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

The aim of these studies was to see if a combination of osteopromotive membranes of expanded polytetrafluoroethylene (e-PTFE; GORE-TEX) and BMP, known to separately promote bone healing, would be stimulatory if combined. Bilateral transosseous 'critical size' defects at the mandibular angles in adult male rats were treated with either (i) various BMP preparations only; ii) lateral and medial coverage with e-PTFE membranes only; iii) a combination of various BMPs and membranes; or iv) left untreated. Two semi-purified bovine BMPs (bBMP), comprising collagen as carrier material, and recombinant human (rh) BMP-2 (1, 2 or 8 micrograms), delivered in either biodegradable beads of polylactide/polyglycolide acid (PLA/PGA) or purified collagen, were tested. After 12 or 24 days, block biopsies were taken for histological analysis. The different materials were well tolerated by the hosts and elicited large amounts of newly formed bone widely spread in the surrounding soft tissue. The combinations of bBMP and membranes did not improve the rate of bone healing compared to membranes only. In contrast, the combination of rhBMP-2 in PLA/PGA with membranes was more efficacious than membrane placement only and resulted in bone bridging at 24 days, with a bone contour resembling the original anatomy. The combination of membrane placement with rhBMP-2 may be of value in the clinic for bone regenerative purposes. The results are also of general importance for choosing carrier materials for delivery of other growth-stimulatory substances in combination with membranes.
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PMID:Bone regeneration by a combination of osteopromotive membranes with different BMP preparations: a review. 908 67

This study was undertaken to investigate whether the choice of carrier/delivery system might be crucial for rhBMP-2 induced osteogenesis beneath osteopromotive membranes. Standardized 5-mm transosseous rat mandibular defects were implanted with recombinant human BMP-2 (rhBMP-2) with or without membrane placement. Two doses of rhBMP-2 (1 microg and 8 microg per defect) were delivered with either collagen sponge or bioabsorbable poly(D,L-lactide-coglycolide) (PLA/PGA) beads plus allogenic blood as carriers. Membrane-covered defects (no BMP) served as controls. Virtually all defects treated with rhBMP-2 without membrane placement already were bridged by new bone after 12 days, independent of rhBMP-2 dose or carrier material, and lateral bone growth was extensive outside the original defect. Membrane placement significantly decreased the stimulatory activity of the BMP, as seen after 12 days, even though osteogenesis was more advanced with rhBMP-2 and membrane compared to membrane alone. After 24 days, defects treated with membrane and rhBMP-2 in the PLA/PGA carrier were totally bridged with regenerated bone, whereas defects covered with membrane without BMP implantation displayed an average bone bridging of only 53%. In an overall analysis of the bone regeneration, the PLA/PGA carrier material was found to be superior to the collagen carrier in the presence of membranes, which was, in turn, more efficient than membrane placement alone (no rhBMP-2). There was much less lateral bone growth when BMP implantation was combined with membrane placement. It was concluded that bone formation beneath osteopromotive membranes may be significantly enhanced by rhBMP-2 and that the delivery system can affect the amount of bone formation obtained. For eventual clinical use, membrane placement has the advantage of keeping the growth-stimulatory implant in place as well as obtaining the desired anatomical contour of the bone formed.
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PMID:Importance of delivery systems for growth-stimulatory factors in combination with osteopromotive membranes. An experimental study using rhBMP-2 in rat mandibular defects. 913 67

The purpose of this study was to investigate whether barrier membranes that were earlier shown to promote bone healing in the craniofacial skeleton are capable of producing bone healing in long bone. defects by themselves or in combination with recombinant human bone morphogenetic protein 2 (rhBMP-2). Segmental defects (10 mm long) in the rabbit radius, known to heal as pseudoarthrosis-like defects, were used as the experimental model. Treatment with expanded polytetrafluoroethylene membranes (GORE-TEX Membrane) (n = 10) resulted in only minor amounts of bone formation within the defect and collapse of the membranes was common. When placement of membranes was combined with implantation of rhBMP-2 in a beaded biodegradable copolymeric PLA/PGA carrier, total bony bridging of the defects was accomplished within 10 weeks (n = 5). Osteopromotive membranes combined with mBMP-2 can therefore bring about complete healing of long bones. The membranes exclude soft tissue from the defect and at the same time keep the growth-stimulatory implant in place and maintain the anatomical contour of the bone. The combination of osteopromotive membranes and rhBMP-2 may be of. value in reconstructive bone surgery.
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PMID:Treatment of segmental defects in long bones using osteopromotive membranes and recombinant human bone morphogenetic protein-2. An experimental study in rabbits. 923 93

Bone morphogenetic proteins (BMPs) are multifunctional cytokines, which induce bone and cartilage formation and exert various other effects on many tissues. Since angiogenesis is involved in the bone formation process, certain members in the BMP family may induce angiogenesis. We examined the in vivo angiogenic activity of BMP family members, i.e., growth/differentiation factor (GDF)-5 and BMP-2. GDF-5 induced angiogenesis in both chick chorioallantoic membrane and rabbit cornea assays. In contrast, BMP-2 did not induce angiogenesis. In order to elucidate the mechanism of angiogenesis, we examined the effects of GDF-5 on cultured bovine aortic endothelial cells (BECs). GDF-5 induced plasminogen activator activity and accelerated the migration of BECs in a chemotactic fashion, which may contribute to the process of angiogenesis in vivo. These results suggest that GDF-5 is one of the molecules which induce angiogenesis in the bone formation process.
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PMID:Growth/differentiation factor-5 induces angiogenesis in vivo. 928 71

The study objective was to determine the mechanical integrity and radiopacity of regenerated bone within critical-sized defects (CSDs) in radii of rabbits using recombinant human bone morphogenetic protein 2 (rhBMP-2) with a porous, biodegradable poly(D,L-lactic acid) (PDLLA) carrier (designated PLA). Twenty millimeter, unilateral radial ostectomies were created in 96 skeletally mature New Zealand white rabbits. The rabbits were randomly assigned to six treatment groups with two euthanasia periods. Treatment groups included unfilled defect (n = 8), segmental autograft (n = 8), PLA + 0 microg rhBMP-2 (n = 8), PLA + 17 microg rhBMP-2 (n = 8), PLA + 35 microg rhBMP-2 (n = 8), and PLA + 70 microg rhBMP-2 (n = 8). The radiopacity was significantly greater for the 35- and 70-microg rhBMP-2 groups at 4 weeks compared to unfilled controls, PLA only, and 17-microg rhBMP-2 groups and equivalent to the autograft. At 8 weeks all groups receiving rhBMP-2 were equivalent to the autograft and significantly greater than unfilled defects and PLA alone. Similarly, the biomechanical analysis indicated significantly greater torque at failure for the 35-microg rhBMP-2 group compared to all other groups at 4 weeks. By 8 weeks all groups receiving rhBMP-2 and autograft had significantly greater torque than unfilled controls and PLA alone. These radiomorphometric and biomechanical results indicate PLA may be a suitable carrier for rhBMP-2 used for skeletal regeneration.
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PMID:Radiomorphometry and biomechanical assessment of recombinant human bone morphogenetic protein 2 and polymer in rabbit radius ostectomy model. 985 95

Bone morphogenetic proteins (BMPs) are biologically active molecules capable of eliciting new bone formation. In combination with biomaterials, these proteins can be used in a clinical setting as bone-graft substitutes to promote bone repair. To find new synthetic absorbable polymers with plastic nature that can be used as BMP-carrier materials, six types of poly-D,L-lactic acid-polyethylene glycol block copolymer (PLA-PEG) with various molecular weights of PLA and PEG were synthesized. These were PLA6, 500-PEG3,000 (P-1), PLA11,500-PEG3,000 (P-2), PLA17,500-PEG3,000 (P-3), PLA6,500-PEG1,000 (P-4), PLA15,000-PEG8,000 (P-5), and PLA8, 500-PEG1,000 (P-6). Fifty milligrams of these polymers was mixed with 0 microg (control) or 5, 10, or 20 microg of recombinant human BMP-2 (rhBMP-2). These pellets were implanted into the dorsal muscle pouches of 144 mice (six pellets consisting of the same polymer and dose of rhBMP-2 for a specific group). Three weeks after surgery, the pellets were harvested and examined by radiographic and histological methods. All P-1 pellets with 10 or 20 microg of rhBMP-2 showed bone formation with hematopoietic marrow and bony trabeculae, as did one third of those with 5 microg of rhBMP-2. The incidence of new bone formation with P-2 pellets or that of P-5 pellets was lower than that of P-1 pellets. No bone was formed in any other type of pellet. These results indicated that the PLA6, 500-PEG3,000 polymer with plastic properties was found to work well as a BMP carrier.
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PMID:New synthetic absorbable polymers as BMP carriers: plastic properties of poly-D,L-lactic acid-polyethylene glycol block copolymers. 1040 Aug 88

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 aim of this study was to examine the potential of immunoselected genetically modified human osteoprogenitors to form bone in vivo on porous PLA scaffolds. Human osteoprogenitors from bone marrow were selected using the antibody STRO-1 utilising a magnetically activated cell separation system. The STRO-1(+) fraction isolated 7% of nucleated marrow cells and increased fibroblastic colony formation by 300% and alkaline phosphatase activity by 190% over unselected marrow cell cultures. To engineer bone tissue, STRO-1(+) culture-expanded cells were transduced with AxCAOBMP-2, an adenovirus carrying the human BMP-2 gene, injected into diffusion chambers containing porous PLA scaffolds, and implanted in vivo. After 11 weeks the presence of bone mineral was observed by X-ray analysis and confirmed for mineral by von Kossa, as well as bone matrix composition by Sirius red staining, birefringence, and type I collagen immunohistochemistry. Bone formation in vivo indicates the potential of using immunoselected progenitor cells and ex vivo gene transfer with biodegradable scaffolds, for the development of protocols for the treatment of a wide variety of musculo-skeletal disorders.
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PMID:Immunoselection and adenoviral genetic modulation of human osteoprogenitors: in vivo bone formation on PLA scaffold. 1243 71

The regenerating potential of human bone is limited. The repair of large bone defects often associated with bone tumor resections is not observed, and nonunion or delayed union of bone is a serious problem for fracture treatment. In these cases, autogeneic or allogeneic bone grafting has been routinely indicated, but these approaches require invasive surgical procedures. An alternative approach described in this paper involves the injection of bone morphogenetic proteins (BMPs) in a polymeric delivery system. We demonstrate that synthetic biodegradable polymers, poly-D,L-lactic acid-polyethylene glycol (PLA-PEG) block copolymers, which exhibit an exquisite temperature-dependent liquid-semisolid transition, work well as an injectable delivery system for recombinant human (rh) BMP-2. The thermosensitive property of the PLA-PEG/rhBMP-2 composite is permissive to percutaneous injection when heated. The fluidity of this composite decreases as it cools down to body temperature and the resultant semisolid form provides a scaffold for bone formation through the gradual local release of the rhBMP-2. This new type of injectable osteoinductive material will enable a less invasive approach to surgeries involving the restoration or repair of bone tissues.
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PMID:Local bone formation by injection of recombinant human bone morphogenetic protein-2 contained in polymer carriers. 1268 81

Chitosan has a variety of biological activities. However, little is known about how chitosan modulates the hard tissue forming cells. When we cultured an osteoblastic cell line in alpha-MEM supplemented with 10% FBS and 0.005% chitooligosaccharide for 3 days, alkaline phosphatase (ALP) activity was significantly high compared with the control culture group (p<0.05). This study was focused on gene expression in osteoblasts cultured with water-soluble chitooligosaccharide. cDNA probes were synthesized from isolated RNA and labeled with fluorescent dye. They were hybridized with Human 1.0((R)) cDNA microarray, and fluorescent signal was analyzed. cDNA microarray analysis revealed that 16 genes were expressed at >/=1.5-fold higher signal ratio levels in the experimental group compared with the control group after 3 days. RT-PCR analysis showed that chitosan oligomer induced an increase in the expression of two genes, CD56 antigen and tissue-type plasminogen activator. Furthermore, the expression of mRNAs for BMP-2 was almost identical in the experimental and control groups after 3 days of culture, but slightly increased after 7 days of culture with chitosan oligomer. These results suggest that a super-low concentration of chitooligosaccharide could modulate the activity of osteoblastic cells through mRNA levels and that the genes concerning cell proliferation and differentiation can be controlled by water-soluble chitosan.
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PMID:Early gene expression analyzed by cDNA microarray and RT-PCR in osteoblasts cultured with water-soluble and low molecular chitooligosaccharide. 1473 37


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