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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Callus formation in the periosteal bone interface in response to bone morphogenetic protein (BMP) and associated bone matrix noncollagenous proteins (BMP/NCP) was investigated in mature adult rabbits. For controls byproducts of BMP/NCP purification, bone marrow, eight nonskeletal tissues, purified matrix gamma-carboxyglutamic acid-rich protein (MGP), and a composite of BMP/NCP and polylactic-polyglycolic acid polymer (PLA/PGA) were also implanted in the periosteal bone interface. Quantitative microcomputer image analysis and histologic studies were performed three weeks after the implantation. BMP/NCP and bone marrow or BMP/NCP implanted over a single drill hole into the marrow cavity produced three times more new bone than the bone marrow alone. BMP/NCP alone produced twice as much new bone as bone marrow alone. Control implants of bovine serum albumin or purified MGP produced no new bone. Autogeneic minced muscle and ten nonskeletal tissue controls produced little or no bone formation. Even at one-fifth of the dose of BMP/NCP, a composite of PLA/PGA incorporating BMP/NCP showed almost the same amount of new bone as BMP alone. Histologically, the response to BMP/NCP consisted of an external callus of calcifying cartilage and woven bone. The response to subperiosteal implants of BMP/NCP or BMP/NCP with bone marrow or with minced muscle occurred with the same sequence of developmental events as seen either in embryonic skeletogenesis or in fracture callus.
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PMID:Induction of callus formation by implants of bone morphogenetic protein and associated bone matrix noncollagenous proteins. 318 May 78

Twelve patients with intractable nonunions of the femoral diaphyseal or metaphyseal-diaphyseal shaft were successfully treated by a combination of internal fixation and implants of human bone morphogenetic protein (h-BMP). There was an average of 4.3 surgical procedures per patient attempting union prior to h-BMP implantation. Union was obtained in 11 of 12 patients and in one patient with a repeat stabilization and implantation of h-BMP. Four patients received autogeneic cancellous bone graft and four patients received allogeneic bone grafts. The BMP implant was prepared in the form of an aggregate of h-BMP and bone matrix water-insoluble noncollagenous proteins (h-BMP/iNCP). Fifty to 100 mg of h-BMP/iNCP was either implanted in the fracture gap in ultra thin gelatin capsules, or incorporated in a strip of polylactic/polyglycolic acid copolymer (PLA/PGA) and placed as an onlay across the fracture gap. The average time to union was 4.7 months. Further clinical investigations are planned as a series of matched cases with and without BMP augmentation in order to distinguish h-BMP effects from new or improved methods of fracture fixation combined with autogeneic cancellous bone grafts.
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PMID:Bone morphogenetic protein augmentation grafting of resistant femoral nonunions. A preliminary report. 328 78

We developed adequate delivery systems for bone morphogenetic protein (BMP) to express its bone-inducing activity by combining it with biodegradable synthetic polymers, these causing no unfavorable tissue reaction or anti-BMP effect. Their efficacy was tested for ectopic bone formation in mice and reconstruction of large segmental bone defects of the tibiae in rabbits. Composites of semipurified BMP and polylactic acid--polyethylene glycol block copolymer (PLA-PEG), and composites of BMP, PLA-PEG and lactic acid--glycolic acid copolymer (PLGA) were implanted under the fasciae of the dorsal muscles of mice. Three weeks after implantation, both the BMP/PLA-PEG and BMP/PLA-PEG/PLGA composites were completely absorbed and replaced by newly induced bone with hematopoietic marrow. Because the BMP/PLA-PEG composite is a viscous semiliquid and the BMP/PLA-PEG/PLGA composite is a plastic and moldable, the former can be used as an injectable bone-inducing material and the latter as a plastic mold. The BMP/PLA-PEG/PLGA composites were implanted in large segmental bone defects in the tibiae in rabbits. Twelve weeks after implantation, the bone defect was completely restored by a newly formed bone mass of the original thickness and structure.
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PMID:Bone induction and bone repair by composites of bone morphogenetic protein and biodegradable synthetic polymers. 815 40

A new biodegradable polymer, a polylactic acid-polyethylene glycol (PLA-PEG) block copolymer, proved to be an effective and suitable carrier for bone morphogenetic protein (BMP). Composites of semipurified BMP and PLA-PEG consisting of a PLA segment with a molecular weight (MW) of 650 d and a PEG segment with a MW of 200 d (PLA-PEG 650-200) were implanted under the fasciae of the dorsal muscles of mice. Three weeks after implantation, the PLA-PEG 650-200/BMP composites were completely absorbed and replaced by newly induced bone with hematopoietic marrow. The composites induced twice as much bone as composites of BMP and a 650-d PLA homopolymer. Results indicate that of all the biodegradable synthetic polymers the authors have tested, PLA-PEG 650-200 is the most suitable and effective BMP carrier. Composites of PLA-PEG 650-200/BMP and hydroxyapatite powder (HAP) also induced ectopic bone formation. Because PLA-PEG 650-200/BMP is viscous and semiliquid and PLA-PEG 650-200/BMP/HAP is doughy and plastic, the former can be used as an injectable osteoinductive material and the latter as a plastic mold.
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PMID:Polylactic acid-polyethylene glycol block copolymer. A new biodegradable synthetic carrier for bone morphogenetic protein. 835 39

Non-union of long bone fractures is often a serious complication of fracture healing. It is estimated that 100 000 non-unions occur in the united States annually and result in the loss of function of the involved limb. The present study was performed to develop a microporous polylactic acid-polyglycolic acid (PLA-PGA) implant for the delivery of bone morphogenetic protein (BMP) to sites of fracture non-unions, and to characterize the protein release kinetics of such an implant in vitro. A 50:50 copolymer of PLA-PGA was used to fabricate the implants using a gel formation technique. The implants were subjected to hydrolytic degradation in phosphate-buffered saline at 37 degrees C for up to 72 d. The protein release and the polymer degradation were monitored during this time period. The release kinetics of these implants were studied using a model protein, soybean trypsin inhibitor (TI), as well as BMP. The results indicate that there is a burst release of the proteins in the initial 48 h followed by a lower elution rate. The release of both the proteins followed similar trends. The molecular weight of the polymer decreased at a faster rate compared to its mass.
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PMID:Protein release kinetics of a biodegradable implant for fracture non-unions. 858 96

A fundamental understanding of the in vivo biodegradation phenomenon as well as an appreciation of cellular and tissue responses which determine the biocompatibility of biodegradable PLA and PLGA microspheres are important components in the design and development of biodegradable microspheres containing bioactive agents for therapeutic application. This chapter is a critical review of biodegradation, biocompatibility and tissue/material interactions, and selected examples of PLA and PLGA microsphere controlled release systems. Emphasis is placed on polymer and microsphere characteristics which modulate the degradation behaviour and the foreign body reaction to the microspheres. Selected examples presented in the chapter include microspheres incorporating bone morphogenetic protein (BMP) and leuprorelin acetate as well as applications or interactions with the eye, central nervous system, and lymphoid tissue and their relevance to vaccine development. A subsection on nanoparticles and nanospheres is also included. The chapter emphasizes biodegradation and biocompatibility; bioactive agent release characteristics of various systems have not been included except where significant biodegradation and biocompatibility information have been provided.
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PMID:Biodegradation and biocompatibility of PLA and PLGA microspheres. 1083 62

The effects of bone morphogenetic protein (BMP) which can induce bone formation have been surely proved, Porous polylactic-acid blocks were prepared by a freeze-drying method. During preparation of the blocks, recombinant human bone morphogenetic protein-2(rhBMP-2) was mixed with the polylactic-acid(4 mg per block). PLA-rhBMP-2 was implanted in the mandibular defects of rabbit and retrieved after 2 or 4 weeks. The results showed that: with the PLA-rhBMP-2 blocks, new bone formation was observed in 2 weeks after implantation, and plain PLA blocks produced a little of new bone formation in the edges of defect even in 4 weeks after implantation. Calcium content of the retrieved PLA-rhBMP-2 block was statistically higher than that of plain PLA blocks. These results suggest that PLA may be effective delivery system for BMP and the PLA/rhBMP-2 block may potentially have usefulness as a bone graft substitute.
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PMID:[Early observation of healing of rabbit mandibular defects with porous blocks consisting of polylactic acid and recombinant human bone morphogenetic protein-2]. 1147 95

To develop a new technology that enhances the regeneration potential of bone and the repair of large intercalated defects in long bone, recombinant human bone morphogenetic protein-2 (BMP-2; 20 microg or 40 microg) was mixed in a polymer gel (poly-lactic acid-polyethyleneglycol block copolymer; PLA-PEG; 200 mg) and incorporated into titanium fiber-mesh cylinders. Three 5-mm cylinders were placed end-to-end to fill a 15-mm defect created in the humeri of adult rabbits and were stabilized by an intramedullary rod. In controls, the titanium fiber-mesh cylinders were combined with PLA-PEG in the absence of BMP. Six weeks after implantation, new bone had formed on the surface of the implant and had bridged the defect. All of the defects (5/5) treated by cylinders containing 120 microg (40 microg x 3) of BMP were repaired completely. New bone formation was also found inside the pores of the cylinders. The defect was not repaired in the control animals. These results demonstrate that these new composite implants fabricated by combining rhBMP, synthetic degradable polymers and compatible biomaterials enhance the regeneration potential of bone. Thus, it is possible that large skeletal defects can be repaired using this prosthesis in lieu of autogenous bone graft.
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PMID:Repair of segmental defects in rabbit humeri with titanium fiber mesh cylinders containing recombinant human bone morphogenetic protein-2 (rhBMP-2) and a synthetic polymer. 1220 36

The purpose of this study was to achieve spinal fusion in the absence of bone graft material using a new, injectable, and semi-liquid synthetic polymer (polylactic acid polyethylene glycol [PLA-PEG] block copolymer) containing recombinant human bone morphogenetic protein-2 (rhBMP-2). Twenty-seven skeletally mature beagles underwent anterior thoracic spinal fusion at T9-T10. Group I (n = 9) was injected with 1 mL of PLA-PEG block copolymer carrier alone into space under the vertebral pleura and the anterior longitudinal ligament. Group II (n = 9) was injected with 1 mL of PLA-PEG carrier containing 500 microgram of rhBMP-2. Group III (n = 9) was injected with 1 mL of PLA-PEG carrier containing 1000 microgram of rhBMP-2. In the Group I animals, no evidence of new bone formation was noted at the implanted sites both radiographically and histologically. In contrast, all of the nine animals in Group III showed new bone formation in 12 weeks, and four of the nine animals in Group II showed bony mass at the injected sites. However, vertebral bony fusion was incomplete despite the significant amount of new bone formation in both groups that showed new bone formation. In addition to resulting in improvements in the surgical procedure, injection of rhBMP-2 and a synthetic polymer is useful for bone formation for spinal fusion.
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PMID:Anterior thoracic spinal fusion in dogs by injection of recombinant human bone morphogenetic protein-2 and a synthetic polymer. 1267 67

Total hip arthroplasty (THA) has become an almost standard procedure for the treatment of various hip lesions. However, one of the limitations has been the mechanical loosening of the prosthesis, a condition termed peri-prosthetic osteolysis. Consequently, at revision surgery, various grades of bone defect are often noted. Alternative approaches aimed at overcoming this problem have included a special design of the revision prosthesis and allo- or autogeneic bone grafting in combination with or without biomaterials. In a further attempt to address the loosening of the prosthesis, we have combined human bone morphogenetic protein-2, produced by DNA recombination (rhBMP-2) with a new synthetic biodegradable polymer (poly-D,L-lactic-acid-para-dioxanone-polyethyleneglycol block co-polymer; PLA-DX-PEG). We present data on the efficacy of the rhBMP-2 laden prosthesis to reconstruct a bone defect in a canine model. In this model, medial half of the proximal femur was surgically resected to create a bone defect that was repaired with the rhBMP-2/PLA-DX-PEG composite. Twelve weeks after implantation, the original bone defects in the rhBMP-2 treatment groups had been repaired. Thus, this type of 'hybrid' prosthesis may provide a new modality to repair bone defects or restore lost bone mass encountered in revision arthroplasty.
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PMID:Repair of a proximal femoral bone defect in dogs using a porous surfaced prosthesis in combination with recombinant BMP-2 and a synthetic polymer carrier. 1269 51


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