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)

Poly(epsilon-caprolactone) (PCL) microspheres containing c. 3% bovine serum albumin (BSA) were prepared by melt encapsulation and solvent evaporation techniques. PCL, because of its low Tm, enabled the melt encapsulation of BSA at 75 degrees C thereby avoiding potentially toxic organic solvents such as dichloromethane (DCM). Unlike the solvent evaporation method, melt encapsulation led to 100% incorporation efficiency which is a key factor in the microencapsulation of water-soluble drugs. Examination of the stability of the encapsulated protein by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that protein integrity was unaffected by both methods of encapsulation. In vitro release of the protein into phosphate buffer examined at 37 degrees C from microspheres prepared by both techniques showed that the release rate from melt-encapsulated microspheres was somewhat slower compared to the release from solvent-evaporated spheres. Both released around 20% of the incorporated protein in 2 weeks amounting to approximately 6.5 micrograms mg-1 of microspheres. Although the diffusivity of macromolecules in PCL is rather low, it is shown that PCL microspheres are capable of delivering sufficient quantity of proteins by diffusion for prolonged periods to function as a carrier for many vaccines. Unlike poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) polymers which generate extreme acid environments during their degradation, the delayed degradation characteristics of PCL do not generate an acid environment during protein release and, therefore, may be advantageous for sustained delivery of proteins and polypeptides.
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PMID:Protein release from poly(epsilon-caprolactone) microspheres prepared by melt encapsulation and solvent evaporation techniques: a comparative study. 915 Nov 93

Bioabsorbable polymer implants may provide a viable alternative to metal implants for internal fracture fixation. One of the potential difficulties with absorbable implants is the possible toxicity of the polymeric degradation products especially if they accumulate and become concentrated. Accordingly, material evaluation must involve dose-response toxicity data as well as mechanical properties and degradation rates. In this study the toxicity and rates of degradation for six polymers were determined, along with the toxicity of their degradation product components. The polymers studied were poly(glycolic acid) (PGA), two samples of poly(L-lactic acid) (PLA) having different molecular weights, poly(ortho ester) (POE), poly(epsilon-caprolactone) (PCL), and poly(hydroxy butyrate valerate) (5% valerate) (PHBV). Polymeric specimens were incubated at 37 degrees C in 0.05 M Tris buffer (pH 7.4 at 37 degrees C) and sterile deionized water. The solutions were not changed during the incubation intervals, providing a worst-case model of the effects of accumulation of degradation products. The pH and acute toxicity of the incubation solutions and the mass loss and logarithmic viscosity number of the polymer samples were measured at 10 days, 4, 8, 12, and 16 weeks. Toxicity was measured using a bioluminescent bacteria, acute toxicity assay system. The acute toxicity of pure PGA, PLA, POE, and PCL degradation product components was also determined. Degradation products for PHBV were not tested. PGA incubation solutions were toxic at 10 days and at all following intervals. The lower molecular weight PLA incubation solutions were not toxic in buffer but were toxic by 4 weeks in water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products. 1014 75

The effect of polymer chemistry on adhesion, proliferation, and morphology of human articular cartilage (HAC) chondrocytes was evaluated on synthetic degradable polymer films and tissue culture polystyrene (TCPS) as a control. Two-dimensional surfaces of poly(glycolide) (PGA), poly(L-lactide) (L-PLA), poly(D,L-lactide) (D,L-PLA), 85:15 poly(D,L-lactide-co-glycolide) (D,L-PLGA), poly(epsilon-caprolactone) (PCL), 90:10 (D,L-lactide-co-caprolactone) (D,L-PLCL), 9:91 D,L-PLCL, 40:60 L-PLCL, 67:33 poly(glycolide-co-trimethylene carbonate) (PGTMC), and poly(dioxanone) (PDO) were made by spin-casting into uniform thin films. Adhesion kinetics were studied using TCPS and PCL films and revealed that the rate of chondrocyte adhesion began to level off after 6 h. Degree of HAC chondrocyte adhesion was studied on all the substrates after 8 h, and ranged from 47 to 145% of the attachment found on TCPS. The greatest number of chondrocytes attached to PGA and 67:33 PGTMC polymer films, and attachment to PCL and L-PLA films was statistically lower than that found on PGA (p < 0.05). There was no correlation between amount of chondrocyte attachment to the substrates and the substrates' water contact angle. Chondrocytes proliferated equally well on all the substrates resulting in equivalent cell numbers on all the substrates at both day 4 and day 7 of the culture. However, these total cell numbers were reached as a result of a 88- and 42-fold expansion on PDO and PLA, respectively, which was significantly higher than the 11-fold expansion found on TCPS (p < 0.05). The greater fold expansion of the cells on PDO and L-PLA films may be attributed to the availability of space for cells to grow, since their numbers at the start of culture were fewer following the 8 h attachment period. This suggests that regardless of initial seeding density on these degradable polymer substrates (i.e., if some minimum number of cells are able to attach), they will eventually populate the surfaces of all these polymers given sufficient space and time.
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PMID:Human articular chondrocyte adhesion and proliferation on synthetic biodegradable polymer films. 1061 31

Several different bioabsorbable scaffolds designed and manufactured for guided bone regeneration and generation have been developed. In order to enhance the bioactivity and potential osteoconductivity of the scaffolds, different bioabsorbable polymers, composites of polymer and bioactive glass, and textured surface structures of the manufactured devices and composites were investigated in in vitro studies and experimental animal models. Solid, self-reinforced polyglycolide (SR-PGA) rods and self-reinforced poly L-lactide (SR-PLLA) rods were successfully used as scaffolds for bone formation in muscle by free tibial periosteal grafts in animal experiments. In an experimental maxillary cleft model, a bioabsorbable composite membrane of epsilon-caprolactone and L-lactic acid 50/50 copolymer (PCL/LLA) film and mesh and poly 96L,4D-lactide (PLA96) mesh were found to be suitable materials for guiding bone regeneration in the cleft defect area. The idea of solid layer and porous layer combined together was also transferred to stiff composite of poly 70L,30DL-lactide (PLA70) plate and PLA96 mesh which structure is introduced. The osteoconductivity of several different biodegradable composites of polymers and bioactive glass (BG) was shown by apatite formation in vitro. Three composites studied were self-reinforced composite of PLA70 and bioactive glass (SR-(PLA70 + BG)), SR-PLA70 plate coated with BG spheres, and Polyactive with BG.
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PMID:Bioabsorbable scaffolds for guided bone regeneration and generation. 1107 99

Tissue generation by autogenous cell transplantation is one of the most promising treatment concepts being developed as it eliminates problems of donor site scarcity, immune rejection and pathogen transfer. Cultured cells are seeded onto a three-dimensional biocompatible scaffold that will slowly degrade and resorb as the soft and hard structures grow and assimilate in vitro and/or in vivo. The 3-D scaffold provides the necessary template for cells to proliferate and maintain their differentiated state. Ultimately, it defines the overall shape of the tissue-engineered transplant. The aim of this review is to describe and discuss the scaffold materials of natural and synthetic origin that are of specific interest to tissue engineers. This review is based on previous publications and our own experience in the use of biomaterials of natural and synthetic origin for tissue engineering applications. Biodegradable polymers which have been used for tissue engineering applications are mainly based on clinically established medical devices and implants. In the group of macromolecules of natural origin collagen, alginate, agarose, hyaluronic acid derivatives, chitosan, and fibrin glue have been used as scaffolds. Man-made polymers such as polyglycolide (PGA), polylactides (PLLA, PDLA), poly(caprolactone) (PCL), and poly(dioxanone) (PDS) have been studied as matrix material to guide the differentiation and proliferation of cells into the targeted functional premature and/or mature tissue. Appropriate selection of scaffold material with respect to the targeted tissue is essential. Today, biomaterials of choice remain to be those approved by the US Food and Drug Administration. In spite of that, novel biomaterials should be developed specifically designed for tissue engineering applications.
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PMID:An introduction to biodegradable materials for tissue engineering applications. 1137 17

With this tissue engineering (TE) technique, the peripheral pulmonary artery was successfully reconstructed, using the patient's own venous cells in a 4-year-old girl, 2 years after Fontan procedure. A 4-year-old girl was given a diagnosis of single right ventricle, double-outlet right ventricle and pulmonary atresia. She underwent left modified Blalock-Taussig shunt at a month old, pulmonary artery angioplasty at a year and 3 months old, and bidirectional cavopulmonary shunt at 2 years and a month old. She underwent again pulmonary artery angioplasty and Fontan operation at 3 years and 3 months. An angiographical examination 7 months after the operation revealed total occlusion of the right intermediate pulmonary artery. TE technique using autologous cells was indicated. The application of this procedure was approved by the ethical committee in Tokyo Women's Medical University. The patient's parents were thoroughly informed and signed a consent form. Approximately 2 cm of the peripheral vein was explanted under sterile conditions. The tissue was minced, placed in tissue culture dishes and cultured at 37 degrees C, 100% humidity and a 5% CO2 atmosphere for almost a month. The number of cells substantially increased to reach 12 millions for almost a month. The culture medium was changed every 3 days. The polymer tube that served as a scaffold for cells was composed of the copolymer of PCL-PLA (50:50) with reinforcement by woven PGA. The polymer conduit, 10 mm in diameter, 20 mm in length and 1 mm in thickness, was designated to biodegradate within 8 weeks. The number of seeded cells was approximately a million/cm2. The graft transplantation was performed 10 days after seeding cells. The occlusive right intermediate pulmonary artery was reconstructed with the TE vessel graft under extracorporeal circulation with a pump-oxygenator. The patient followed a satisfactory postoperative course. The postoperative angiography demonstrated that the graft was not constricted and dilated but that it preserved good patency. Long-term follow-up are necessary. We plan to continue to use the TE technique using autologous cells in the low pressure system like venous or pulmonary circulation. Because our results even in early experimental phase were valuable and promising, we believe that the TE approach may play an important role in the near future as an another alternative, together with transplantation and artificial organ, especially in the field of cardiovascular surgery that mostly needs replants.
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PMID:[First successful clinical application of tissue engineered blood vessel]. 1199 17

For use in micro-patterned scaffolds in tissue engineering, novel diacrylated triblock macromers (PLA-b-PCL-b-PLA, PGA-b-PCL-b-PGA and PCL-b-PEO-b-PCL) were synthesized and characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR) and gel permeation chromatography (GPC). All diacrylated polymers were designed as triblock copolymers and involved biodegradable blocks of relatively non-polar epsilon-caprolactone (CL) and polar monomers such as glycolide (GA), lactide (LA) or ethylene oxide (EO). All triblock polymers were prepared in molecular weights of a few kilo daltons via the anionic ring-opening polymerization (ROP) of the corresponding lactide, glycolide or caprolactone using stannous octoate [Sn(Oct)(2)] as catalyst. The polymers had low polydispersity indices, ranging from 1.23 to 1.56. Biodegradable polymeric networks were prepared with conversions of 72-84% via photopolymerization of the triblock diacrylated polymers with 2,2-dimethoxy-2-phenylacetophenone (DMPA) as photoinitiator. PLA-b-PCL-b-PLA copolymers crumbled easily and were not suitable for micro-patterning. PGA-b-PCL-b-PGA copolymers had higher water contact angles than PCL-b-PEO-b-PCL and were also cytocompatible with Fibroblasts 3T3.
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PMID:Novel photopolymerizable biodegradable triblock polymers for tissue engineering scaffolds: synthesis and characterization. 1546 60

Recent advances in the synthesis of poly(gamma-butyrolactone) have yielded homopolymers of up to 50,000 Mw from the low-cost monomer gamma-butyrolactone. This monomer has for the better part of a century been thought impossible to polymerise. Poly(gamma-butyrolactone) displays properties that are ideal for tissue-engineering applications and the bacterially derived equivalent, poly(4-hydroxybutyrate) (P4HB), has been evaluated for such uses. The glass transition temperature (-48 to -51 degrees C), melting point (53-60 degrees C), tensile strength (50 MPa), Young's modulus (70 MPa) and elongation at break (1000%) of P4HB make it a very useful biomaterial. Poly(gamma-butyrolactone) degrades to give gamma-hydroxybutyric acid which is a naturally occurring metabolite in the body and it has been shown to be bioresorbable. Investigation into the synthesis of poly(gamma-butyrolactone) has recently produced homo-oligomeric diols 400-1000 Mw that are suitable for reacting with diisocyanates to form polyurethanes. Biodegradable polyurethanes made from diols of polyglycolide (PGA) and poly(epsilon-caprolactone) (PCL) have the disadvantage of high glass transition and slow degradation, respectively. Poly(gamma-butyrolactone) can be thought of as being the missing link in the biodegradable polyester family immediately between PGA and PCL and displaying intermediate properties.
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PMID:Chemosynthesis of bioresorbable poly(gamma-butyrolactone) by ring-opening polymerisation: a review. 1562 25

A series of copolymers with various compositions were synthesized by bulk ring-opening polymerization of glycolide and epsilon-caprolactone, using stannous (II) octoate or zirconium (IV) acetylacetonate as initiator. Reaction time and temperature were varied so as to induce different chain microstructures. The resulting copolymers were characterized by (1)H NMR, SEC, DSC, and X-ray diffraction. The average lengths of glycolyl (L(G)) and caproyl sequences (L(C)) and the degree of randomness (R) were calculated and compared to the values of completely random chains. The concentration of CGC sequences was also obtained which resulted from transesterification reactions. Data showed that stannous (II) octoate leads to less transesterification than zirconium (IV) acetylacetonate, and lower temperatures lead to less transesterification than higher ones. The copolymers exhibited a more or less blocky chain structure because of the reactivity difference between glycolide and epsilon-caprolactone. The crystalline structure and thermal properties depend on both the composition and the chain microstructure. PGA- and PCL-type crystallites were obtained for copolymers with intermediate compositions.
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PMID:Structure-property relationships of copolymers obtained by ring-opening polymerization of glycolide and epsilon-caprolactone. Part 1. Synthesis and characterization. 1563 56

Thin films of biodegradable polymeric materials, poly(epsilon-caprolactone) (PCL) and poly(glycolic acid) (PGA) were micro-patterned using a Ti-sapphire femtosecond pulsed laser and ArF excimer UV laser in ambient conditions. The laser-patterned polymers were characterized using a scanning electron microscope (SEM), Fourier transform infrared spectroscopy in attenuated total reflectance mode (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS). In-vitro degradation tests were performed and the laser-patterned samples showed to be within one standard deviation of the control samples. Our results demonstrate that both lasers are excellent tools for micro-patterning biodegradable polymers since the bulk properties of the material can remain intact and because the direct-write method is rapid, flexible, and a chemical-free process.
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PMID:Direct micro-patterning of biodegradable polymers using ultraviolet and femtosecond lasers. 1595 Feb 79


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