Serum levels of BMP-2, 4, 7 and AHSG in patients with degenerative joint disease requiring total arthroplasty of the hip and temporomandibular joints.

To date, there is no objective or reliable means of assessing the severity of degenerative joint disease (DJD) and need for joint replacement surgery. Hence, it is difficult to know when an individual with DJD has reached a point where total arthroplasty is indicated. The purpose of the present study is to determine whether serum levels of Alpha-2 HS-glycoprotein (AHSG) as well as bone morphogenetic proteins (BMP-2, 4, 7) can be used to predict the presence of severe DJD of the hip and/or temporomandibular joint (TMJ) (specifically: joints that require replacement). A total of 30 patients scheduled for arthroplasty (diseased) (15 HIP, 15 TMJ) and 120 age-matched controls (healthy/non-diseased) were included. Blood samples were collected from all patients ≥8 weeks after the last arthroplasty. Concentrations of serum analytes were measured using enzyme-linked immunosorbent assays, and these were compared between the Diseased and Healthy groups, utilizing the Mann-Whitney U-test. Patients with disease had significantly higher levels of BMP-2 and BMP-4 and lower levels of AHSG in serum compared to non-diseased humans (p < 0.01). Higher levels of BMP-2, 4 and reduced levels of AHSG appear to characterize patients who have DJD that is severe enough to require total joint replacement. Perhaps measurements of these proteins can be used to make objective decisions regarding the need for total arthroplasty as opposed to the current subjective approaches.

Mutation of a cleavage site adjacent to the mature domain leads to increase in secreted mature BMP-2 with reduced activity.

Proteolytic cleavage of precursor bone morphogenetic protein (proBMP) is an important step in generating the active mature BMP. ProBMP-2 contains two proprotein convertase (PC) recognition sites (S1 and S2) and is postulated to be cleaved by PCs at those sites. Cell lines expressing proBMP-2, with a silenced S1 site (mS1) that inhibited PC cleavage, secreted the 20-kDa form BMP-2, while cells expressing wild type (wt) BMP-2 secreted 18- and 20-kDa mature BMP-2 N-terminal isoforms. The mS1 cells secreted 15-fold more mature BMP-2 than the wt, despite their similar mRNA levels. Mutant-secreted BMP-2 demonstrated biological activity in vitro; however, its activity was reduced compared with wt. These data demonstrate that proBMP-2 can be cleaved at an alternative cleavage site without prior S1 site cleavage in cell lines overexpressing BMP-2 and more importantly suggest that the presence of the 2-kDa linker peptide can affect activity and secretion of the mature protein.

Polyarginine peptide IND-1 enhances recombinant human bone morphogenetic protein-2 yield in mammalian cells.

To improve recombinant human bone morphogenetic protein-2 (rhBMP-2) yield, cell lines stably expressing hBMP2 were cultured in the presence of polyarginine peptide IND-1 and showed up to 6-fold increase in the yield of mature BMP-2. Repeated addition of IND-1 to cell cultures consistently improved BMP-2 yields over 53 days without affecting cell growth and viability. Investigation of its mechanism of action showed that IND-1 inhibited pro-protein convertase (PC) activity when incubated with cell lysates. However, when intact cells were cultured with IND-1, no change in cellular PC activity was observed. Furthermore, knockdown of furin (a prototypical member of the PCs) in cells did not affect their BMP-2 yields, suggesting furin/PC inhibition is unlikely the mechanism by which IND-1 enhances BMP-2 yields. IND-1 as a medium additive thus enhances BMP-2 production in mammalian cell expression systems.

Osteoinductivity of partially purified bovine, ostrich and emu bone morphogenetic proteins in vitro.

The aim of this study was to observe the osteogenic activity of native bone morphogenetic proteins (BMPs) obtained from different species including bovine, ostrich and emu sources in order to compare mammalian and avian BMPs. Rat mesenchymal progenitor marrow stromal cells and pre-osteoblastic C2C12 cell cultures, were exposed to the native BMPs and alkaline phosphatase (ALP) and creatine kinase (CK) levels were determined by assay. The results showed that the ALP activity in C2C12 cultures was elevated by bovine BMP by 2- to 10-fold (p < 0.05-0.001) from day 3 during 14 days. There were no significant differences in avian BMP related elevations of ALP activity except with ostrich BMPs at day 14 (p < 0.05). However, exposure of MSCs cultures to BMPs derived from bovine, ostrich or emu sources resulted in elevated ALP from day 3 (p < 0.05). Bovine BMP resulted in more ALP elevation than with either of the avian BMPs. All of BMPs elevated Creatine kinase (CK) activity from day 1 and climbed until peaking at day 7. Compared with control cultures, CK was elevated more with exposure to emu BMP and was more elevated with greater statistical significance than with bovine and ostrich BMP before day 5. These higher levels remained until day 14 (p < 0.05). The results of this study suggest that both bovine and avian BMPs are able to stimulate osteogenesis in mature osteoblasts in vitro. The strongest synergistic effect on osteogenesis was detected in cells stimulated with bovine BMP. Avian BMPs had lower effects on ALP and CK activity, emu BMP being more effective than ostrich BMP.

Bisphosphonate-associated osteonecrosis of the jaw in Ontario: a survey of oral and maxillofacial surgeons.

OBJECTIVE: Osteonecrosis of the jaw (ONJ) in association with use of bisphosphonate (BP) has been described primarily in cancer patients receiving high-dose intravenous BP. The frequency of the condition in patients with osteoporosis appears to be low. We evaluated the frequency of BP-associated ONJ in Ontario in the cancer population and in those receiving BP for osteoporosis and metabolic bone disease. METHODS: A survey developed by representatives of the Ontario Society of Oral and Maxillofacial Surgeons was mailed to Ontario oral and maxillofacial surgeons (OMFS) in December 2006, asking oral surgeons to provide information on cases of ONJ seen in the previous 3 calendar years (2004 to 2006). OMFS were subsequently contacted by telephone if they had not responded or if they had reported cases of ONJ. The frequency of ONJ in association with BP use was estimated from the number of patients with filled prescriptions for BP in Ontario between 2004 and 2006. The cumulative incidence of ONJ was calculated separately for patients using intravenous (IV) BP for cancer treatment and for patients using oral or IV BP for osteoporosis or other metabolic bone disease. RESULTS: Between 2004 and 2006, 32 ONJ cases were identified. Nineteen patients received IV BP for cancer treatment and 13 patients received oral or IV BP for osteoporosis or metabolic bone disease. Over a 3-year period the cumulative incidence of BP-associated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or other metabolic bone disease observations (1.04 per 100,000). The relative risk of low dose IV/oral BP-associated ONJ was 0.002 (95% CI 0.001, 0.005) compared to high-dose IV BP. Other risk factors for ONJ were present in all cases in whom detailed assessment was available. The median duration of exposure to BP was 42 months (range 36 to 120 mo) and 42 months (range 11 to 79 mo) in osteoporosis patients and cancer patients, respectively. CONCLUSION: Over a 3-year period, the cumulative incidence for BP-associated ONJ was 0.442% of cancer patient observations (442 per 100,000) and 0.001% of osteoporosis or metabolic bone disease observations (1.04 per 100,000). This study provides an approximate frequency of BP-associated ONJ in Canada. These data need to be quantified prospectively with accurate assessment of coexisting risk factors.

Augmentation of the maxillary sinus: comparison of bioimplants containing bone morphogenetic protein and autogenous bone in a rabbit model.

OBJECTIVE: To evaluate the effectiveness of various bioimplants used for augmentation of the maxillary sinus floor by means of a rabbit model. MATERIALS AND METHODS: Bone was harvested from the posterior iliac crest of 40 adult New Zealand white rabbits to allow bilateral augmentation of the floor of the maxillary sinus with autogenous bone or other materials. One of the following was grafted to the maxillary sinus of each rabbit: particulated autogenous bone, demineralized bone matrix (DBM), DBM combined with purified bone morphogenetic protein (BMP-DBM bioimplants) and bioimplants consisting of a poloxamer gel with BMP in 1 of 2 different doses. Animals were sacrificed at 2 or 8 weeks. Histologic examination was used to assess biologic healing in the various samples. Histomorphometry was used to demonstrate and quantify bone formation. RESULTS: After 2 weeks, the BMP-containing bioimplants had produced more new bone than any of the other materials. Particulated autogenous bone grafts produced less new bone initially (after 2 weeks), but the amount of bone produced by these grafts gradually increased, to levels comparable to the BMP-containing bioimplants by 8 weeks. For groups in which the poloxamer gel was used as a carrier for BMP or where BMP was used in combination with DBM, the amount of bone generated by 8 weeks was similar to that produced by autogenous bone. CONCLUSION: The rabbit maxillary sinus model allowed evaluation of multiple types of bioimplants that could be suitable for peri-implant maxillary reconstruction. BMP-containing bioimplants demonstrated promise as alternatives to autogenous bone grafts for sinus-augmentation procedures. These bioimplants had more rapid initial bone production than all other materials, including autogenous bone. In the future, such biomaterials may enable earlier placement of dental implants into augmented maxillary sinuses.

The expression of bone matrix proteins induced by different bioimplants in a rabbit sinus lift model.

This study aimed to analyze the expression of bone matrix proteins and CD31 by immunohistochemistry after maxillary sinus grafting with different bioimplants in a rabbit model. Rabbit demineralized bone matrix (DBM), partially purified bovine bone morphogenetic proteins (BMP), a mixture of BMP with DBM (BMP/DBM), or particulated autogenous bone was grafted into the maxillary sinuses of 42 rabbits. Animals were sacrificed at 2 and 8 weeks. Immunohistochemistry was used to investigate the expression of type 1 collagen (COL1), osteonectin (ON), osteocalcin (OC), bone sialoprotein (BSP), osteopontin (OPN), and CD31. Sinuses grafted with BMP were filled with trabeculae of woven bone that was strongly immunoreactive for COL1, OC, ON, and BSP. BMP/DBM showed strongly positive immunoreactivity for these proteins within the newly formed bone, but weak immunoreactivity in the DBM particles. Immunoreactivity for COL1, OC, ON, and BSP in DBM sinuses was only seen in the osteoblasts rimming the grafted bone particles. The staining of autogenous bone graft sinuses was similar to those grafted with DBM. OPN staining was detected in autogenous bone graft, BMP/DBM, and BMP bioimplants. CD31 staining was strongest in BMP and BMP/noncollagenous matrix proteins sinuses. These results suggest that exogenous BMP enhances not only osteogenesis but also angiogenesis, an important part of bone repair.

Calvarial bone wound healing: a comparison between carbide and diamond drills, Er:YAG and Femtosecond lasers with or without BMP-7.

OBJECTIVE: This study compared the healing of 2 laser ablation units, erbium YAG and femtosecond lasers versus conventional mechanical cutting with carbide and diamond drills to explore future applications for bone surgery. The effects of laser or mechanical ablation combined with rhBMP-7 were also investigated. METHODS AND MATERIALS: Following defect standardization, a full-thickness circular defect was created on the parietal bones of 160 mice divided into 4 groups: carbide drill, diamond drill, erbium YAG laser, and femtosecond laser. Each of the 4 ablation groups was treated with and without BMP 7. Hard tissue healing was assessed using microcomputerized tomography at 3 and 12 weeks postsurgical time points. RESULTS: The femtosecond laser created wounds that showed slightly delayed bone healing during the observation period when compared with mechanical drilling, although the difference was not statistically significant. The Er:YAG laser showed a healing rate similar to that of the mechanically ablated groups. When BMP 7 was added to the surgical sites, bone wound closure occurred at a similar rate in all test groups. CONCLUSIONS: The femtosecond and Er:YAG lasers are 2 laser modalities suitable for bone ablation that are comparable to mechanical instrumentation in terms of bone healing. This study suggested that BMP-7 may be used to enhance bone healing with success regardless of the ablative modality used, whether laser or mechanical drilling.

Lemierre syndrome from an odontogenic source: a review for dentists.

Lemierre syndrome, which can result from a recent oropharyngeal or odontogenic infection, is characterized by clinical or radiographic signs of thrombosis of the internal jugular vein, distant infected emboli and the presence of anaerobic pathogens, usually Fusobacterium necrophorum. The septic emboli resulting from the infected thrombophlebitis of the internal jugular vein give the syndrome its constellation of central nervous system, pulmonary and many other manifestations including septic shock. This condition was so rare that, historically, it became known as the "forgotten disease," but an increasing frequency of reports indicates that Lemierre syndrome may not be so uncommon.

Comparison of the osteoinductivity of bioimplants containing recombinant human bone morphogenetic proteins 2 (Infuse) and 7 (OP-1).

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.

Bone healing with an in situ-formed bioresorbable polyethylene glycol hydrogel membrane in rabbit calvarial defects.

OBJECTIVES: The aims of this study were to test whether or not the application of an in situ-formed synthetic polyethylene glycol hydrogel (PEG) used as a biodegradable membrane for guided bone regeneration with a variety of graft materials and ambient oxygen or hyperbaric oxygen (HBO) environments would result in enhanced bone regeneration, and to observe the histologic and histomorphometric aspects of bone healing of the calvarial defects with and without a PEG membrane. STUDY DESIGN: Thirty adult, skeletally mature, male New Zealand white rabbits were randomly divided into 3 groups of 10 animals each. Bilateral 15-mm-diameter critical-size defects were created in the parietal bones of each animal. Group 1 served as a control with unfilled bilateral calvarial defects, group 2 had bilateral calvarial defects filled with morcelized autogenous calvarial bone, and group 3 had bilateral calvarial defects filled with a biphasic calcium phosphate ceramic. One of the calvarial defects was randomly protected with a PEG resorbable liquid membrane in each animal. Five animals from each group underwent a course of HBO treatment (2.4 ATA 100% oxygen for 90 minutes 5 days a week for 4 weeks) and the other 5 served as control and did not receive any supplemental oxygen (normobaric). The animals were killed 6 weeks after their surgery, and their parietal bones were harvested. The specimens were analyzed with microscopic computerized tomography (microCT) scans and histomorphometrics. RESULTS: The unfilled normobaric control bony defects did not heal, proving the critical-size nature of these defects. The presence of autogenous bone or bone ceramic in the defects increased the bone volume fraction and bone mineral density of the defects (P < .001). The presence of a membrane in the ungrafted and autogenous bone grafted defects resulted in a decrease in the corrected bone volume fraction (P = .002) but not in the bone ceramic grafted defects (P = .580). Bony healing of defects where the membrane was unsupported was compromised; the membrane did not maintain the desired bone regeneration volume with the unfilled and autogenous bone grafted groups. The PEG resorbable liquid membrane worked best with the bone ceramic material. HBO did not ameliorate the healing of the autogenous bone graft or ceramic filled defects in the 6-week time period of this study. CONCLUSIONS: Although the PEG resorbable liquid membrane is easy to use and forms an occlusive layer, caution is recommended when using the membrane over an unsupported defect. HBO did not ameliorate bony healing with the membrane at the early 6-week time point. The authors recommend future assessment with HBO at the 12-week time point.

Effect of hyperbaric oxygen on demineralized bone matrix and biphasic calcium phosphate bone substitutes.

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.

Comparison of platelet-rich plasma, bovine BMP, and rhBMP-4 on bone matrix protein expression in vitro.

This study investigated the potential use of platelet-rich plasma (PRP) in conjunction with mRNA expression of bone matrix proteins using bioassay and RT-PCR comparing bovine bone morphogenetic proteins (BMP), recombinant human BMP-4 (rhBMP-4) during rat bone marrow stromal cell (Mesenchymal Stem Cell) differentiation at 14 days. The results showed that all three growth factors were associated with significantly elevated alkaline phosphatase activity. PRP and bovine BMP resulted in increased protein content. The mRNA of type I collagen was expressed with all three growth factors and remained consistently elevated. Osteopontin was observed with PRP from days 1 to 7; bone sialoprotein expression was detected on days 1 and 3. PRP, bovine BMP and rhBMP-4 enhanced the steady-state expression of PDGF-A as time-dependent to day 14 and in PRP was the strongest. PTHr was expressed at days 1 and 5. Vascular endothelial growth factor expression was the most highly expressed after day 3. These findings suggest that PRP increases mRNA expression of bone matrix protein, enchances osteogenesis and angiogenesis in vitro.

Induction of bone matrix protein expression by native bone matrix proteins in C2C12 culture.

OBJECTIVE: To study the expression of bone matrix protein (BMP) induced by bovine bone morphogenetic proteins (BMPs) in vitro. METHODS: Type I collagen, osteopontin (OPN), osteonectin (ON), osteocalcin (OC), and bone sialoprotein (BSP) were detected by immunohistochemistry in C2C12 cultured from day 1 to day 28. RESULTS: The signaling of bone matrix protein expression became weaker except for type I collagen, OC and BSP after 5 days. Fourteen days after culture, the positive signaling of type I collagen, OPN, ON, OC, and BSP was gradually declined, and could be detected significantly as compared with that of the negative control on day 28. BMP assay showed that the alkaline phosphatase (ALP) activity was higher in C2C12 culture than in the control during the 14-day culture. Also, total protein and DNA significantly increased during the 14-day culture. High levels of ALP were seen in preosteoblasts and osteoblasts in vivo and in differentiating osteoblasts in vitro. ALP was well recognized as a marker reflecting osteoblastic activity. CONCLUSION: Native bovine BMP induces conversion of myoblasts into osteoblasts, produces type I collagen, and plays significantly role in osteoinduction and bone matrix mineralization of C2C12 in vitro.

Effect of hyperbaric oxygen on grafted and nongrafted calvarial critical-sized defects.

OBJECTIVES: This study was undertaken to evaluate the effect of hyperbaric oxygen (HBO) on the repair of critical-sized defects in the presence and absence of a nonvascularized autogenous bone graft. STUDY DESIGN: Ten New Zealand White rabbits were randomly divided into 2 groups of 5 animals each. Bilateral 15-mm calvarial defects were created in the parietal bones of each animal, resulting in 20 critical-sized defects. Autogenous bone grafts (ABG) were allocated to the left or right defect of each animal. Group 1 received HBO treatment at 2.4 ATA 100% oxygen for 90 minutes per day 5 days a week for 4 weeks. Group 2 served as a normobaric (NBO) control, breathing only room air. The animals in each group were humanely killed at 6 weeks. Calvaria were analyzed by micro-CT and histomorphometry. RESULTS: Micro-CT analysis indicated that as expected there was a higher bone mineral density (BMD) and bone mineral content (BMC) in ABG than unfilled defects (P < .05). However, there was a significant decline in the bone mineral content (BMC) of HBO-treated grafted defects compared to NBO-treated grafted defects (P < .05). Histologically complete bridging of the defect was observed in both NBO and HBO ABG grafted defects. Histomorphometic analysis showed that HBO treatment increased new bone and marrow, and reduced fibrous tissue in the defects (P < .01 for all). Examination of residual graft showed a near significant reduction in residual graft volume (11.2 +/- 4.7 versus 19.1 +/- 7.7, HBO versus NBO P = .085) in the HBO group. The use of a graft increased new bone and marrow in the NBO group (P < .001 for both); however, in the HBO-treated animals the differences between grafted and ungrafted were not significant. CONCLUSION: HBO enhances bony healing in ungrafted rabbit calvarial critical-sized defects and may increase the rate of residual graft resorption in autogenous bone-grafted defects.

Platelet-rich plasma induces mRNA expression of VEGF and PDGF in rat bone marrow stromal cell differentiation.

OBJECTIVE: To investigate the potentially useful of platelet-rich plasma (PRP) on mRNA expression of angiogenesis. STUDY DESIGN: Adjunct assay and reverse-transcription polymerase chain reaction (RT-PCR) analysis of type I collagen, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) in rat bone marrow stromal cells differentiation in 14 days' culture. RESULTS: The PRP significantly elevated alkaline phosphatase activity after day 5 (P < .05), and DNA and protein content increased at culture days 1, 3, and 5 (P < .01) with PRP compared with control. The RT-PCR demonstrated that type I collagen was expressed in all substrates and remained high with PRP during 14 days of culture, and that mRNA expression of VEGF and PDGF were higher over time. CONCLUSIONS: This study indicates a potential contribution of PRP as possibly starting the process of angiogenesis, recruiting the endothelial cells which line blood vessels, and beginning the initiation of bone regeneration.

Prevention of infective endocarditis: revised guidelines from the American Heart Association and the implications for dentists.

Infective endocarditis is a rare but life-threatening microbial infection of the heart valves or endocardium, most often related to congenital or acquired cardiac defects. The American Heart Association (AHA) recently updated its recommendations on prophylaxis during dental procedures. The revisions will have a profound impact on both the patient and the dental practitioner. The purpose of this paper is to review the pathogenesis and clinical presentation of infective endocarditis and discuss the 2007 AHA guidelines and their implications for dentists.

Reconstruction of 10 major mandibular defects using bioimplants containing BMP-7.

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.

Hyperbaric oxygen results in increased vascular endothelial growth factor (VEGF) protein expression in rabbit calvarial critical-sized defects.

BACKGROUND: Hyperbaric oxygen therapy (HBO) promotes osseous healing, however the mechanism by which this occurs has not been elucidated. HBO may promote angiogenesis, which is vital for bone healing. Vascular endothelial growth factor (VEGF) is one of the key factors that stimulates angiogenesis. OBJECTIVE: The objective of this study was to investigate whether HBO altered VEGF expression during bone healing. METHODS AND MATERIALS: Archived samples from calvarial defects of rabbits exposed to HBO (2.4 ATA, 90 minutes a day, 5 days a week for 4 weeks) and normobaric oxygen controls (NBO) were analyzed by immunohistochemistry. RESULTS: VEGF expression in 6-week HBO samples was elevated compared to NBO (P = .012). Staining of the 12-week HBO samples was reduced compared to 6-week HBO (P = .008) and was similar to 6- and 12-week NBO control samples. CONCLUSION: HBO therapy resulted in increased VEGF expression in the defects even 2 weeks after the termination of treatment (6 weeks postsurgery).

An evaluation of hydroxyapatite and biphasic calcium phosphate in combination with Pluronic F127 and BMP on bone repair.

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.