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

A new method to prepare PLA/CMP (poly-L-lactide/calcium metaphosphate) composite scaffolds was developed for effective bone tissue engineering. This novel sintering method is composed of pressing the mixture of PLA, CMP, and salt particles at 150 MPa for 3 min followed by heat treatment at 210 degrees C for 30 min. The scaffolds had a homogeneously interconnected porous structure without a skin layer, and they exhibited a narrower pore size distribution and higher mechanical strength in comparison with scaffolds made by a solvent casting method. The scaffolds were seeded by osteoblasts and cultured in vitro or implanted into nude mice subcutaneously for up to 5 weeks. The number of cells attached to and proliferated on the scaffolds at both in vitro and in vivo was in the order of; PLA by novel sintering < PLA/CMP by solvent casting < PLA/CMP by novel sintering. In addition, the alkaline phosphatase activity of and calcium deposition in the scaffolds explanted from mice were enhanced significantly for the scaffolds by novel sintering compared to them by solvent casting. The in vitro results agreed well with the in vivo data. Such a superior characteristic of the novel sintering method should have resulted from the fact that the CMP particles could contact directly with cells/tissues to stimulate the cell proliferation and osteogenic differentiation, while the CMP particles would be coated by polymers and hindered to interact with cells/tissues in the case of a solvent casting method. As the novel sintering method does not use any solvents it offers another advantage to avoid problems associated with solvent residue.
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PMID:A poly(lactic acid)/calcium metaphosphate composite for bone tissue engineering. 1591 59

The aim of this investigation was to test the biocompatibility of three-dimensional bioresorbable foams made of poly(L-lactic acid) (PLA), alone or filled with hydroxyapatite (HA) or beta-tricalcium phosphate (beta-TCP), with human primary osteoblasts, using a direct contact method. Porous constructs were processed by supercritical gas foaming, after a melt-extrusion of ceramic/polymer mixture. Three neat polymer foams, with pore sizes of 170, 310, and 600 microm, and two composite foams, PLA/5 wt% HA and PLA/5 wt% beta-TCP, were examined over a 4-week culture period. The targeted application is the bone tissue-engineering field. For this purpose, human fetal and adult bone cells were chosen because of their highly osteogenic potential. The association of fetal bone cells and composite scaffold should lead to in vitro bone formation. The polymer and composite foams supported adhesion and intense proliferation of seeded cells, as revealed by scanning electron microscopy. Cell differentiation toward osteoblasts was demonstrated by alkaline phosphatase (ALP) enzymatic activity, gamma-carboxylated Gla-osteocalcin production, and the onset of mineralization. The addition of HA or beta-TCP resulted in higher ALP enzymatic activity for fetal bone cells and a stronger production of Gla-osteocalcin for adult bone cells.
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PMID:Biocompatibility of bioresorbable poly(L-lactic acid) composite scaffolds obtained by supercritical gas foaming with human fetal bone cells. 1641 9

To produce an osteogenic and bacteriocidal biomaterial for the treatment of infected nonunions or bone defects, a synthetic degradable block copolymer of poly-D,L-lactic acid segments with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) segments was mixed with recombinant human BMP-2 (rhBMP-2) and antibiotics at high concentration. We then examined the in vitro elution profile of an antibiotic (teicoplanin) from the polymer, the effects of antibiotics on the bone-inducing capacity of rhBMP-2 or on ectopic new bone formation induced by the rhBMP, and the ability of the polymer to repair bone in a rat cranial defect model. Approximately 40% of teicoplanin was released within the first 24 h, with the remaining amount released steadily over 21 days with no loss of antibacterial activity. The polymer had disappeared by degradation in the phosphate buffered saline (pH 7.4) at the end of the incubation period. The in vivo performance of pellets with antibiotics and rhBMP-2 revealed no significant change in bone yield within the ossicles after 3 weeks. Also, antibiotics had no inhibitory effect on the ability of rhBMP2 to repair cranial defects. Indeed, when the defect was filled by a polymer disc loaded with rhBMP-2 with or without teicoplanin, the defect was repaired by new bone, and normal anatomy was restored within 6 weeks. In conclusion, the PLA/DX/PEG polymer appears to work as effectively for antibiotics as it does for rhBMP-2. Additionally, the biological activity of rhBMP-2 was retained irrespective of the presence of antibiotics.
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PMID:A biodegradable delivery system for antibiotics and recombinant human bone morphogenetic protein-2: A potential treatment for infected bone defects. 1647 65

Despite the widespread role of transforming growth factor-beta3 (TGFbeta3) in wound healing and tissue regeneration, its long-term controlled release has not been demonstrated. Here, we report microencapsulation of TGFbeta3 in poly-d-l-lactic-co-glycolic acid (PLGA) microspheres and determine its bioactivity. The release profiles of PLGA-encapsulated TGFbeta3 with 50:50 and 75:25 PLA:PGA ratios differed throughout the experimental period. To compare sterilization modalities of microspheres, bFGF was encapsulated in 50:50 PLGA microspheres and subjected to ethylene oxide (EO) gas, radio-frequency glow discharge (RFGD), or ultraviolet (UV) light. The release of bFGF was significantly attenuated by UV light, but not significantly altered by either EO or RFGD. To verify its bioactivity, TGFbeta3 (1.35 ng/mL) was control-released to the culture of human mesenchymal stem cells (hMSC) under induced osteogenic differentiation. Alkaline phosphatase staining intensity was markedly reduced 1 week after exposing hMSC-derived osteogenic cells to TGFbeta3. This was confirmed by lower alkaline phosphatase activity (2.25 +/- 0.57 mU/mL/ng DNA) than controls (TGFbeta3- free) at 5.8 +/- 0.9 mU/mL/ng DNA (p < 0.05). Control-released TGFbeta3 bioactivity was further confirmed by lack of significant differences in alkaline phosphatase upon direct addition of 1.35 ng/mL TGFbeta3 to cell culture (p > 0.05). These findings provide baseline data for potential uses of microencapsulated TGFbeta3 in wound healing and tissue-engineering applications.
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PMID:Sustained release of TGFbeta3 from PLGA microspheres and its effect on early osteogenic differentiation of human mesenchymal stem cells. 1657 87

Nanofibers have recently gained substantial interest for potential applications in tissue engineering. The objective of this study was to determine whether electrospun nanofibers accommodate the viability, growth, and differentiation of human mesenchymal stem cells (hMSCs) as well as their osteogenic (hMSC-Ob) and chondrogenic (hMSC-Ch) derivatives. Poly(d,l-lactide-co-glycolide) (PLGA) beads with a PLA:PGA ratio of 85:15 were electrospun into non-woven fibers with an average diameter of 760+/-210 nm. The average Young's modulus of electrospun PLGA nanofibers was 42+/-26 kPa, per nanoindentation with atomic force microscopy (AFM). Human MSCs were seeded 1-4 weeks at a density of 2 x 10(6)cells/mL in PLGA nanofiber sheets. After 2 week culture on PLGA nanofiber scaffold, hMSCs remained as precursors upon immunoblotting with hKL12 antibody. SEM taken up to 7 days after cell seeding revealed that hMSCs, hMSC-Ob and hMSC-Ch apparently attached to PLGA nanofibers. The overwhelming majority of hMSCs was viable and proliferating in PLGA nanofiber scaffolds up to the tested 14 days, as assayed live/dead tests, DNA assay and BrdU. In a separate experiment, hMSCs seeded in PLGA nanofiber scaffolds were differentiated into chodrogenic and osteogenic cells. Histological assays revealed that hMSCs continuously differentiated into chondrogenic cells and osteogenic cells after 2 week incubation in PLGA nanofibers. Taken together, these data represent an original investigation of continuous differentiation of hMSCs into chondrogenic and osteogenic cells in PLGA nanofiber scaffold. Consistent with previous work, these findings also suggest that nanofibers may serve as accommodative milieu for not only hMSCs, but also as a 3D carrier vehicle for lineage specific cells.
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PMID:Continuing differentiation of human mesenchymal stem cells and induced chondrogenic and osteogenic lineages in electrospun PLGA nanofiber scaffold. 1701 Apr 25

Fetal bone cells were shown to have an interesting potential for therapeutic use in bone tissue engineering due to their rapid growth rate and their ability to differentiate into mature osteoblasts in vitro. We describe hereafter their capability to promote bone repair in vivo when combined with porous scaffolds based on poly(l-lactic acid) (PLA) obtained by supercritical gas foaming and reinforced with 5 wt.% beta-tricalcium phosphate (TCP). Bone regeneration was assessed by radiography and histology after implantation of PLA/TCP scaffolds alone, seeded with primary fetal bone cells, or coated with demineralized bone matrix. Craniotomy critical size defects and drill defects in the femoral condyle in rats were employed. In the cranial defects, polymer degradation and cortical bone regeneration were studied up to 12 months postoperatively. Complete bone ingrowth was observed after implantation of PLA/TCP constructs seeded with human fetal bone cells. Further tests were conducted in the trabecular neighborhood of femoral condyles, where scaffolds seeded with fetal bone cells also promoted bone repair. We present here a promising approach for bone tissue engineering using human primary fetal bone cells in combination with porous PLA/TCP structures. Fetal bone cells could be selected regarding osteogenic and immune-related properties, along with their rapid growth, ease of cell banking and associated safety.
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PMID:Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering. 1817 42

Due to an increasing aging population the need for innovative approaches to aid skeletal repair and reconstruction is a significant socio-economic increasing problem. The emerging discipline of tissue engineering has sort to augment the growth and repair of bone loss particularly in areas of trauma, degeneration and revision surgery. However, the initiation and development of a fully functional vascular network are critical for bioengineered bone to repair large osseous defects, whether the material is osteosynthetic (poly (d,l)-lactic acid, PLA) or natural bone allograft. Quantification and three-dimensional visualization of new vessel networks remain a problem in bone tissue engineering constructs. A novel technique utilising a radio-opaque dye and micro-computed tomography (muCT) has been developed and applied to study angiogenesis in an impaction bone graft model. Tissue-engineered constructs combining human bone marrow stromal cells (HBMSC) with natural allograft and synthetic grafts (PLA) were impacted and implanted into the subcutis of MF-1 nu/nu mice for a period of 28 days. Microfil consisting of radio-opaque polymer was perfused through the mice and scanned using a Bench Top CT system for micro-computed tomography. Analysis of three-dimensional muCT reconstructions demonstrated an increase in vessel volume and vessel number in the impacted scaffolds/HBMC compared to scaffolds alone. Vessel volume: allograft/HBMSC=0.57 mm(3)+/-0.19; allograft=0.04 mm(3)+/-0.04; PLA/HBMSC=1.19 mm(3)+/-0.31; and PLA=0.12 mm(3)+/-0.01. Penetrating vessel number: allograft/HBMSC=22.33+/-3.21; allograft=3.67+/-1.153; PLA/HBMSC=32.67+/-8.33; and PLA=7.67+/-3.06. Type 1 collagen and von Willebrand factor immunohistochemistry in scaffold/HBMSC constructs indicated the osteogenic cell phenotype, and new blood vessel formation respectively. Contrast-enhanced 3D reconstructions facilitated the visualization and quantification of neovascularisation. This novel technique has been used to demonstrate neovascularisation in impacted tissue engineered constructs providing a facile approach with wide experimental application.
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PMID:Development of in vivo muCT evaluation of neovascularisation in tissue engineered bone constructs. 1842 49

Concerns over disease transmission, high costs and limited supply have led to interest in synthetic grafts in the field of impaction bone grafting (IBG). Poly(DL-lactic acid) (PLA) grafts are attractive alternatives due to their biocompatibility, established safety and versatile manufacturing process. This study examined the potential of PLA scaffolds augmented with human bone marrow stromal cells (HBMSCs) in IBG. In vitro and in vivo studies were performed on impacted morsellised PLA seeded with HBMSC and compared to PLA alone. In vitro samples were incubated under osteogenic conditions and in vivo samples were implanted subcutaneously into severely compromised immunodeficient mice, for 4 weeks. Biochemical, histological, mechanical and 3D micro-computed tomography analyses were performed. HBMSC viability, biochemical activity and histological evidence of osteogenic cellular differentiation, post-impaction were observed in vitro and in vivo in PLA/HBMSC samples compared to impacted PLA alone. In vitro PLA/HBMSC samples demonstrated evidence of mechanical enhancement over PLA alone. In vivo studies showed a significant increase in new bone and blood vessel formation in the PLA/HBMSC constructs compared to PLA alone. With alternatives to allograft being sought, these studies have demonstrated PLA/HBMSC living composites, to be a potential prospect as a biological bone graft extender for future use in the field of IBG.
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PMID:The application of human bone marrow stromal cells and poly(dl-lactic acid) as a biological bone graft extender in impaction bone grafting. 1845 20

We investigated the in vivo osteogenic ability of rhBMP-2 induced periosteal cells in a new porous scaffold, nano-hydroxyapatite (nano-HA)/collagen/poly(L-lactic acid) (PLA). The nano-HA/collagen/PLA composites were utilized as an extracellular matrix for a cell-based strategy of bone tissue engineering. Periosteal cells were cultivated with 500 ng ml(-1) rhBMP-2, followed by seeding into prewet nano-HA/collagen/PLA scaffolds. The cell-scaffold constructs were then subcutaneously implanted in nude mice compared to controls with cell suspension and scaffold alone. Scanning electron microscopy examination proved that the scaffold supported adhesion and proliferation of periosteal cells. Histological bone formation was observed only in experimental groups with cell transplants 8 weeks post-implantation. The animals of the control groups did not show bone formation. The results strongly encourage the approach of the transplantation of rhBMP-2 induced periosteal cells within a suitable carrier structure for bone regeneration.
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PMID:A study on a tissue-engineered bone using rhBMP-2 induced periosteal cells with a porous nano-hydroxyapatite/collagen/poly(L-lactic acid) scaffold. 1846 Jul 57

As a new member of polyhydroxyalkanoate (PHA) family, the novel polyester poly(3-hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyhexanoate) (P(3HB-4HB-3HHx)) was produced by recombinant Aeromonas hydrophila 4AK4 and used for the first time to test its biocompatibility. It was shown that P(3HB-4HB-3HHx) had higher hydrophobicity, surface energy, and rougher surface than the well-studied polymers poly(L-lactic acid) (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx). Human mesenchymal stem cells (MSCs) attached better on P(3HB-4HB-3HHx) film than on tissue culture plates (TCPs), PLA film, and PHBHHx film. MSC proliferation on P(3HB-4HB-3HHx) film was 126% higher than that on TCPs, 84% higher than that on PHBHHx film, and 312% higher than that on PLA film (p < 0.01). P(3HB-4HB-3HHx) also supported osteogenic differentiation of MSCs. Previous studies found that all PHA materials tested were either less than or equal to TCPs for supporting cell growth. Among all PHA materials tested, P(3HB-4HB-3HHx) was the only PHA material to significantly promote cell proliferation compared with TCPs. P(3HB-4HB-3HHx) could be exploited for applications in bone tissue engineering.
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PMID:Influence of poly(3-hydroxybutyrate-co-4-hydroxybutyrate-co-3-hydroxyhexanoate) on growth and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. 1864 27


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