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Objectives: Recent research has focused on application of growth factors such as bone morphogenetic proteins (BMPs) as alternatives to autogenous bone grafting. Two bone graft substitute bioimplants containing recombinant human BMPs (rhBMPs), Infuse (rhBMP-2) and OP-1 (rhBMP-7), are approved for human application but have never been compared side by side. The aim of this study was to provide a direct comparison of the osteoinductive activity of the 2 commercially available and approved rhBMP-containing bioimplants in their clinically available forms., Study Design: The activity of rhBMP-2 and -7 in solution were compared in vitro using the C2C12 cell-based assay. The activity of Infuse and OP-1 bioimplants containing 52.5 microg of rhBMP-2 or rhBMP-7, respectively, were compared in vivo using a mouse muscle pouch assay and analyzed by microscopic CT (microCT) and histology., Results: The in vitro results showed that rhBMP-2 stimulated greater alkaline phosphatase production than rhBMP-7 over various time points and concentrations. The in vivo results showed that OP-1 induced greater bone volume than Infuse. Both implants induced bone of equivalent quality based on microCT and histologic evaluation., Conclusion: In their clinically available forms, the rhBMP-7-containing OP-1 induced greater bone volume than the rhBMP-2-containing Infuse in the mouse muscle pouch model., (Copyright 2010 Mosby, Inc. All rights reserved.)

Objectives: The aim of this study was to assess the possible effect of hyperbaric oxygen (HBO) on the healing of critical-sized defects that were grafted with demineralized bone matrix (DBM) combined with Pluronic F127 (F127) to form a gel or putty, or a commercially available biphasic calcium phosphate (BCP), mixed either with blood or F127 to form a putty., Study Design: Twenty New Zealand White rabbits were randomly divided into 2 groups of 10 animals each. Bilateral 15-mm calvarial defects were created in the parietal bones of each animal, resulting in 40 critical-sized defects. Group I defects were grafted with either DBM putty or DBM gel. Group II defects were grafted with either BCP or BCP putty. Five animals from each group received HBO treatment (100% oxygen, at 2.4 ATA) for 90 minutes per day 5 days a week for 4 weeks. The other 5 animals in each group served as a normobaric (NBO) controls, breathing only room air. All animals were humanely killed at 6 weeks. The calvariae were removed and analyzed by micro computed tomography (mCT) and histomorphometry., Results: mCT analysis indicated a higher bone mineral content (BMC, P < .05), bone volume fraction (BVF; P < .001), and bone mineral density (BMD; P < .001) of the defects grafted with BCP rather than DBM. Furthermore, the voxels that were counted as bone had a higher tissue mineral density (TMD) in the BCP- than in the DBM-filled defects (P < .001). Histologically complete bony union over the defects was observed in all specimens. Histomorphometric analysis showed that DBM-filled defects had more new bone (P < .007) and marrow (P < .001), and reduced fibrous tissue compared with the BCP defects (P < .001) under NBO conditions. HBO treatment reduced the amount of fibrous tissue in BCP filled defects (P < .05), approaching levels similar to that in matching DBM-filled defects. HBO also resulted in a small but significant increase in new bone in DBM-grafted defects (P < .05)., Conclusion: Use of DBM or BCP promoted healing in these critical-sized defects. Hyperbaric oxygen therapy resulted in a slight increase in new bone in DBM-grafted defects and much larger reduction in fibrous tissue and matching increases in marrow in BCP-grafted defects, possibly through increased promotion of angiogenesis., (Copyright 2010 Mosby, Inc. All rights reserved.)

Purpose: The limitations and morbidity associated with autogenous bone grafting have driven the search for predictable bone substitutes and bioimplants. A novel method of reconstruction was tested in this case series., Materials and Methods: Ten patients with major mandibular defects following resection of biopsy-proven ameloblastoma lesions or osteomyelitis of the mandibular body or ramus were included in this study. The resection defects were spanned with rigid reconstruction plates to hold the remaining mandibular segments in the correct position. The defects were filled with a bioimplant containing bone morphogenetic protein-7 (BMP-7) in a demineralized bone matrix (DBM) suspended in a reverse-phase medium to effect sustained BMP delivery., Results: The postoperative course for all 10 patients was uneventful. Radiographic evidence of mandibular bone formation was found in all cases. At the end of 1 year, functional and esthetic reconstruction of the mandible was complete., Conclusion: Bioimplants containing BMP-7 in DBM suspended in a reverse phase medium were successful in restoring major mandibular defects in nonirradiated beds in this series of 10 patients.

Calcium phosphates like hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP), and their mixtures (biphasic calcium phosphates; BCP) are used clinically to repair bone defects. These materials can be difficult to handle and have no inherent biological activity. Handling properties of other bone substitute materials have been improved by combining them with an inert carrier such as Pluronic F-127 (Pluronic, BASF, Mt. Olive, NJ), while the addition of bone morphogenetic proteins (BMP) with such implants has also been shown to enhance bone repair. This study assessed the impact of adding Pluronic and BMPs to an HA (C-Graft) or a BCP (80/20 HA/beta-TCP ratio; Algisorb) implant's ability of promote bony repair in the rabbit calvarial defect model.Twenty-five New Zealand white rabbits were divided into 5 groups of 5 animals each. Bilateral calvarial defects were made in the parietal bones of each animal. HA or BCP alone or combined with Pluronic and/or BMP were implanted into the defect sites. Animals were euthanized at 6 weeks, postoperatively. Bone regeneration was evaluated quantitatively by histomorphometry. The amount of bone regeneration, which occurred in defects containing HA and BCP, was similar over the time period studied. Incorporating Pluronic increased handling and moldability without compromising osteoconductivity of either calcium phosphate. The addition of BMP significantly increased the amount of new bone formed with all calcium phosphates studied (P < 0.05). These results suggest that Pluronic can be added to calcium phosphates to enhance handling and moldability without any negative effects on their biocompatibility and that healing can be enhanced with the incorporation of BMPs.

Bioimplants containing bone morphogenetic proteins (BMP) such as demineralized bone matrix (DBM) are used clinically to repair bone defects because of their ability to stimulate bone regeneration. Because of handling issues, DBM granules are often combined with an inert carrier, which reduces the DBM content to 40% or less by volume. Recently, Accell DBM100 (Accell, IsoTis OrthoBiologics, Irvine, CA) has been developed, which uses processed DBM as the carrier, resulting in a DBM content of 100%. The purpose of this investigation was to evaluate the use of Accell for bone defect healing.Forty-two athymic male rats were divided into three groups. Bilateral 5 mm calvarial defects were created in each animal. In group 1, one defect was filled with Accell and the other defect was left unfilled (control). In group 2, one defect was filled with OP-1 putty (recombinant human BMP-7 and type I collagen), and the other was left unfilled. In group 3, one defect was filled with Accell and the other with OP-1. Animals were sacrificed at 4 and 8 weeks, postoperatively. Specimens were analyzed by histomorphometry to evaluate bone regeneration quantitatively. Accell and OP-1 both induced significantly more bone at 4 and 8 weeks compared with the unfilled contralateral defects. OP-1-filled defects produced significantly more total reparative tissue (bone + marrow) compared with Accell (P < 0.01); however, the increase in new bone did not reach significance at either time (P = 0.06 at 4 wk; P = 0.10 at 8 wk). In conclusion, these results suggest that Accell DBM100 will be useful in repairing craniofacial bone defects clinically.

This study evaluated the repair of critical-sized cranial vault defects in thirty New Zealand white rabbits using various allogeneic and alloplastic bone substitutes designed to provide mechanical protection to the brain as well as osteoinductivity. The strategies employed included demineralized bone matrix (DBM), a putty used in combination with a rigid resorbable plating system as a protective covering and calcium phosphate cement (CPC) combined with native partially purified bone morphogenetic protein (BMP). Bilateral critical-sized defects measuring 15 mm in diameter were created in the parietal bones of 30 adult male New Zealand white rabbits. They were divided into three groups with ten animals in each. Group 1 had one defect left unfilled as a control while autogenous bone was placed in the defect on the other side. In Group 2 a rigid resorbable copolymer membrane, Lactosorb (Lorenz Surgical, Jacksonville, Florida), was placed over both defects to cover them and protect the underlying tissues. The pericranial aspect of one defect was left unfilled while the other defect was filled with DBM putty. Group 3 had a CPC, Mimix (Lorenz Surgical, Jacksonville, Florida), placed into one of the defects while the defect on the other side was filled with the same CPC in combination with BMP in a concentration of 25 mg/mL. Bone healing was assessed clinically, radiographically, and histomorphometrically. All unfilled controlled defects, the defects covered with the resorbable Lactosorb membrane and those filled with calcium phosphate cement alone, healed with a fibrous scar. Defects reconstructed with DBM putty in combination with the resorbable Lactosorb membrane and calcium phosphate in combination with BMP healed with bone bridging the entire defect. This was obvious radiographically where the defects appeared completely filled with a dense radiopaque tissue. Histological analysis demonstrated that specimens where DBM putty was used in combination with the resorbable Lactosorb membrane had 67.7% new bone fill at 6 weeks and 84.0% at 12 weeks. Resorption of DBM particles was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. In the calcium phosphate groups where BMP was added to the bioimplant there was 45.8% new bone formation at 12 weeks. The utilization of a composite consisting of DBM with resorbable Lactosorb membrane or a composite of calcium phosphate cement composite with BMP promoted complete closure of critical-sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks. The complete bone bridging observed with these composites suggests that they could be used to enhance the protection of intracranial contents following craniofacial surgical procedures.

Purpose: The purpose of this investigation was to assess bone regeneration in critical sized defects in the rabbit calvarium using allogeneic and alloplastic bone substitutes., Materials and Methods: Thirty New Zealand White rabbits were divided into 3 groups of 10 animals each. Bilateral 15 mm x 17 mm calvarial defects were made in the parietal bones of each animal. Group 1 had demineralized bone matrix (DBM) gel placed in one defect, while the other defect was left unfilled and served as the control. Group 2 had one defect filled with calcium hydroxide (CaOH)-treated DBM gel and the other defect filled with DBM gel. Group 3, the calcium-phosphate cement group, had Norian CRS (Norian Corp, Cupertino, CA) placed on one side and Bone Source (Howmedica Leibinger, Dallas, TX) placed on the contralateral side. Five animals in each group were killed at 6 and 12 weeks. Data analysis included qualitative assessment of the calvarial specimens and radiographic evaluation. Histomorphometric analysis was used to quantify the amount of new bone within the defects., Results: Histomorphometric analysis showed that DBM gel-treated defects had significantly more new bone at 12 weeks compared with all other groups. There was no significant difference between defects filled with CaOH-treated DBM gel and those filled with DBM gel at 12 weeks. In group 3, Norian CRS- and Bone Source-treated defects were not statistically different from the unfilled controls., Conclusion: DBM gel was an effective allogeneic bone substitute that showed reliable osseous healing of critical size defects in the rabbit calvarium. The addition of CaOH to DBM gel did not significantly improve the bone regenerative capacity of the DBM gel. Both Norian CRS and Bone Source did not promote bone regeneration in this animal model.

Purpose: This study evaluates bone regeneration of critical sized cranial vault defects in New Zealand white rabbits using four commercially available bone substitutes: OsteoSet (calcium sulphate pellets), DynaGraft Putty (demineralized bone matrix delivered in a poloxmer excipient), Norian CRS, and Bone Source (two commercially available calcium phosphate cements)., Materials and Methods: Critical sized defects 15 mm in diameter were created bilaterally in the parietal bones of 30 adult male New Zealand White rabbits. They were divided into three groups with ten animals in each. Bone healing was assessed clinically, radiographically, and histomorphometrically. Group 1 had calcium sulfate bioimplant on one side of the calvarium and an unfilled defect on the contralateral side. Group 2 had DBM putty on one side and Poloxamer gel on the contralateral side. Group 3, the Calcium phosphate cements (CPC), had Norian CRS on one side and Bone Source on the contralateral side. Five animals in each group were killed at 6 weeks and 12 weeks post operatively., Results: All unfilled defects healed with fibrous scar, as did the Plaster of Paris and the poloxamer gel defects. Defects reconstructed with the demineralized bone matrix putty healed with bone throughout the entire defect. This was obvious clinically and radiographically where the defects appeared completely filled with a dense radiopaque tissue. The six-week group displayed new bone formation (87.1%) surrounding the remaining allogeneic particles. Resorption was evidenced by the presence of osteoclastic activity and by the significant decrease in the size of the demineralized bone particles. By 12 weeks, the demineralized bone putty bioimplant was almost completely replaced by new bone (95.5%). Both calcium phosphate cement groups (Norian CRS and Bone Source) had identical patterns of healing. They clinically were visible and firm and uniformly radiopaque with little evidence of new bone formation. Histologically the cement remained unresorbed with little new bone with in the defect at 12 weeks., Conclusions: The utilization of a demineralized bone matrix putty appeared to allow for complete closure of critical sized calvarial defects in New Zealand white rabbits with viable new bone at 12 weeks.