RESUMEN
INTRODUCTION: The aim of this pilot study was to examine the kinetics of alterations in alveolar ridge width and height following tooth extraction with and without ridge preservation, using anorganic bovine bone mineral (ABBM) and a novel device (SocketKAP(™) ) designed for obturation of socket orifice. MATERIALS AND METHODS: Maxillary left and right PM1 and mandibular right PM2 and PM4 were extracted on six beagle dogs and treated as follows: Group A: negative control; Group B: SocketKAP(™) alone; Group C: ABBM + SocketKAP(™) . Serial cone-beam computed tomography (CBCT) was taken at 0-, 1-, 2-, 4-, 8- and 12-week intervals to calculate the rate of alveolar bone loss, followed by histologic and histomorphometric analyses at 12 weeks. Across group outcomes were compared. RESULTS: Without additional intervention, the crestal-most 3 mm of alveolar bone width lost approximately 0.21-0.28 mm per week. The rate of alveolar buccal bone height loss was 0.19 mm per week. Comparatively, in group C, the alveolar bone was relatively stable, with loss of only 0.003-0.13 mm of width and 0.12 mm of height per week. These differences were statistically significant. The alveolar bone in sites treated by SocketKAP(™) alone was significantly different from control only at select time points and locations of the ridge, presumably due to small sample size. CONCLUSION: Without additional intervention, tooth extraction was accompanied by rapid loss of alveolar ridge width and height. Applications of SocketKAP(™) and ABBM were effective in reducing alveolar crestal width and height loss following tooth extraction.
Asunto(s)
Proceso Alveolar/cirugía , Extracción Dental/efectos adversos , Pérdida de Hueso Alveolar/etiología , Pérdida de Hueso Alveolar/prevención & control , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/patología , Animales , Densidad Ósea , Tomografía Computarizada de Haz Cónico/métodos , Perros , Extracción Dental/métodosRESUMEN
Recently, we have shown that anti-BMP2 monoclonal antibodies (mAbs) can trap endogenous osteogenic BMP ligands, which can in turn mediate osteodifferentiation of progenitor cells. The effectiveness of this strategy requires the availability of the anti-BMP-2 monoclonal antibodies antigen-binding sites for anti-BMP-2 monoclonal antibodies to bind to the scaffold through a domain that will leave its antigen-binding region exposed and available for binding to an osteogenic ligand. We examined whether antibodies bound to a scaffold by passive adsorption versus through Protein G as a linker will exhibit differences in mediating bone formation. In vitro anti-BMP-2 monoclonal antibodies was immobilized on absorbable collagen sponge (ACS) with Protein G as a linker to bind the antibody through its Fc region and implanted into rat calvarial defects. The biomechanical strength of bone regenerated by absorbable collagen sponge/Protein G/anti-BMP-2 monoclonal antibodies immune complex was compared to ACS/anti-BMP-2 monoclonal antibodies or ACS/Protein G/isotype mAb control group. Results demonstrated higher binding of anti-BMP-2 monoclonal antibodies/BMPs to C2C12 cells, when the mAb was initially attached to recombinant Protein G or Protein G-coupled microbeads. After eight weeks, micro-CT and histomorphometric analyses revealed increased bone formation within defects implanted with absorbable collagen sponge/Protein G/anti-BMP-2 monoclonal antibodies compared with defects implanted with absorbable collagen sponge/anti-BMP-2 monoclonal antibodies (p < 0.05). Confocal laser scanning microscopy (CLSM) confirmed increased BMP-2, -4, and -7 detection in sites implanted with absorbable collagen sponge/Protein G/anti-BMP-2 monoclonal antibodies in vivo. Biomechanical analysis revealed the regenerated bone in sites with Protein G/anti-BMP-2 monoclonal antibodies had higher mechanical strength in comparison to anti-BMP-2 monoclonal antibodies. The negative control group, Protein G/isotype mAb, did not promote bone regeneration and exhibited significantly lower mechanical properties (p < 0.05). Altogether, our results demonstrated that application of Protein G as a linker to adsorb anti-BMP-2 monoclonal antibodies onto the scaffold was accompanied by increased in vitro binding of the anti-BMP-2 mAb/BMP immune complex to BMP-receptor positive cell, as well as increased volume and strength of de novo bone formation in vivo.
Asunto(s)
Implantes Absorbibles , Anticuerpos Inmovilizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Proteína Morfogenética Ósea 2/inmunología , Regeneración Ósea/efectos de los fármacos , Cráneo/efectos de los fármacos , Cráneo/fisiología , Animales , Anticuerpos Inmovilizados/administración & dosificación , Anticuerpos Inmovilizados/inmunología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/inmunología , Línea Celular , Colágeno/química , Femenino , Ratones , Ratas Sprague-Dawley , Cráneo/inmunología , Cráneo/lesionesRESUMEN
Biomaterials are widely used as scaffolds for tissue engineering. We have developed a strategy for bone tissue engineering that entails application of immobilized anti-BMP-2 monoclonal antibodies (mAbs) to capture endogenous BMPs in vivo and promote antibody-mediated osseous regeneration (AMOR). The purpose of the current study was to compare the efficacy of immobilization of a specific murine anti-BMP-2 mAb on three different types of biomaterials and to evaluate their suitability as scaffolds for AMOR. Anti-BMP-2 mAb or isotype control mAb was immobilized on titanium (Ti) microbeads, alginate hydrogel, and ACS. The treated biomaterials were surgically implanted in rat critical-sized calvarial defects. After 8 weeks, de novo bone formation was assessed using micro-CT and histomorphometric analyses. Results showed de novo bone regeneration with all three scaffolds with immobilized anti-BMP-2 mAb, but not isotype control mAb. Ti microbeads showed the highest volume of bone regeneration, followed by ACS. Alginate showed the lowest volume of bone. Localization of BMP-2, -4, and -7 antigens was detected on all 3 scaffolds with immobilized anti-BMP-2 mAb implanted in calvarial defects. Altogether, these data suggested a potential mechanism for bone regeneration through entrapment of endogenous BMP-2, -4, and -7 proteins leading to bone formation using different types of scaffolds via AMOR.