cacciafesta et al 2001, Schliephake et al 2004, rabbit (Vikjaer et al 1997, Hirano et al 2006, Jan et al 2006 and dog (Sato and Urist 1985) models. In the rat, a full-depth calvarial bone defect is typically introduced on the midline with a trephine drill; a range of diameters has been reported, including 3 mm (Ozcelik et al 2004), 4 mm (Inoda et al 2004, Akita et al 2004, Mah et al 2004, 5 mm (Bosch et al 1998, Aybar Odstrcil et al 2005, Andreassen and Cacciafesta 2004, Donos et al 2004, 6 mm , 7 mm (Khouri et al 1996, Kanou et al 2005, 8 mm (Hong et al 2006, Blum et al 2003, Lutolf et al 2003, Sartoris et al 1987 and 9 mm (Arnaud 2000, Nussenbaum et al 2005. ...
The rodent calvarial defect model is commonly used to investigate bone regeneration and wound healing. This study presents a micro-computed tomography (micro-CT) methodology for measuring the bone mineral content (BMC) in a rat calvarial defect and validates it by estimating its precision error. Two defect models were implemented. A single 6 mm diameter defect was created in 20 rats, which were imaged in vivo for longitudinal experiments. Three 5 mm diameter defects were created in three additional rats, which were repeatedly imaged ex vivo to determine precision. Four control rats and four rats treated with bone morphogenetic protein were imaged at 3, 6, 9 and 12 weeks post-surgery. Scan parameters were 80 kVp, 0.45 mA and 180 mAs. Images were reconstructed with an isotropic resolution of 45 microm. At 6 weeks, the BMC in control animals (4.37 +/- 0.66 mg) was significantly lower (p < 0.05) than that in treated rats (11.29 +/- 1.01 mg). Linear regression between the BMC and bone fractional area, from 20 rats, showed a strong correlation (r(2) = 0.70, p < 0.0001), indicating that the BMC can be used, in place of previous destructive analysis techniques, to characterize bone growth. The high precision (2.5%) of the micro-CT methodology indicates its utility in detecting small BMC changes in animals.
Background:
Bone transport osteogenesis (BTO), distraction of a free portion of bone across a defect, offers an autologous solution to large cranial defects that may allow treatment without permanent hardware implantation. This study establishes a sheep model to evaluate the feasibility and distraction kinetics of BTO.
Methods:
Subtotal cranial defects (3.5 × 3.5 cm) were created in 10 young adult sheep and a transport segment (3.5 × 2 cm) traversed the defect at varying distraction rates (0, 0.5, 1.0, and 1.5 mm/day) using semi-buried cranial distractors. After a 6-week consolidation period, sheep were euthanized and the resultant bone was analyzed by CT, histology, and mechanical testing.
Results:
Gross examination, histology, and 3D CT revealed that control animals had fibrous nonunion whereas distraction animals had ossified defects with fibrous nonunion at the distal docking site. There was one premature consolidation in the 0.5 mm/day group. The volume of bony regenerate in the 0.5, 1.0, and 1.5 mm/day distraction rate groups was statistically indistinct (P = 0.16). The mean flexural moduli (MPa) of non-decalcified samples from the control cranium, transport segment, and bone regenerate were found to be 4.50 ± 4.9, 6.17 ± 2.1, and 4.14 ± 4.8, respectively (P = 0.24).
Conclusions:
This experiment provides proof of concept for BTO for large calvarial defects in a sheep model. Distraction at a rate of 0.5 mm per day may place individuals at higher risk for premature consolidation, but distraction rates did not have significant effects on regenerate quantity or quality. Future work will include the use of curvilinear distraction devices for 3-dimensional contour.
Transport distraction osteogenesis (TDO) has been used in attempts to treat large calvarial defects but has, until now, lacked consistency and reliability. To achieve sufficient bone formation, the effect of TDO was compared to the effect of TDO combined with recombinant human bone morphogenic protein-2 (rhBMP-2).
Fourteen dogs were divided into 2 groups; 6 animals in the control group received TDO only, and 8 received TDO combined with rhBMP-2. A calvarial defect 33 × 35 mm in size was generated, and the drug-delivering internal distractor was applied. After a 5-day latency period, distraction with rhBMP-2 at 10 μg/day was initiated at a rate of 2 mm/day. This was followed by a consolidation period of 3 months, after which areas of osteogenesis and strength were measured and histologic examinations were conducted.
The average area of osteogenesis was higher in the experimental group (P < 0.01). Regenerated bone of the experimental group showed increased strength (P < 0.05). Histological examination showed typical mature bone in the experimental group. Prominent osteoblastic rimming was observed in the bone marrow of the experimental group.
TDO with an internal distraction device delivering rhBMP-2 can enhance bone regeneration of large calvarial defects in a dog model. These results suggest the potential for human clinical testing of TDO combined with rhBMP-2.
According to previous reports about the experimental study of transport disk distraction osteogenesis (TDDO) for the reconstruction of bone defects, TDDO showed great feasibility of successful bone regeneration. However, those studies had some limitations in their design and analysis of the results, either. In this report, we intended to verify the effect of TDDO in the reconstruction of skull defects with a combined result of distraction osteogenesis and bone graft of transported disk (TD).
Six female dogs were operated on and were given a 35×15-mm bilateral skull defect. In the experimental group, TDDO with internal distractors (7×14-mm TD) was performed. On the other side, in the control group, the bone defects were left to heal naturally. The distraction was performed from the postoperative fifth day at a rate of 1 mm/d. The distraction progressed for 14 days, and then the TD was maintained in the middle of the bone defect area. The 40% of the original bone defect area was left the same as the control side. The TD was expected to be survived as a bone graft during the consolidation period. After 3½ months of a consolidation period, the remained bone defects were measured by three-dimensional computed tomography. The solidity of the new bone was compared with the bone tissue of the normal skull bone.
In the study group, the new bone formation was estimated to be 62.3% (SD, 25.1%) of the defect area, and in the control group, it was 44.8% (SD, 27.3%). The difference between the 2 groups was significant (P=0.04). The solidity of the newly generated bone by TDDO was not different from the normal skull (P=0.74).
In this study, the concept of TDDO and bone graft seemed to promote new bone formation. The role of the TD could include bone regeneration from distraction osteogenesis as well as autogenous bone graft, although it needs more investigation. The relationship between the duration of distraction and the positive role of the TD as an autogenous bone graft in TDDO for better clinical application may be investigated.
The objective of this study was to investigate the feasibility of distraction osteogenesis with a nitinol shape memory alloy spring controlled by infrared light.
In each of 20 New Zealand white rabbits, a critical-size defect (15 x 10 mm) was made in the body of the mandible, and a 10 x 8-mm segmental osteotomy was performed just anterior to the defect to create a transporting disk. A heat-controlled distractor and a temperature detector were then inserted (experimental group). Nothing was attached to the other side of the mandible (control group). After a 2-day latency period, the distractor was activated by the infrared at a rate of once per day for 9 days. The contralateral side was treated with the same infrared light. Gross, radiographic, and histologic analyses and dual energy x-ray absorptiometry were performed at regular intervals.
In the experimental group, the mandibular defect was reconstructed, whereas in the control group it was not. The histologic appearance of regenerated bone was similar to that observed with traditional distraction osteogenesis.
Distraction osteogenesis using a nitinol spring controlled by infrared light is possible.
Reconstruction of bone defects is possible through distraction osteogenesis using small bone transport discs. The aim of this study was to evaluate the usability of transport disc distraction osteogenesis (TDDO) in the reconstruction of skull defects in an animal experiment.
Eleven mongrel female dogs were used. Craniectomy (33 x 15 mm) was performed on both sides of the parietal bone symmetrically. On the experimental site, the 7 x 15-mm transport bone disc was used for TDDO. The control site was left in the defect state. An external distraction device was used. The latency period was 5 days, the rate of distraction was 1 mm/d, and distraction was done for 26 days. After a 6-month consolidation period, a computed tomographic scan was performed. The area of regenerated bone was measured from the computed tomographic scan. The hardness was checked on the regenerated bone and the normal bone. A histologic examination of the regenerated bone was done.
Eight cases were included in the evaluation, and 3 cases were excluded because they showed early escape of the distraction device. The mean (SD) area of the regenerated bone was 57.1% (26.3) in the experimental site and 41.8% (21.3) in the control site, which was not a statistically significant difference (P > 0.05). The mean (SD) hardness was 0.50 (0.17) MPa in the experiment site and 0.55 (0.29) MPa in the normal calvarial bone; the difference was not statistically significant (P > 0.05). On histologic examination, membranous ossification was found in the regenerated bone in the experimental site.
Transport disc distraction osteogenesis can induce new bone formation with hardness comparable to that of a normal bone. However, the amount of regenerated bone is not sufficient to allow TDDO to be substituted for conventional autogenous bone grafts.
