Bone regeneration using recombinant human bone morphogenetic protein-2 (rhBMP-2) in alveolar defects of primate mandibles

The efficacy of bone morphogenetic protein (BMP) for bone reconstruction has been widely studied in numerous animal experiments, but insufficient information exists about its ability to regenerate bone in primates. The purpose of this study was to evaluate the effects of recombinant human BMP-2 (rhBMP-2) on bone formation in alveolar bone defects in the mandibles of young primates. Marginal bone defects were created in the mandibles of nine 5-year-old rhesus monkeys and rhBMP-2 permeated in a polylactic-co-glycolic acid-coated gelatin sponge (PGS) was implanted into the bone defects. The resected bone treated with rhBMP-2 regenerated completely at 12 weeks postoperatively, and remodelling and consolidation of new bone were seen histologically. This study provides evidence of considerable bone regeneration in alveolar defects after surgical implantation of rhBMP-2 in non-human primates. This technique may be an effective alternative to autogenous bone grafts for reconstructive surgery in clinical practice.     

Scientific evidence on the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in oral and maxillofacial surgery

Purpose

This study aimed to identify the main indications for the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) for bone repair and maintenance in the maxilla and mandible through a review of clinical trials evaluating the viability of using rhBMP-2 to delay the installation of dental implants, thus allowing satisfactory bone formation and long-term osseointegration.

Methods

Literature search of the PubMed/Medline databases was performed using the following MeSH index terms—“bone morphogenetic protein 2” and “dentistry”. Only clinical trials necessarily published in English, related to dentistry, and focused on bone reconstruction in critical defects, post-extraction alveoli, increasing the atrophic alveolar ridge, or surgery for maxillary sinus elevation were included, regardless of the age, sex, ethnicity, associated morbidities, or period of publication.

Results

Of the 17 studies identified based on the search filters, 2 were excluded. Therefore, 15 studies were finally included in this review.

Conclusions

Based on the results of our review, we concluded that the use of rhBMP-2 for the preservation of the alveolar ridge after tooth extraction or for increasing the local defects is safe and viable. The use of rhBMP-2/Bio-Oss® for the elevation of the maxillary sinus membrane is unnecessary; however, it can improve and accelerate the maturation process in cases of guided bone regeneration in peri-implant defects. Compounds comprising rhBMP-2, allogenic bone, and plasma-rich platelet (PRP) can act as autograft substitutes in mandibular critical defects.

     

Effect of recombinant human bone morphogenetic protein-2 on mandibular distraction osteogenesis

The purpose of this investigation was to study the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone formation of mandibular distraction osteogenesis. Six skeletally mature sheep underwent 10 mm of bilateral mandibular distraction osteogenesis via a custom-made distractor. Three micrograms of rhBMP-2 with a collagen carrier was implanted in the osteotomy site of one side of the mandible during the osteotomy phase. The contralateral side was used as the control group, and no material was implanted into the distracted area. At 10 days after the end of distraction, all animals were killed, and the distracted calluses were harvested for radiologic and histologic analysis. New bone was generated in the distracted zone in all groups. Histologic and radiologic examination showed that the new bone formation was greater in the rhBMP-2 group than in the control group. Quantitative computed tomography evaluation, however, did not demonstrate a significantly different mean bone density of the regenerates between the 2 groups. The results indicate that application of a rhBMP-2/collagen implant during the osteotomy phase of distraction osteogenesis increased bone formation but did not have a significant effect on bone density of the regenerates.     

Recombinant human bone morphogenetic protein-2 stimulation of bone formation around endosseous dental implants

BACKGROUND: Successful endosseous implant placement requires that the implant be stable in alveolar bone. In certain cases, the implant can be stabilized in native bone but some part of the implant is not covered by bone tissue. This often occurs during placement of implants into extraction sites or in areas where bone resorption has occurred and the ridge width is not sufficient to completely surround the implant. In those cases, the clinician usually employs a procedure to encourage bone formation. These procedures typically include a bone graft and/or membrane therapy. Recent advances have led to the isolation, cloning, and production of recombinant human proteins that stimulate bone formation. One of these bone morphogenetic proteins (rhBMP-2) has been extensively studied in animal models and is currently being tested in human clinical trials. METHODS: In this study, rhBMP-2 was tested using a collagen sponge carrier to stimulate bone formation in defects in the canine mandible around endosseous dental implants. Six animals had a total of 48 implants placed. rhBMP-2 with the collagen carrier was implanted around 24 of these, the remainder having only the collagen carrier placed. Half the sites were covered with a nonresorbable expanded polytetrafluoroethylene membrane. Histologic analysis was performed after 4 and 12 weeks. The area of new bone formed, percentage of bone-to-implant contact in the defect area, and percentage fill of the defect was calculated. RESULTS: The addition of rhBMP-2 resulted in significantly greater amounts of new bone area and percentage of bone-to-implant contact and with more percentage fill after 4 and 12 weeks of healing. The area of new bone formed was reduced after 4 weeks when a membrane was present but after 12 weeks, there was no significant difference between membrane and non-membrane treated sites. In some specimens, new bone was found coronal to the membranes, with rhBMP-2-treated sites having greater amounts than non-rhBMP-2-treated sites. CONCLUSIONS: These data demonstrate that a bone differentiation factor significantly stimulates bone formation in peri-implant bone defects in the canine mandible. In addition, bone-to-implant contact was significantly enhanced along the rough implant surface. Membrane-treated sites had less new bone formation after 4 weeks of healing but were similar to non-membrane sites after 12 weeks. These results demonstrate that rhBMP-2 can be used to stimulate bone growth both around and onto the surface of endosseous dental implants placed in sites with extended peri-implant osseous defects.     

Recombinant human bone morphogenetic protein-2 for peri-implant bone regeneration: a case report

Background: Currently, clinicians have a limited treatment arsenal in the repair of peri‐implant defects. The aim of the present report is to present the clinical results of treating a dental implant using recombinant human bone morphogenetic protein (rhBMP)‐2 in an elderly patient. Methods: A 75‐year‐old man presented for routine dental prophylaxis. Clinical and radiographic examination revealed significant loss of attachment and bone loss around an implant replacing the maxillary left first molar. The patient did not report any symptoms, and the implant showed no signs of mobility. Because of the severity of the defect, regenerative treatment using a combination of rhBMP‐2 and freeze‐dried bone allograft was used. Results: The patient was followed for 80 weeks postoperatively. By 28 weeks, significant probing depth reduction and radiographic bone fill was observed, and the original implant crown was replaced. From 28 weeks postoperatively to 80 weeks, no significant clinical or radiographic changes were observed. Conclusions: rhBMP‐2 represents a potential therapeutic modality for severe peri‐implant hard tissue loss. Future studies should examine parameters, such as surgical technique, to maximize the rhBMP‐2‐driven regenerative outcomes.     

Prefabrication of vascularized bone flap induced by recombinant human bone morphogenetic protein 2 (rhBMP-2)

An experimental model for the prefabrication of a vascularized bone flap was developed in this study. To form vascularized bone in the desired configuration and to increase the survival rate of the grafted bone, a muscle vascularized pedicle (MVP) was transformed into vascularized bone by the inducer recombinant human bone morphogenetic protein 2 (rhBMP-2). The muscle flap (8 x 8 mm) raised on saphenous vessels in the rat thigh was sandwiched between same-size collagen (Terudermis) sheets in the presence or absence of impregnated 25 microg of rhBMP-2 for the experimental group and the control group, respectively. The flaps were harvested 1, 2 and 3 weeks postoperatively. Bone transformation was detected by gross examination, radiology, and histologic testing. No evidence of muscle tissue transformation was found in control flaps, whereas all of the experimental flaps produced new bone. Saphenous vessels were observed to supply the new bone upon harvesting, and the newly formed vascularized bone showed good configuration with shape of the Terudermis sheet. This study indicates that this model of effective bone reconstruction could be potentially applied in a therapeutic setting.     

In situ osteogenesis: regeneration of 10-cm mandibular defect in porcine model using recombinant human bone morphogenetic protein-2 (rhBMP-2) and Helistat absorbable collagen sponge

Traditional bone grafting relies upon the incorporation of a bone-cell bearing structure into a recipient site. The graft serves as a scaffold that is eventually replaced and remodeled. This process is known as osteoconduction. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is commercially available as an acellular implant in which the protein is bound to an absorbable collagen sponge (ACS). The rhBMP-2/ACS implant converts undifferentiated mesenchymal stem cells into osteoblasts and promotes an intense local neovascular response. This process, known as osteoinduction, produces bone via membranous, chondroid, or endochondral ossification. The type of bone synthesis depends upon the mesenchymal substrate and the local cellular environment. Using this simple technique, bone defects can be resynthesized with good outcomes and a significant reduction in donor site morbidity. Repair of a critical-sized mandibular resection defect with ISO is described. Basic science concepts of rhBMP-2, relevant histopathologic findings, and clinical application are described.     

Effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on bone consolidation on distraction osteogenesis: a preliminary study in rabbit mandibles.

AIM: To examine the effectiveness of administering recombinant human bone morphogenetic protein-2 (rhBMP-2) in distraction osteogenesis. MATERIAL AND METHODS: Twenty-one mature male Japanese white rabbits underwent unilateral mandibular osteotomy. After 5 days, the osteotomized mandibles were distracted 1mm/day for 10 days. On the first day (groups A-1 [n=4] and A-2 [n=4]) or on the last day (group B [n=5]) of distraction, rhBMP-2 mixed with collagen gel was injected into the distraction zone. In control groups (groups C-1 [n=4] and C-2 [n=4]), the mandibles were distracted without rhBMP-2 injection. At the end of the distraction period (groups A-1 and C-1) and after 2 weeks of consolidation (groups A-2, B, and C-2), the distracted mandibles were harvested and examined with soft radiographs, peripheral quantitative computed tomography (pQCT), and microscopy. RESULTS: Radioopacity was more marked in the distraction zone of the groups with rhBMP-2 than in control groups. The mineral density of the cortical bone (BMD) was higher in groups B and A-2 than in group C-2. Histologically, bone formation was more advanced in groups A-2 and B than in group C-2. The cortical BMD was higher in group A-1 than in group C-1. Histologically, bone formation was more advanced in groups A-2 and B than in group C-2. CONCLUSION: These results suggest that rhBMP-2 promotes bone formation in distraction osteogenesis.     

Formation and resolution of ankylosis under application of recombinant human bone morphogenetic protein-2 (rhBMP-2) to class III furcation defects in cats

OBJECTIVES: Periodontal regeneration under application of bone morphogenetic protein (BMP) is compromised by ankylosis. Ankylosis disappearance following application of BMP has been observed in the case of a small defect, which might be beneficial change for periodontal regeneration. However, the histological observation of ankylosis disappearance has not been demonstrated in a large defect. The purpose of this present study was to confirm resolution of ankylosis during periodontal regeneration by recombinant human BMP-2 (rhBMP-2) applied to class III furcation defects. MATERIAL AND METHODS: Class III furcation defects were created in the premolars of six adult cats. The rhBMP-2 material, prepared by applying rhBMP-2 to a combination of polylactic acid-polygricolic copolymer and gelatin sponge (PGS; 0.33 microg rhBMP-2/mm(3) PGS) or control material containing only PGS, was implanted into each defect. The cats were killed at 3, 6 or 12 weeks after surgery and serial sections were prepared for histological and histometrical observation. RESULTS: Ankylosis was observed in some of the rhBMP-2/PGS group at 3 and 6 weeks, but not at 12 weeks. At 6 weeks, osteoclast-like cells were visible in the rhBMP-2/PGS group with ankylosis. Residual PGS was evident between the bone and root surface in the rhBMP-2/PGS group without ankylosis at 3 weeks. CONCLUSIONS: Resolution of ankylosis by osteoclast-like cells possibly occurred under application of rhBMP-2. Residual PGS might play an important role in preventing ankylosis formation.     

Recombinant human bone morphogenetic protein-2 stimulates osteoblastic differentiation in cells isolated from human periodontal ligament.

Periodontal ligament cells may play an important role in the successful regeneration of the periodontium. We investigated the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2), one of the most potent growth factors that stimulates osteoblast differentiation and bone formation, on cell growth and osteoblastic differentiation in human periodontal ligament cells (HPLC) isolated from four adult patients. rhBMP-2 induced no significant changes in cell growth in any of the HPLCs. rhBMP-2 at concentrations over 50 ng/mL significantly stimulated alkaline phosphatase (ALPase) activity and parathyroid hormone (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation, which are early markers of osteoblast differentiation, in the HPLCs. rhBMP-2 (500 ng/mL) also slightly enhanced the level of PTH/PTH-related peptide receptor mRNA expression in these cells. While interleukin-1 beta enhanced ALPase activity stimulated with rhBMP-2, tumor necrosis factor-alpha inhibited the rhBMP-2-stimulated activity. Interleukin-6 induced no significant changes in ALPase activity stimulated with rhBMP-2. Although HPLCs, whether treated with rhBMP-2 or not, could not produce measurable amounts of osteocalcin, which is a marker of more mature osteoblasts, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] induced osteocalcin mRNA expression and protein synthesis in these cells. rhBMP-2 inhibited 1,25(OH)2D3-induced osteocalcin synthesis in HPLCs at both the mRNA and protein levels. These results suggest that rhBMP-2 provides an anabolic effect on periodontal regeneration by stimulation of osteoblastic differentiation in human periodontal ligament cells, and that this stimulatory effect is differentially modulated by inflammatory cytokines during the course of periodontal regeneration.     

Potential of recombinant human bone morphogenetic protein-2 in bone regeneration

Recombinant human bone morphogenetic protein (rhBMP-2) has been used as a bone substitute. This article describes the rhBMP-2 structure, mechanisms of action, carriers, advantages, safety, and recent clinical studies relevant to dentistry.     

Effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of periodontal attachment following tooth replantation in dogs

OBJECTIVES: Subcutaneous and intramuscular implants of bone morphogenetic protein-12 (BMP-12) have been shown to induce formation of tendon and ligament tissue. BMP-12 induced a new attachment with a distinct fibrocartilaginous zone at the tendon-bone interface in the rat tendon-bone attachment model. Surgical controls showed poor healing and failure to reform the appropriate tendon-bone attachment morphologically. Application of recombinant human BMP-12 (rhBMP-12) to periodontal defects suggests that rhBMP-12 has the potential to support regeneration of the periodontal ligament (PDL). The objective of this pilot study was to evaluate this effect of rhBMP-12 in a tooth replantation model. METHODS: Six, young adult, male Hound Labrador mongrel dogs were used. Maxillary and/or mandibular incisor and premolar teeth were extracted and the PDL was either left "intact" or removed by root planing. rhBMP-12 (1.0 mg/ml) or a buffer control was topically applied to teeth with "intact" PDL in contralateral jaw quadrants in each of 3 animals. The teeth were immersed in 1.0 ml of the rhBMP-12 or the buffer solution for 10 min and then replanted. The remaining three animals received rhBMP-12 (1.0 mg/ml) and the buffer control in a similar fashion applied to teeth instrumented to remove the PDL and cementum, and surface demineralized with citric acid. The animals were euthanized at 8 weeks postsurgery and block sections were collected and processed for histopathologic analysis. RESULTS: No dramatic differences were found between teeth receiving topical rhBMP-12 and the buffer control. Application of rhBMP-12 did not have an apparent effect on new cementum and PDL formation in the tooth replantation model. Moreover, application of rhBMP-12 did not increase nor did it decrease the apparent presence and extent of ankylosis along the root surface compared to the control. CONCLUSIONS: The observations from this study do not support the use of topical rhBMP-12 to support the reestablishment of the PDL including regeneration of cementum and functionally oriented fibers, and to prevent ankylosis and root resorption following replantation of teeth.     

Effect of recombinant human bone morphogenetic protein-2/absorbable collagen sponge (rhBMP-2/ACS) on healing in 3-wall intrabony defects in dogs

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) in an absorbable collagen sponge (ACS) carrier is being evaluated as a candidate therapy for periodontal regeneration. The objective of this study was to evaluate regeneration of alveolar bone and cementum, and associated root resorption and ankylosis following surgical implantation of rhBMP-2/ACS in a canine clinical model. METHODS: Bilateral 3-wall intrabony periodontal defects were surgically induced in the premolar region in the maxilla and mandible in 8 young adult Korean mongrel dogs. The defects in each animal received rhBMP-2/ACS (rhBMP-2 at 0.2 mg/ml, total implant volume/defect approximately 0.1 ml) or buffer/ACS, or served as sham-operated controls. Surgeries were sequenced for each animal to provide postmortem observations following 8- and 24-week healing intervals. Treatment outcomes were evaluated using clinical, radiographic, and histometric parameters. RESULTS: Surgical implantation of rhBMP-2/ACS resulted in accelerated enhanced bone formation in the 3-wall intrabony periodontal defects but in no apparent enhancement of cementum regeneration. rhBMP-2/ACS did not appear to be associated with aberrant healing events such as root resorption and ankylosis under these simulated clinical conditions. CONCLUSIONS: Surgical implantation of rhBMP-2/ACS may be used safely to support regeneration of alveolar bone in intrabony periodontal defects in dogs without aberrant events such as root resorption or ankylosis complicating the regenerative procedure. rhBMP-2/ACS does not appear to have a significant effect on cementum regeneration and formation of a functional periodontal ligament in this model.     

下颌骨切除骨缺损修复术后的X线影像分析

目的 :观察下颌骨切除骨缺损修复术后X线影像特点。方法 :对下颌骨良性肿瘤切除骨缺损修复术后的42例病例的X线影像分析。结果 :骨性愈合 31例 ;植入骨吸收 5例 ;植入块断裂 6例。结论 :曲面断层和下颌骨侧位应作为术后必备的片位 ;术后 1～ 2周、3～ 6月、1年以后作为随访的三个阶段 ,能较准确地观察术后愈合情况     

Expression of bone morphogenetic protein in the course of osteoinduction by recombinant human bone morphogenetic protein-2

To clarify the mechanism of osteoinduction by recombinant human bone morphogenetic protein-2 (rhBMP-2), we examined the time-course localization of bone morphogenetic proteins (BMPs) immunostained by an anti-BMP-2 monoclonal antibody after implantation of pellets consisting of rhBMP-2 and collagen in rat calf muscle pouch. On day 3 after implantation, BMP was detected in the entire lump, and the intensity of staining for BMP around the implant on day 7 was weaker than that on day 3. The staining for BMP decreased with time and the region of staining for BMP remained more centralized in the implant. On day 10 after implantation, BMP was observed in part of the newly induced cartilage, especially around chondrocytes. On day 14 after implantation, BMP was localized in the newly induced woven bone. On day 21, BMP staining was found in osteoblasts at the surface of the newly induced bone. Especially, the staining for BMP decreased from day 10 to day 21. These results indicate that the woven bone was replaced with mature lamellar bone from day 14 to day 21. The present findings suggest that rhBMP-2 plays an important role in osteoinduction, especially at the early stage.     

Enhancement by recombinant human bone morphogenetic protein-2 of bone formation by means of porous hydroxyapatite in mandibular bone defects.

Hydroxyapatite is osteoconductive and can maintain an original biocompatible form. It is useful, in the reconstruction of bone defects, to enhance the osteoconduction of hydroxyapatite with an osteogenic protein. The aim of this study was to evaluate the bone formation in surgically created defects of rabbit mandibles by a combination of recombinant human bone morphogenetic protein-2 (rhBMP-2), with porous hydroxyapatite and atelopeptide type I collagen used as the carrier for rhBMP-2. A 10-microg rhBMP-2-implanted group (n = 15) and a control group (n = 15), in which only atelopeptide type I collagen and porous hydroxyapatite were implanted, were histologically examined 3, 7, and 21 days after implantation. The alkaline phosphatase activity was also quantitatively analyzed. No new bone formation was observed in either the tested or the control group after 3 days. At 7 days, immature bone tissue was observed in some pores of the rhBMP-2implanted group, while in the control group, immature mesenchymal cells were observed. At 21 days, trabecular bone lined some pore walls. In the central portion, the bone marrow, including angioid tissue, was observed. New trabecular bone formation was observed on portions of the external surface of the hydroxyapatite disk. On the other hand, the control group showed infiltration of immature mesenchymal cells into some pores. Marginal bone formation was found in the pores close to the surface of the disk which opposed mandibular bone. The control group showed a slow, small increase in alkaline phosphatase activity in this study, while the experimental group showed a marked increase at 21 days. This increase was significantly higher in the tested group than in the control group at both 7 and 21 days. The findings indicate that rhBMP-2 accelerated bone formation by osteoconduction from porous hydroxyapatite. The combination of rhBMP-2, atelopeptide type I collagen, and porous hydroxyapatite is suggested to be advantageous for clinical application in reconstructing mandibular bone defects.     

Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment

OBJECTIVES: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to stimulate alveolar bone and cementum formation in periodontal defects but not a functionally oriented periodontal ligament (PDL). Subcutaneous and intramuscular implants of BMP-12 have been shown to induce tendon formation and ligament-like tissue. The objective of this study was to evaluate rhBMP-12 for periodontal regeneration, in particular PDL formation. METHODS: Six young adult Hound Labrador mongrel dogs were used. Routine supraalveolar periodontal defects were created around the mandibular premolar teeth. Three animals received rhBMP-12(0.04 mg/ml) in an absorbable collagen sponge (ACS) carrier vs. rhBMP-12(0.2 mg/mL)/ACS in contralateral defects. Three animals received rhBMP-12(1.0 mg/ml)/ACS vs. rhBMP-2(0.2 mg/ml)/ACS (total implant volume/defect approximately 1 ml). The animals were euthanized 8 weeks postsurgery and block biopsies were processed for histometric analysis. RESULTS: Bone regeneration appeared increased in sites receiving rhBMP-2/ACS compared to sites receiving rhBMP-12/ACS. Cementum regeneration was similar comparing sites implanted with rhBMP-2/ACS to sites implanted with rhBMP-12/ACS. In contrast, sites receiving rhBMP-12/ACS exhibited a functionally oriented PDL bridging the gap between newly formed bone and cementum whereas this was a rare observation in sites receiving rhBMP-2/ACS. Ankylosis appeared increased in sites receiving rhBMP-2/ACS compared to those receiving rhBMP-12/ACS. CONCLUSIONS: The outcomes of this study suggest that rhBMP-12 may have significant effects on regeneration of the PDL. Additional preclinical evaluation is needed to confirm these initial observations prior to clinical application.     

Repair of alveolar clefts with recombinant human bone morphogenetic protein (rhBMP-2) in patients with clefts

This article demonstrates the feasibility of using recombinant human bone morphogenetic protein (rhBMP-2) as a substitute for autogenous iliac crest bone for repair of congenital facial clefts in humans. In this series, 50 cleft sites were repaired in 43 patients using rhBMP-2 without the use of autogenous graft tissue. Successful osseous union was achieved in 49 of the 50 sites. In one patient, the graft failed to consolidate. Severe clefts were managed by combining distraction osteogenesis and rhBMP-2. Eliminating the need to harvest autogenous iliac crest bone resulted in substantial decrease in morbidity. The constructed alveolus performed clinically as normal bone and responded to natural tooth eruption and orthodontic movement. Histology of the tissue constructed showed normal, vital bone. Although additional investigation is warranted to determine the optimum protocol for the use of this material in alveolar cleft repair, the technique should be considered as a viable treatment option in cases in which avoiding iliac crest harvesting is desirable.     

Effect of recombinant human bone morphogenetic protein-2 on mandibular distraction at different rates in an experimental model

This study evaluates the effect of recombinant human (rh) bone morphogenetic protein (BMP)-2 on mandibular distraction at normal and rapid distraction rates. This study also determines the feasibility of compensating for the increased distraction rate by the addition of rhBMP-2 while maintaining the quality of the distraction regenerate. Twenty-four New Zealand white rabbits were divided into 2 groups, 1 treated at a normal distraction rate (0.9 mm/d) and the other at a rapid distraction rate (2.7 mm/d). At the end of the active distraction period, rhBMP-2 was injected into distraction regenerate, and the contralateral side was used as a control. The distraction regenerates were analyzed by plain radiography, microcomputed tomography, and mechanical testing. The results showed that rhBMP-2 can promote bone formation at both rapid and normal distraction rates. At week 2 and week 4 of consolidation, bone volumes in the BMP-injection sides were significantly higher than in the control sides, but no statistically significant difference was observed between the BMP-injection sides of the rapid and normal distraction groups. At week 8 of consolidation, mechanical testing demonstrated no significant difference of the failure load and stiffness between the BMP-injection and control sides. In conclusion, the study indicates that rhBMP-2 can enhance bone ossification at both normal and rapid distraction rates. The addition of rhBMP-2 can compensate for the rapid distraction rate in mandibular distraction osteogenesis. However, in the long term, the bone quality and stiffness of the distraction regeneration was not influenced by rhBMP-2.