Pattern Of Bone Formation Research Articles

Bone remodeling effect of a chitosan and calcium phosphate-based composite.

Chitosan is a biocompatible polymer that has been widely studied for tissue engineering purposes. The aim of this research was to assess bone regenerative properties of an injectable chitosan and calcium phosphate-based composite and identify optimal degree of deacetylation (%DDA) of the chitosan polymer. Drill holes were generated on the left side of a mandible in Sprague-Dawley rats, and the hole was either left empty or filled with the implant. The animals were sacrificed at several time points after surgery (7–22 days) and bone was investigated using micro-CT and histology. No significant new bone formation was observed in the implants themselves at any time points. However, substantial new bone formation was observed in the rat mandible further away from the drill hole. Morphological changes indicating bone formation were found in specimens explanted on Day 7 in animals that received implant. Similar bone formation pattern was seen in control animals with an empty drill hole at later time points but not to the same extent. A second experiment was performed to examine if the %DDA of the chitosan polymer influenced the bone remodeling response. The results suggest that chitosan polymers with %DDA between 50 and 70% enhance the natural bone remodeling mechanism.

Influence of experimental alcoholism on the repair process of bone defects filled with beta-tricalcium phosphate

This study evaluated the effect of ethanol on the repair in calvaria treated with beta-tricalcium phosphate (β-TCP). Forty rats were distributed into 2 groups: Water group (CG, n = 20) and Alcohol Group (AG, n = 20), which received 25% ethanol ad libitum after an adaptation period of 3 weeks. After 90 days of liquid diet, the rats were submitted to a 5.0 mm bilateral craniotomy in the parietal bones; the left parietal was filled with β-TCP (CG-TCP and AG-TCP) and the contralateral only with blood clot (CG-Clot and AG-Clot). The animals were killed after 10, 20, 40 and 60 days. The groups CG-Clot and AG-Clot showed similar pattern of bone formation with a gradual and significant increase in the amount of bone in CG-Clot (22.17 ± 3.18 and 34.81 ± 5.49) in relation to AG-Clot (9.35 ± 5.98 and 21.65 ± 6.70) in periods of 20–40 days, respectively. However, in the other periods there was no statistically significant difference. Alcohol ingestion had a negative influence on bone formation, even with the use of β-TCP, exhibiting slow resorption and replacement by fibrous tissue, with 16% of bone formation within 60 days in AG-TCP, exhibiting immature bone tissue with predominance of disorganized collagen fibers. Defects in CG-TCP showed bone tissue with predominance of lamellar arrangement filling 39% of the original defect. It can be concluded that chronic ethanol consumption impairs the ability to repair bone defects, even with the use of a β-TCP biomaterial.

The Influence of Type 2 Diabetes Mellitus on the Osseointegration of Titanium Implants With Different Surface Modifications-A Histomorphometric Study in High-Fat Diet/Low-Dose Streptozotocin-Treated Rats.

Type 2 diabetes mellitus (T2DM) is a systemic disease that also compromises the bone healing capacity. In healthy individuals, surface modifications of dental implants are proven to increase bone response and implant success. The aim of this study was to clarify if the surface modifications also improve osseointegration in a setting with diabetes mellitus. T2DM was induced in 7 rats by a high-fat diet/low-dose streptozotocin injection. All animals received a hydroxyapatite (HA) implant, a sandblasted and acid-etched (SLA) implant, and a standard machined titanium implant for control in the tibia. After 4 weeks, thin-ground sections were produced, and the volume of new bone formation (nBV/TV) and bone-to-implant contact (nB.I/Im.I) were histomorphometrically analyzed. Both surface modifications led to an increase of osseointegration compared with the machined surface implant in rats with T2DM. nBV/TV was highest in the SLA implants, whereas nB.I/Im.I was highest in the HA group. Regardless of the surface modification, a superordinate regional pattern of new bone formation over the length of the implant was observed. Implants with HA coating and SLA surface modifications seem to have the potential to increase osseointegration also in T2DM rats when compared with a conventional machined surface.

Characterizing and Modeling Bone Formation during Mouse Calvarial Development.

The newborn mammalian cranial vault consists of five flat bones that are joined together along their edges by soft fibrous tissues called sutures. Early fusion of these sutures leads to a medical condition known as craniosynostosis. The mechanobiology of normal and craniosynostotic skull growth is not well understood. In a series of previous studies, we characterized and modeled radial expansion of normal and craniosynostotic (Crouzon) mice. Here, we describe a new modeling algorithm to simulate bone formation at the sutures in normal and craniosynostotic mice. Our results demonstrate that our modeling approach is capable of predicting the observed ex vivo pattern of bone formation at the sutures in the aforementioned mice. The same approach can be used to model different calvarial reconstruction in children with craniosynostosis to assist in the management of this complex condition.

Dynamics of alveolar bone healing after the removal of orthodontic temporary anchorage devices.

The aim of this study was to investigate the dynamics of alveolar bone formation and healing pattern after the removal of orthodontic temporary anchorage devices (TADs). Miniscrews (N=32) were inserted into the buccal inter-radicular alveolar bone in beagle dogs. Afterward, miniscrews were removed at different time points during a 13-week period and six different in vivo fluorescent markers were injected at 1, 2, 6, 8, 10, and 12weeks. Serial changes in bone apposition at the removal and intact control sites were evaluated using μCT, histology, and bone histomorphometry. Gradual bone apposition at the TAD removal site was noted with bone volume/tissue volume (BV/TV) reaching the level of the control alveolar bone by 7weeks. Histologically, newly formed woven bone was detected within the removal site which was distinct from the surrounding pre-existing alveolar bone at 13weeks. Accelerated mineral apposition rate (MAR) and bone formation rate (BFR) were noted between 2 and 6weeks in the removal site (P<0.05). Although MAR and BFR gradually decreased after its peak at 2-4weeks, BFR in the removal site was still higher than the control site at 10-12weeks (P<0.05). Spontaneous bone healing was noted after TAD removal with regional acceleration of MAR and BFR within 2-6weeks. However, the removal site was mainly filled with woven bone even after 13weeks, suggesting a longer healing period is required for the quality of the alveolar bone to reach levels comparable to the surrounding alveolar bone.

Bone repair induced by different bone graft substitutes in critical-sized defects in rat calvaria

Abstract Introduction The use of bone substitutes in grafting procedures as an alternative of the use of autogenous bone graft has been indicated, however, the direct comparison between these biomaterials has been little explored. Objective To evaluate the effect of different osteoconductive bone substitutes on the bone repair in critical-sized defects (CSDs) in rat calvaria. Material and method One CSD with an 8 mm diameter was made in each of the 40 rats used in this study. The animals were randomly allocated into 5 groups (n=8), according to the type of bone substitute used to fill the CSD: COA (Coagulum); AUT (autogenous bone); DBB (deproteinized bovine bone graft); HA/TCP (biphasic ceramic composed of hydroxyapatite and β-phosphate tricalcium); and TCP (β-phosphate tricalcium). A microtomographic analysis was performed to evaluate the remaining defect linear length (DLL) of the CSD and the volume of the mineralized tissues (MT) within the CSD at 3, 7, 15 and 30 days after the surgical procedure. In addition, a histometric analysis was performed to evaluate the composition of the repaired bone tissue (% Bone and % Biomaterial) at the 30-day period. Result It was shown that the COA had the lowest DLL and MT within the CSD. In addition, the COA presented the highest % of bone in CSD. The DBB had a higher MT and a higher % of bone substitute particles in the CSD than the AUT and TCP groups. The DBB and AUT groups presented higher % of bone in the CSD than the TCP group. Conclusion The use of the DBB promoted a better pattern of bone volume gain and formation compared to TCP and HA / TCP but was biologically inferior to the AUT.

The Clinical Application of Recombinant Human Bone Morphogenetic Protein 7 for Reconstruction of Alveolar Cleft: 10 Years' Follow-Up

The purpose of this study was to report on a 10-year assessment after the application of recombinant human bone morphogenetic protein 7 (rhBMP-7) for the reconstruction of alveolar clefts. This study was conducted as a prospective phase II clinical trial on 9 unilateral and 2 bilateral alveolar clefts that received rhBMP-7 (Osigraft; Stryker Biotech, UK). The mean age of thepatients at surgery was 10.4years. At 6months postoperatively, occlusal radiographs were taken to evaluate bone formation at the cleft site. Patients were followed within the routine cleft care pathway for 10years to monitor the impact of bone morphogenetic protein 7 on orthodontic treatments and maxillary growth. Radiographs were taken according to the standard cleft care protocol. The radiographic assessment of the unilateral cleft lip and palate cases suggested good bone formation with a Kindelan score of grade 1 or 2. The bilateral alveolar cleft cases had a score of grade 3 or 4, indicating failure or partial failure. The children with successful grafts underwent a routine orthodontic follow-up without incident. The maxillary growth appeared to be similar to that in cases grafted with autogenous bone. No long-term complications and no abnormal pattern of bone formation were detected. The study provides unique evidence on the long-term safety of rhBMP-7 when applied at the area of skeletal immaturity for the reconstruction of alveolar clefts in children.

Cortical bone adaptation and mineral mobilization in the subterranean mammal Bathyergus suillus (Rodentia: Bathyergidae): effects of age and sex.

The patterns of bone modeling and mineral mobilization (skeletal homeostasis) among mammals other than humans and laboratory rodents are still poorly known. In this study we assessed the pattern of bone formation and bone resorption in the femur of a wild population of Cape dune molerats, Bathyergus suillus (n = 41) (Bathyergidae), a solitary subterranean mammal with a marked extended longevity among rodents, and which also lives in a naturally deficient state of vitamin D. In order to determine ontogenetic and sex effects on histomorphometric parameters of transversal undecalcified bone sections, two-way ANOVA, linear mixed-effects model and regression statistical analyses were performed. During ontogeny, B. suillus increased their cross sectional area, cortical area and cortical thickness, and most importantly, they showed scarce endosteal bone resorption which resulted in a retained medullary cavity size during ontogeny. This resulted in a positively imbalanced bone modeling, where bone formation considerably surpasses bone loss by almost 100-fold in adulthood. This differs markedly from other terrestrial mammals with relatively thin cortical walls. Regarding bone loss and remodeling, three main processes involving intracortical resorption were observed: modeling-related bone loss in early postnatal growth; secondary osteon formation occurring in both sexes; and subendosteal secondary reconstruction observed only in females. The latter is accompanied by females having six-fold more relative bone loss than males, which is evidenced by the development of enlarged resorption cavities (RCs) distributed circumferentially around the medullary cavity. Males have smaller, more circular and randomly distributed RCs. In general, our data indicate no age-related decline in mineral content in B. suillus, and provides strong support for a pattern of sexual dimorphism in skeletal homeostasis, similar to that occurring in humans and other mammals, with females losing more bone throughout aging as compared to males due to reproductive factors. Interestingly as well, despite the high mechanical loads experienced during burrow construction, bone remodeling in B. suillus is kept at very low levels throughout their lifespan, and dense Haversian tissue never forms. This study represents the first comprehensive assessment of skeletal homeostasis in a subterranean mammal, and it enables a better understanding of the complex processes governing the acquisition and maintenance of bone properties in this species with extraordinary fossorial adaptations.

Imaging features of Ewing's sarcoma: Special reference to uncommon features and rare sites of presentation.

Ewing's sarcoma (EWS) commonly involves long bones with a permeative pattern of bone destruction and aggressive interrupted periosteal new bone formation. However, radiological features show wide variation and some presentations are uncommon, leading to diagnostic confusion. This study is aimed at studying the imaging features of proven EWS and highlight the uncommon features and rare sites of presentation. The imaging findings of 100 consecutive histopathologically proven EWS were analyzed retrospectively. All uncommon presentations with respect to age and site and morphology of lesion were observed. Most of the patients were below 20 years of age and 8% were younger than 5 years. Other than long bones, ribs, and pelvis, other sites considered to be rare and were noted in 25%. Extraosseous site involvement was 11%. Uncommon features included epiphyseal involvement (4%), sclerosis (4%), expansion of bone (8%), sunray spiculation (10%), calcification in soft tissue (8%), saucerization (4%), pathological fracture (5%), fluid-fluid level (2%), vertebra plana (2%), and lesion crossing the joint (13%). The uncommon observations included incidence in children <5 years (8%) and occurrence in craniofacial bones, spine, scapula, and clavicles and in extraosseous sites such as retroperitoneum, adrenals, or extremity. Uncommon findings included epiphyseal involvement, sclerosis, saucerization, calcification in soft tissue component, and pathological fracture and lesion crossing the joint.

Use of Bone Allograft With or Without Bone Marrow Aspirate Concentrate in Appositional Reconstructions: A Tomographic and Histomorphometric Study.

To evaluate bone allograft associated to bone marrow aspirate concentrate (BMAC), in maxillary reconstructions. Ten patients with alveolar bone deficiency in the anterior maxilla were randomly divided into control group (CG) and test group (TG). A bone block allograft was placed in both groups, but the graft was impregnated with BMAC only in TG. Computed tomography was performed 7 days (T1) and 6 months (T2) after the grafting procedure, and volume and bone density measurements were carried out. Histomorphometric analysis was performed at T2. Bone volume loss from T1 to T2 was significant only in TG. The bone density in the buccal region of the graft was significantly higher in TG than in CG. There was no significant difference between the groups, in respect to mineralized tissue (MT) and nonmineralized tissue (NMT), in that MT values were 37.77% ± 15.19% and 43.85% ± 10.94%, and NMT values were 62.15% ± 14.90% and 56.30% ± 10.72%, respectively, for CG and TG. The intragroup difference for the MT/NMT ratio was statistically significant in CG but not significant in TG. The use of BMAC resulted in an improved pattern of bone formation, with higher bone density in the peripheral regions of the graft.

Osteoinduction by Foamed and 3D-Printed Calcium Phosphate Scaffolds: Effect of Nanostructure and Pore Architecture.

Some biomaterials are osteoinductive, that is, they are able to trigger the osteogenic process by inducing the differentiation of mesenchymal stem cells to the osteogenic lineage. Although the underlying mechanism is still unclear, microporosity and specific surface area (SSA) have been identified as critical factors in material-associated osteoinduction. However, only sintered ceramics, which have a limited range of porosities and SSA, have been analyzed so far. In this work, we were able to extend these ranges to the nanoscale, through the foaming and 3D-printing of biomimetic calcium phosphates, thereby obtaining scaffolds with controlled micro- and nanoporosity and with tailored macropore architectures. Calcium-deficient hydroxyapatite (CDHA) scaffolds were evaluated after 6 and 12 weeks in an ectopic-implantation canine model and compared with two sintered ceramics, biphasic calcium phosphate and β-tricalcium phosphate. Only foams with spherical, concave macropores and not 3D-printed scaffolds with convex, prismatic macropores induced significant ectopic bone formation. Among them, biomimetic nanostructured CDHA produced the highest incidence of ectopic bone and accelerated bone formation when compared with conventional microstructured sintered calcium phosphates with the same macropore architecture. Moreover, they exhibited different bone formation patterns; in CDHA foams, the new ectopic bone progressively replaced the scaffold, whereas in sintered biphasic calcium phosphate scaffolds, bone was deposited on the surface of the material, progressively filling the pore space. In conclusion, this study demonstrates that the high reactivity of nanostructured biomimetic CDHA combined with a spherical, concave macroporosity allows the pushing of the osteoinduction potential beyond the limits of microstructured calcium phosphate ceramics.

Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization. We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation. The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs. The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation.

A quantitative approach for analysing bone modelling patterns from craniofacial surfaces in hominins.

Bone size and shape arise throughout ontogeny as a result of the coordinated activity of osteoblasts and osteoclasts, responsible for bone deposition and resorption, and growth displacements. The modelling processes leave specific microstructural features on the bone surface, which can be used to infer the mechanisms shaping craniofacial traits in extinct and extant species. However, the analysis of bone surfaces from fossils and archaeological samples faces some difficulties related to the bone loss caused by taphonomic factors, and the lack of formal methods for estimating missing information and comparing the patterns of bone modelling among several specimens and samples. The present study provides a new approach for the quantitative analysis of bone formation and resorption patterns obtained from craniofacial surfaces. First, interpolation techniques were used to estimate missing data on high-resolution replicas of the left maxilla in a sample of sub-adult and adult modern humans and sub-adult fossil hominins. The performance of this approach was assessed by simulating variable amounts of missing data. Then, we applied measures of dispersion and central tendency to represent the variation and average pattern of bone modelling within samples. The spatial interpolation resulted in reliable estimations of the type of cell activity (deposition or resorption) in the missing areas, even when large extensions of the bone surface were lost. The quantification of the histological data allowed us to integrate the information of different specimens and depict the areas with higher and lower variation in the bone modelling pattern of the maxilla among specimens. Overall, the main advantages of the quantitative approach used here for generating bone modelling patterns are the high replicability and the possibility of incorporating variation among specimens into the comparisons among samples.

Effect of Serial Use of Bone Morphogenetic Protein 2 and Fibroblast Growth Factor 2 on Periodontal Tissue Regeneration.

This study evaluates the synergistic effect of serial application of bone morphogenetic protein 2 (BMP2) and fibroblast growth factor 2 (FGF2) on both new bone formation and periodontal tissue regeneration using 1-wall intrabony defect in mongrel dogs. One-wall defects were created at the mesial aspect of the mandibular first molars of 6 male mongrel dogs. Each mandibular defect received 1 of the 2 experimental treatments randomly (BMP2 or BMP2 + FGF2), and it was allowed to heal for either 4 or 8 weeks postoperatively. Histologic and histomorphometric analyses were performed for the evaluation of the overall healing patterns of new bone formation and periodontal tissue regeneration. The results showed that after 8 weeks, serial application of BMP2 and FGF2 significantly improved the periodontal tissue regeneration, whereas application of BMP2 only showed greater new bone formation after 4 weeks. The serial application of BMP2 and FGF2 may have synergistic effects on periodontal tissue regeneration over time.

Host cell recruitment patterns by bone morphogenetic protein-2 releasing hyaluronic acid hydrogels in a mouse subcutaneous environment.

This study aimed to identify host cell recruitment patterns in a mouse model in response to rhBMP-2 releasing hyaluronic acid hydrogels and influence of added nano-hydroxyapatite particles on rhBMP-2 release and pattern of bone formation. Implanted gels were retrieved after implantation and cells were enzymatically dissociated for flow cytometric analysis. Percentages of macrophages, progenitor endothelial cells and putative mesenchymal stem cells were measured. Implants were evaluated for BMP-2 release by ELISA and by histology to monitor tissue formation. Hyaluronic acid+BMP-2 gels influenced the inflammatory response in the bone healing microenvironment. Host-derived putative mesenchymal stem cells were major contributors. Addition of hydroxyapatite nanoparticles modified the release pattern of rhBMP-2, resulting in enhanced bone formation.

Assessment of bone repair in critical-size defect in the calvarium of rats after the implantation of tricalcium phosphate beta (β-TCP)

ObjectivesEvaluating the osteoconductive property of tricalcium phosphate beta (β-TCP) in comparison to that of inorganic bovine bone for repair in a critical-size defect in the rat calvarium.Materials and MethodsCritical-size defects of 7mm were made with a trephine in the calvaria of 48 Wistar rats. The animals were divided into four groups, and the defects in each group were filled with tricalcium phosphate beta (β-TCP), inorganic bovine bone (Bio-Oss), autogenous bone, or left empty. The animals were euthanized at two different time points (30 and 60days post-operation). All defects were recovered with a absorbable membrane of bovine cortical bone. Histological, histometric, and immunohistochemical (osteocalcin) assessments were carried out at 30 and 60days post-operation. ResultsAt 30days post-operation, all groups showed areas of bone formation, predominantly when autogenous grafts were used. However, there were no statistically significant differences between the treatment groups (p>0.05). After 60days, there were similarities in the bone formation patterns between the β-TCP (26.32±) and Bio-Oss (17.35±) groups (p=0.549). In terms of the immunohistochemical assessment of osteocalcin, the clot group showed light to moderate staining at 30 and 60days. The autogenous group showed moderate staining at 30days and moderate to intense staining after 60days. The Bio-Oss group showed light to moderate staining after 30days and intense staining at 60days. The β-TCP group showed moderate staining at 30 and 60days post-operation. Conclusionβ-TCP is a good osteoconductive material with similar effects to those of inorganic bovine bone graft and is suitable for utilization in the repair of bone defects.

Stretch force guides finger-like pattern of bone formation in suture.

Mechanical tension is widely applied on the suture to modulate the growth of craniofacial bones. Deeply understanding the features of bone formation in expanding sutures could help us to improve the outcomes of clinical treatment and avoid some side effects. Although there are reports that have uncovered some biological characteristics, the regular pattern of sutural bone formation in response to expansion forces is still unknown. Our study was to investigate the shape, arrangement and orientation of new bone formation in expanding sutures and explore related clinical implications. The premaxillary sutures of rat, which histologically resembles the sutures of human beings, became wider progressively under stretch force. Micro-CT detected new bones at day 3. Morphologically, these bones were forming in a finger-like pattern, projecting from the maxillae into the expanded sutures. There were about 4 finger-like bones appearing on the selected micro-CT sections at day 3 and this number increased to about 18 at day 7. The average length of these projections increased from 0.14 mm at day 3 to 0.81 mm at day 7. The volume of these bony protuberances increased to the highest level of 0.12 mm3 at day 7. HE staining demonstrated that these finger-like bones had thick bases connecting with the maxillae and thin fronts stretching into the expanded suture. Nasal sections had a higher frequency of finger-like bones occuring than the oral sections at day 3 and day 5. Masson-stained sections showed stretched fibers embedding into maxillary margins. Osteocalcin-positive osteoblasts changed their shapes from cuboidal to spindle and covered the surfaces of finger-like bones continuously. Alizarin red S and calcein deposited in the inner and outer layers of finger-like bones respectively, which showed that longer and larger bones formed on the nasal side of expanded sutures compared with the oral side. Interestingly, these finger-like bones were almost paralleling with the direction of stretch force. Inclined force led to inclined finger-like bones formation and deflection of bilateral maxillae. Additionally, heavily compressive force caused fracture of finger-like bones in the sutures. These data together proposed the special finger-like pattern of bone formation in sutures guided by stretch force, providing important implications for maxillary expansion.

Bone up: craniomandibular development and hard-tissue biomineralization in neonate mice

The presence of regional variation in the osteogenic abilities of cranial bones underscores the fact that the mechanobiology of the mammalian skull is more complex than previously recognized. However, the relationship between patterns of cranial bone formation and biomineralization remains incompletely understood. In four strains of mice, micro-computed tomography was used to measure tissue mineral density during perinatal development in three skull regions (calvarium, basicranium, mandible) noted for variation in loading environment, embryological origin, and ossification mode. Biomineralization levels increased during perinatal ontogeny in the mandible and calvarium, but did not increase in the basicranium. Tissue mineral density levels also varied intracranially, with density in the mandible being highest, in the basicranium intermediate, and in the calvarium lowest. Perinatal increases in, and elevated levels of, mandibular biomineralization appear related to the impending postweaning need to resist elevated masticatory stresses. Similarly, perinatal increases in calvarial biomineralization may be linked to ongoing brain expansion, which is known to stimulate sutural bone formation in this region. The lack of perinatal increase in basicranial biomineralization could be a result of earlier developmental maturity in the cranial base relative to other skull regions due to its role in supporting the brain’s mass throughout ontogeny. These results suggest that biomineralization levels and age-related trajectories throughout the skull are influenced by the functional environment and ontogenetic processes affecting each region, e.g., onset of masticatory loads in the mandible, whereas variation in embryology and ossification mode may only have secondary effects on patterns of biomineralization. Knowledge of perinatal variation in tissue mineral density, and of normal cranial bone formation early in development, may benefit clinical therapies aiming to correct developmental defects and traumatic injuries in the skull, and more generally characterize loading environments and skeletal adaptations in mammals by highlighting the need for multi-level analyses for evaluating functional performance of cranial bone.

The influence of collagen membrane and autogenous bone chips on bone augmentation in the anterior maxilla: a preclinical study.

To evaluate the effect of a resorbable collagen membrane and autogenous bone chips combined with deproteinized bovine bone mineral (DBBM) on the healing of buccal dehiscence-type defects. The second incisors and the first premolars were extracted in the maxilla of eight mongrels. Reduced diameter, bone-level implants were placed 5weeks later. Standardized buccal dehiscence-type defects were created and grafted at implant surgery. According to an allocation algorithm, the graft composition of each of the four maxillary sites was DBBM+membrane (group D+M), autogenous bone chips+DBBM+membrane (group A+D+M), DBBM alone (group D) or autogenous bone chips+DBBM (group A+D). Four animals were sacrificed after 3weeks of healing and four animals after 12weeks. Histological and histomorphometric analyses were performed on oro-facial sections. The pattern of bone formation and resorption within the grafted area showed high variability among the same group and healing time. The histomorphometric analysis of the 3-week specimens showed a positive effect of autogenous bone chips on both implant osseointegration and bone formation into the grafted region (P<0.05). The presence of the collagen membrane correlated with greater bone formation around the DBBM particles and greater bone formation in the grafted region after 12weeks of healing (P<0.05). The oro-facial width of the augmented region at the level of the implant shoulder was significantly reduced in cases where damage of the protection splints occurred in the first week of healing (P<0.05). The addition of autogenous bone chips and the presence of the collagen membrane increased bone formation around DBBM particles. Wound protection from mechanical noxa during early healing may be critical for bone formation within the grafted area.

Delivery vehicle effects on bone regeneration and heterotopic ossification induced by high dose BMP-2.

Alginate hydrogel-based BMP-2 delivery has induced better spatiotemporal bone regeneration in animals, compared to clinically used collagen sponge, at lower BMP-2 doses. Lack of clear dose-response relationships for BMP-2 vis-à-vis bone regeneration has contributed to the use of higher doses clinically. We investigated the potential of the alginate system, with comparatively favorable BMP-2 release-kinetics, to reduce heterotopic ossification and promote bone regeneration, when used with a high BMP-2 dose. While defect mineralization improved with alginate hydrogel, the initial high-release phase and likely early tissue exposure to BMP-2 appeared sufficient to induce heterotopic ossification. The characterization presented here should provide the framework for future evaluations of strategies to optimize bone formation and minimize adverse effects of high dose BMP-2 therapy.