Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the study, poly(gamma-glutamic acid) (gamma-PGA) and poly(lactide) (PLA) were used to synthesize block copolymers via a simple coupling reaction between gamma-PGA and PLA to prepare self-assembled nanoparticles. For the potential of targeting liver cancer cells, galactosamine was further conjugated on the prepared nanoparticles as a targeting moiety. gamma-PGA, a water-soluble, biodegradable, and non-toxic compound, was produced by microbial fermentation (Bacillus licheniformis, ATCC 9945a) and then was hydrolyzed. The hydrolyzed gamma-PGA with a molecular weight of 4 kDa and a polydispersity of 1.3 was used, together with PLA (10 kDa, polydispersity 1.1), to synthesize block copolymers. The prepared nanoparticles had a mean particle size of about 140 nm with a zeta potential of about -20 mV. The results obtained by the TEM and AFM examinations showed that the morphology of the prepared nanoparticles was spherical in shape with a smooth surface. In the stability study, no aggregation or precipitation of nanoparticles was observed during storage for up to 1 month, as a result of the electrostatic repulsion between the negatively charged nanoparticles. With increasing the galactosamine content conjugated on the rhodamine-123-containing nanoparticles, the intensity of fluorescence observed in HepG2 cells increased significantly. Additionally, the intensity of fluorescence observed in HepG2 cells incubated with the nanoparticles with or without galactosamine conjugated increased approximately linearly with increasing the duration of incubation. In contrast, there was no fluorescence observed in Hs68 cells (without ASGP receptors) incubated with the nanoparticles with galactosamine conjugated. The aforementioned results indicated that the galactosylated nanoparticles prepared in the study had a specific interaction with HepG2 cells via ligand-receptor recognition.
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PMID:Preparation of nanoparticles composed of poly(gamma-glutamic acid)-poly(lactide) block copolymers and evaluation of their uptake by HepG2 cells. 1591 30

Bone substitutes have been used for the treatment of bone defects. The objective of this study was to ultrastructurally evaluate the healing pattern of bone defects filled with a copolymer of polylactic/polyglycolic acid (FisiograftR) at a time point in which it is expected to be only partially degraded, with the purpose to ultrastructurally analyze how the bone is forming around the grafting material. Three 5-mm-diameter bone defects were created in each tibia from 5 rabbits (average weight 2.5 kg) in which the material was randomly implanted. Animals were sacrificed 30 days after surgery and the 30 bone defects were fixed in 2% glutaraldehyde-2.5% formaldehyde, under microwave irradiation, decalcified in EDTA, embedded in Spurr resin, and examined in a Jeol 1010 TEM. All the bone defects were filled with connective tissue, interspersed with different amounts of the filling material and newly formed bone trabeculae. In areas where the degrading copolymer was present in small amounts, newly formed bone matrix was detected; it was deposited by osteoblast-like cells in close relation to the copolymer. In areas where the degrading copolymer formed accumulates, an amorphous multilayered material was identified between the connective tissue and the copolymer. In summary, the copolymer of PLA/PGA studied appears to be an osteoconductive material when it is used to fill bone defects.
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PMID:Ultrastructure of bone healing in defects grafted with a copolymer of polylactic/polyglycolic acids. 1594 3

The aim of this study was to report on the clinical and radiographic results 5 years following treatment of intrabony defects with guided tissue regeneration (GTR) in combination with deproteinized bovine bone (DBB) (Bio-Oss). Fifteen patients, with at least one intrabony periodontal defect with probing pocket depth (PPD)>or=7 mm and radiographic presence of an intrabony component (IC)>or=4 mm, were treated with a PLA/PGA bioabsorbable membrane. Prior to placement of the membrane, the defect was filled with DBB impregnated with gentamicin sulfate 2 mg/ml. Standardized intraoral radiographs were taken prior to treatment and at the control examinations after 1 and 5 years. At baseline, the average PPD was 9.2+/-1.1 mm, and the average probing attachment level (PAL) was 10.1+/-1.6 mm; the radiographic bone level (RBL) was 10.4+/-2.45 mm, and an IC of 6.2+/-2.3 mm was present. One year after membrane placement, treatment had resulted in a PAL gain of 3.8+/-1.8 mm, a residual PPD of 4.2+/-1.3 mm, an RBL gain of 4.7+/-2.0 mm, and a residual IC of 2.1+/-1.2 mm. At the 5-year examination, two patients did not show up, and two patients had lost the treated tooth. However, both teeth were endodontically treated, and progressive periodontal destruction might not necessarily have been the reason for extraction. At the 5-year control (11 patients), the PAL gain was 4.1+/-1.6 mm, and the residual PPD was 4.6+/-1.2 mm; an RBL gain of 4.9+/-2.7 mm and a residual IC of 1.8+/-0.8 mm were observed. Statistically significant clinical improvements had occurred between baseline and the 1- and 5-year controls, whereas there were no significant differences between the 1- and 5-year results. The results of GTR with bioabsorbable membranes in combination with Bio-Oss in the treatment of periodontal intrabony defects are basically stable on a long-term basis.
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PMID:Five-year results of guided tissue regeneration in combination with deproteinized bovine bone (Bio-Oss) in the treatment of intrabony periodontal defects: a case series report. 1601 May 81

The work aims to provide a histological investigation of Fisiograft, a PLA/PGA copolymer, used as filler for bone defects in humans. The study was performed on biopsies of sinus lifts where Bio-Oss and Fisiograft gel were applied as graft material. Bone regeneration was satisfactory in all sinus lifts, even when Fisiograft was applied alone. Due to remarkable osteoclast activity, Bio-Oss granules were cleared from the majority of biopsy cores. At histology, Fisiograft gel appeared as globes enveloped by fibroblasts, displaying an epithelial-like cell appearance. Due to its solubility in solvents, undegraded Fisiograft (recorded for 7 months or more) did not stain whereas degraded Fisiograft stained positive. The loose connective tissue, that surrounded Fisiograft and bone contained isolated mastocytes. Bone grew inside the loose connective and often reached the surface of Fisiograft by intervening cells. The results seem to indicate that Fisiograft may be considered both a polymer useful for fastening bone substitutes inside a defect and in addition a material capable of prompting bone regeneration, with or without the use of a bone substitute. In addition to space-former and space-maintainer functions, Fisiograft shows potential bone stimulation function, which may be labelled as osteopromotive capability.
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PMID:Histological study on sinus lift grafting by Fisiograft and Bio-Oss. 1616 6

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

Surface hydrolysis of polyester scaffolds is a convenient technique suggested to promote protein adsorption for improving cell attachment. We have, therefore, investigated the effect of hydrolysis of polyester surfaces for protein adsorption to clarify the conditions needed. Three polyesters, poly(ethylene terephthalate) (PET), poly(lactic acid) (PLA), and poly(glycolic acid) (PGA), were selected. Adsorption was investigated by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and quartz crystal microbalance (QCM). Hydrolyzed PET adsorbed significantly more proteins than nonhydrolyzed. Degradable polymers adsorbed at higher rates when the polymers were hydrolyzed prior to adsorption, but the same amount as nonhydrolyzed, suggesting spontaneous hydrolysis during the adsorption. XPS shows that hydrolysis prior to absorption for PET results in a surface nitrogen composition of approximately 14%, similar to pure protein (16%). Nonhydrolyzed PET surfaces showed only approximately 7% nitrogen, indicating protein layers thinner than approximately 10 nm. Adsorption to PLA and PGA shows nitrogen contents of 14-15% in both cases. SEM revealed striking differences in morphology of the protein coating. Hydrolyzed or spontaneously hydrolyzable surfaces display a pronounced fibrous structure while nonhydrolyzed surfaces give smooth structures. In combination, the results show that surface hydrolysis increase adsorption rate, but not the amount of proteins on polyesters that degrades in vivo. Surface treatment of nondegradable polyester increases the total amount of proteins and induces the formation of fibrous protein structures. Post hydrolysis treatment by acetic acid, replacing the counter-ion to a proton, further enhances protein attachment. Finally, cell attachment experiments verifies that protein adsorption increase the cell attachment to polyester surfaces.
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PMID:Protein adsorption onto polyester surfaces: is there a need for surface activation? 1668 Jun 92

We characterize the infiltration of interstitial cells into tissue engineering scaffolds prepared with electrospun collagen, electrospun gelatin, electrospun poly(glycolic) acid (PGA), electrospun poly(lactic) acid (PLA), and an electrospun PGA/PLA co-polymer. Electrospinning conditions were optimized to produce non-woven tissue engineering scaffolds composed of individual fibrils less than 1000 nm in diameter. Each of these materials was then electrospun into a cylindrical construct with a 2 mm inside diameter with a wall thickness of 200-250 microm. Electrospun scaffolds of collagen were rapidly, and densely, infiltrated by interstitial and endothelial cells when implanted into the interstitial space of the rat vastus lateralis muscle. Functional blood vessels were evident within 7 days. In contrast, implants composed of electrospun gelatin or the bio-resorbable synthetic polymers were not infiltrated to any great extent and induced fibrosis. Our data suggests that topographical features, unique to the electrospun collagen fibril, promote cell migration and capillary formation.
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PMID:Regulation of cellular infiltration into tissue engineering scaffolds composed of submicron diameter fibrils produced by electrospinning. 1670 19

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

Conventional micromolding provides rapid and low-cost methods to fabricate polymer microstructures, but has limitations when producing sophisticated designs. To provide more versatile micromolding techniques, we developed methods based on filling micromolds with polymer microparticles, as opposed to polymer melts, to produce microstructures composed of multiple materials, having complex geometries, and made using mild processing conditions. Polymer microparticles of 1 to 30 microm in size were made from PLA, PGA and PLGA using established spray drying and emulsion techniques either with or without encapsulating model drug compounds. These polymer microparticles were filled into PDMS micromolds at room temperature and melted or bonded together to form microstructures according to different protocols. Porous microstructures were fabricated by ultrasonically welding microparticles together in the mold while maintaining the voids inherent in their packing structure. Multi-layered microstructures were fabricated to have different compositions of polymers and encapsulated compounds located in different regions of the microstructures. More complex arrowhead microstructures were fabricated in a two-step process using a single mold. To assess possible applications, microstructures were designed as microneedles for minimally invasive drug delivery. Multi-layer microneedles were shown to insert into cadaver tissue and, according to design, detach from their base substrate and remain embedded in the tissue for controlled release drug delivery over time. We conclude that polymer particle-based micromolding can encapsulate compounds within microstructures composed of multiple materials, having complex geometries, and made using mild processing conditions.
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PMID:Polymer particle-based micromolding to fabricate novel microstructures. 1719 10

The purpose of this study was to evaluate host response and soft-tissue regeneration after poly(lactic acid) (PLA) mesh implantation in a rat model, in comparison with light-weight polypropylene (PPL) and poly(glycolic acid) (PGA) meshes. Full-thickness abdominal wall defects were created in 45 Wistar rats and reconstructed with 15 PLA(94), 15 PPL and 15 PGA meshes. Animals were killed on days 7, 30 and 90 to evaluate the presence of adhesions and changes in tensile strength of the implants. Histopathology and immunohistochemistry were performed to evaluate the collagen deposition and the inflammatory response. Statistics were done using unpaired Student's t-test, Mann-Whitney rank sum test, Student-Newman-Keuls test and Bonferroni (Dunn) t-test. The inflammatory response induced by the PLA mesh implantation was significantly milder than after PPL mesh. In PLA, vascularity and collagen organization was significantly higher than in PPL and PGA at 30 and 90 days, and collagen composition score was significantly higher than in PPL at 7 and 30 days. In PLA, shrinkage was significantly lower than in PPL and PGA at 7 and 30 days. Elongation at break and tensile strength were comparable between PLA and PPL over the 90-day period. The PLA mesh induces a milder inflammatory response, more orderly collagen deposition than PPL, and preserved comparable tensile strength after 90 days.
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PMID:Long-lasting bioresorbable poly(lactic acid) (PLA94) mesh: a new approach for soft tissue reinforcement based on an experimental pilot study. 1721 29


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