BACKGROUND: To determine if exogenously injected bone marrow derived platelet-rich plasma (PRP) plus bone morphogenetic protein (BMP)-2 could accelerate the healing of bone-tendon junction injuries and increase the junction holding strength during the early regeneration period. METHODS: A direct injury model of the bone-tendon junction was made using an Achilles tendon-calcaneus bone junction in a rabbit. In the PRP/BMP-2/fibrin group, 0.05 mL of bone marrow derived PRP and 100 ng/mL of BMP-2 both incorporated into 0.1 mL of fibrin glue were injected into Achilles tendon-calcaneus bone junctions. The effect of the intervention was tested by comparing the results of an intervention group to a control group. The results of biomechanical testing, and histological and gross analyses were compared between the 2 groups at the following time points after surgery: 2 weeks, 4 weeks, and 8 weeks. RESULTS: Histologic examinations showed that woven bone developed in tendon-bone junctions at 2 weeks after surgery in the PRP/BMP-2/fibrin group. Mechanical test results showed no significant difference between the PRP/BMP-2/fibrin and control groups at 2 and 4 weeks after surgery, but the mean maximal load in the PRP/BMP-2/fibrin group was significantly higher than in the control group (p < 0.05) at 8 weeks after surgery. CONCLUSIONS: Bone marrow derived PRP and BMP-2 in fibrin glue accelerated healing in a rabbit model of tendon-bone junction injury.
Achilles Tendon/*injuries ; Animals ; Bone Marrow ; Bone Morphogenetic Protein 2/*therapeutic use ; Calcaneus/*injuries ; Male ; *Platelet-Rich Plasma ; Rabbits

OBJECTIVETo explore methods for one-stage repairing of nose deformity and alveolar cleft, as well as primary unilateral complete cleft lip.

METHODSThe nose deformity and alveolar cleft were repaired by Carstens' surgical methods, rhBMP-2 was used for correction of alveolar cleft.

RESULTSFrom 2004 to 2008, 45 cases of cleft lip were treated in the United States and followed up for 3-5 years. In 2007, 10 cases of cleft lip were treated in China and followed up for 1 year. All results were satisfactory.

CONCLUSIONSCarstens' surgical methods can be applied for early correction of nose deformity and alveolar cleft in patients with complete cleft lip.

Alveolar Process ; abnormalities ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; therapeutic use ; Cleft Lip ; surgery ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Nose ; abnormalities ; Recombinant Proteins ; therapeutic use ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps ; Transforming Growth Factor beta ; therapeutic use

OBJECTIVETo study the effects of artificial bone composite of bicoral, rhBMP-2 and PLA in repairing calvarial critical-size defects.

METHODSCalvarial defects in 24 rabbits were surgically made and then half of the defects were repaired with the artificial composite bone. Another half of them were repaired with bicoral/PLA composite and served as controls. Four rabbits in each group were sacrificed at 4, 8, 12 weeks after operation, respectively. The treatment effects were evaluated with scanning electron microscopy and mechanical strength testing.

RESULTSNew bone was observed not only in the periphery, but also inside the artificial bone in both groups, but earlier and more new bone formation was observed in treatment group compared with control group. The mechanical strength test showed that the artificial bone in two groups, which had same mechanical strength before implantation, had significant different mechanical strength after operation. The strength of the artificial composite bone was higher than that of controls and was same with normal rabbit calvarial bone.

CONCLUSIONThe artificial composite bone possess a highly repairing ability, and the healing in bone defects may be accomplished by both osteoinductive and osteoconductive mechanism. The material may be used as a good substitute for bone grafting.

Animals ; Anthozoa ; Biocompatible Materials ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; pharmacology ; therapeutic use ; Bone Regeneration ; drug effects ; Bone Substitutes ; therapeutic use ; Implants, Experimental ; Lactic Acid ; therapeutic use ; Polyesters ; Polymers ; therapeutic use ; Rabbits ; Recombinant Proteins ; pharmacology ; therapeutic use ; Skull ; injuries ; surgery ; Transforming Growth Factor beta

OBJECTIVETo observe the effect of calcitonin on the pathology of fusion in lumbar posterior/facet spinal fusion in rabbit model.

METHODSThirty-two male New Zealand white rabbits were used to establish spinal fusion model. Sixteen rabbits received calcitonin at a dose of 1 IU x kg(-1) x d(-1) were classified as calcitonin group, and the remaining 16 rabbits as control group. Rabbits were killed 1, 2, 4, and 8 weeks after operations. Haematoxylin-eosin staining was applied to observe the pathological process of spinal fusion. Expression of bone morphogenetic protein-2 (BMP2) was detected by immunohistochemistry.

RESULTSBone resorption and fibrovascular stroma formation were the main histological presentation 1 week after surgery. Two and 4 weeks after surgery, more cartilage formed with varying degrees of mineralization, while less trabeculae could be observed in the phase of active bone formation. No remarked margin was seen between cartilage and bone tissues. Eight weeks after surgery, trabeculae distributed widely. The pathological process of spinal fusion in calcitonin group was faster than in control group. Emery scores showed significant differences at different time points (F = 265.44, P < 0.001). Calcitonin and time had a positively synergistic effect on Emery scores, and calcitonin caused significant difference in terms of Emery scores since the second week (F = 22.43, P < 0.001). Expressions of BMP, were significantly different at different time points (F = 1186.54, P < 0.001). Also, calcitonin and time had a synergistic effect on BMP2 expression (F = 13.14, P < 0. 001).

CONCLUSIONSEndochondral ossification exists in the spinal fusion process and may be the main way of ossification. Calcitonin may stimulate the expression of BMP2 and thus accelerate the process of spinal fusion.

Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; biosynthesis ; genetics ; Calcitonin ; therapeutic use ; Lumbar Vertebrae ; surgery ; Male ; Rabbits ; Random Allocation ; Spinal Diseases ; drug therapy ; metabolism ; surgery ; Spinal Fusion ; Transforming Growth Factor beta ; biosynthesis ; genetics

Collagen/bone morphogenetic protein composites were prepared with collagen type I sponge and bone morphogenetic protein-2 (BMP-2). The composites were implanted into Latissimus dorsi muscles pouches of rabbits. Samples were studied with ALP staining, Von Kossa staining, HE staining, toluidine blue staining and CD31 histochemical labeling of microvessel. Bony samples were then used to repair mandibular defect. The effects were evaluated by X-ray, compressive strength, economycin fluorescence labeling, HE staining, toluidine blue staining and bone quantity analysis. Bone formation induced by collagen/BMP composites was found as woven bone between 4 and 6 weeks; cartilaginous osteogenesis was the main type of bone formation; microvessels could be seen in the bony tissues; and the bone defects were healed completely 6 weeks after operation. Bone formation induced by collagen/BMP composites in the muscles can be used as a donor to repair the bone defect.
Animals ; Bone Morphogenetic Protein 2 ; chemistry ; therapeutic use ; Bone Regeneration ; drug effects ; Bone Transplantation ; methods ; Collagen Type I ; chemistry ; therapeutic use ; Female ; Implants, Experimental ; Male ; Mandibular Injuries ; surgery ; Muscle, Skeletal ; surgery ; Rabbits ; Random Allocation

This paper is aimed to investigate the repair of rabbit radial bone defect by the recombinant human bone morphogenetic protein 2/poly-lactideco-glycolic acid microsphere with fibrin sealant (rhBMP-2/PLGA/FS). The radial bone defect models were prepared using New Zealand white rabbits, which were randomly divided into 3 groups, experiment group which were injected with eMP-2/PLGA/FS at bone defect location, control group which were injected with FS at bone defect location, and blank control group without treatment. The ability of repairing bone defect was evaluated with X-ray radiograph. Bone mineral density in the defect regions was analysed using the level of ossification. The osteogenetic ability of repairing bone defect, the degradation of the material, the morphologic change and the bone formation were assessed by HE staining and Masson staining. The result showed that rhBMP-2/PLGA/FS had overwhelming superiority in the osteogenetic ability and quality of bone defect over the control group, and it could promote the repair of bone defect and could especially repair the radial bone defect of rabbit well. It may be a promising and efficient synthetic bone graft.
Animals ; Bone Morphogenetic Protein 2 ; therapeutic use ; Bone Regeneration ; drug effects ; Bone Substitutes ; therapeutic use ; Female ; Fibrin Tissue Adhesive ; therapeutic use ; Lactic Acid ; therapeutic use ; Male ; Microspheres ; Polyglycolic Acid ; therapeutic use ; Rabbits ; Radius Fractures ; therapy ; Recombinant Proteins ; therapeutic use ; Transforming Growth Factor beta ; therapeutic use

OBJECTIVETo observe the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in promoting the tendon-bone healing in rabbits after anterior cruciate ligament reconstruction.

METHODSThirty normal adult New Zealand rabbits were divided into 3 groups for anterior cruciate ligament reconstruction using autologous semitendinosus tendons as the graft material. In the rhBMP-2 group, fibrin glue (FG) containing rhBMP-2 was applied to the interface between the tendon graft and the bone tunnel, while in the FG control group, only FG was applied. The blank control group received no treatment after the surgery. The grafts were collected at 2, 4, 8 weeks after the surgery for gross observation and histological examination of the graft incorporation.

RESULTSIn the FG control group, the tendon-bone interface was filled with granulation tissue 2 weeks after the surgery, and the newly generated tissue growing into the bone tunnel and fibroblasts were observed at 4 weeks. Till week 8, Sharpey's fibers were found in the interface with the formation of indirect insertion. In the rhBMP-2 group, the tendon-bone interface was filled with cartilage tissue at 2 weeks, and the four-layer direct insertion was formed at 4 weeks; till week 8, the interface was mainly composed of the direct insertion.

CONCLUSIONrhBMP-2 can induce direct insertion formation in the tendon-bone interface after early anterior cruciate ligament reconstruction. The direct insertion possesses better biomechanical properties than indirect insertion.

Animals ; Anterior Cruciate Ligament ; surgery ; Anterior Cruciate Ligament Injuries ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins ; therapeutic use ; Bone Regeneration ; drug effects ; Bone and Bones ; physiology ; Humans ; Rabbits ; Recombinant Proteins ; therapeutic use ; Reconstructive Surgical Procedures ; methods ; Tendons ; physiology ; Transforming Growth Factor beta ; therapeutic use ; Wound Healing ; drug effects

BACKGROUNDCalcium phosphate cement (CPC) is a biocompatible and osteoconductive bone substitute, and recombinant human bone morphogenetic protein-2 (rhBMP-2) has strong osteoinductibility, therefore we developed a composite bone substitute with CPC and rhBMP-2 and evaluate its reconstruction effect in rabbit orbital defect.

METHODSThirty-six rabbits were randomly divided into two groups and a 5 mm × 5 mm × 2 mm bone defect in the infraorbital rim was induced by surgery in each orbit (72 orbits in all). The orbital defects were treated with pure CPC or composite of CPC and rhBMP-2. The osteogenesis ability of different bone substitute was evaluated by gross observation, histological examination, histomorphometrical evaluation, compressive load-to-failure testing, and scanning electron microscope (SEM).

RESULTSGross observation showed that both bone substitutes were safe and effective for reconstruction of orbital defect. However, histological examination, histomorphometrical evaluation and SEM showed that CPC/rhBMP-2 group had faster speed in new bone formation and degradation of substitute material than CPC group. Compressive load-to-failure testing showed that CPC/rhBMP-2 group had stronger compressive strength than CPC group at every stage with significant difference (P < 0.05).

CONCLUSIONComposite of CPC/rhBMP-2 is an ideal bioactive material for repairing orbital defect, with good osteoconductibility and osteoinductibility.

Animals ; Bone Cements ; therapeutic use ; Bone Morphogenetic Protein 2 ; therapeutic use ; Bone Substitutes ; therapeutic use ; Calcium Phosphates ; therapeutic use ; Female ; Male ; Microscopy, Electron, Scanning ; Orbit ; pathology ; surgery ; ultrastructure ; Osteogenesis ; Rabbits ; Recombinant Proteins ; therapeutic use ; Reconstructive Surgical Procedures ; methods ; Transforming Growth Factor beta ; therapeutic use

OBJECTIVETo study the effects of BMP-2 gene therapy on vascularization in repairing bone defects.

METHODSThe isolated rabbit mesenchymal stem cells (rBMSC), after being transfected by adenovirus carrying BMP-2 gene (Ad-BMP-2) and seeded on xenogeneic bone scaffolds, were used to repair 1.5 cm-long radius bone defects. Five methods were in use in the experiments: Ad-BMP-2 infected rBMSC plus antigen-free bovine cancellous bone (BCB, Group A), rBMSC-BCB plus reconstructed hBMP-2 (Group B1), Ad-LacZ infected rBMSC-BCB (Group C), rBMSC-BCB (Group D) and only BCB scaffolds (Group E). After 4, 8, and 12 weeks of the operations, capillary vessel ink infusion, vascular endothelial growth factor ( VEGF) immunohistochemical staining and histological examination were conducted.

RESULTSAfter 4 weeks of the operations, usually in Group A one newly formed artery was found in every pore between the trabeculae of the BCB. The density of these intraosseous vessels was high in the periphery and decreasing towards the center of the grafts; by transmission electron microscopy, osteoblasts were always next to vascular endothelial cells and gradually developed into osteocytes with the increase of capillary vessel; VEGF expression were apparently enhanced in mesenchymocytes.

CONCLUSIONSBMP-2 gene therapy, by up-regulating VEGF expression, indirectly induces vascularization of grafts and is of great value to the treatment of bone in union and bone defects.

Animals ; Bone Marrow Cells ; cytology ; Bone Morphogenetic Protein 2 ; genetics ; therapeutic use ; Bone Regeneration ; Bone Substitutes ; Cattle ; Forelimb ; blood supply ; diagnostic imaging ; Genetic Therapy ; Mesenchymal Stromal Cells ; Rabbits ; Radiography ; Tissue Engineering ; Transfection ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVESTo observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH).

METHODSA total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment.

RESULTSAfter 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (P<0.01 and P=0.013, respectively), lower vWF, PAI-1 and CRP levels (P=0.019, P<0.01 and P<0.01, respectively), and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were signifificantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, P<0.05).

CONCLUSIONMQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

Adiponectin ; metabolism ; Adult ; Blood Coagulation Factors ; metabolism ; Bone Density ; drug effects ; Bone Morphogenetic Protein 2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Femur Head Necrosis ; blood ; drug therapy ; physiopathology ; Humans ; Male