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Biomedical subjects

Shenguo Wang

Publications and source records attributed to Shenguo Wang.

At least 19 recordsLinked to original sources

The effect of oxygen plasma pretreatment and incubation in modified simulated body fluids on the formation of bone-like apatite on poly(lactide-co-glycolide) (70/30).

In this study, biodegradable poly(lactide-co-glycolide) (PLGA) (70/30) films and scaffolds were first treated with oxygen plasma and then incubated in a modified simulated body fluid 1.5SBF0 to prepare a bone-like apatite layer. The formation of the apatite and its influence on osteoblast-like cells growth were investigated. It was found that the bone-like apatite formability of PLGA(70/30) was enhanced by plasma pretreatment. The changes of surface chemistry and surface topography induced by oxygen plasma treatment were both effective for apatite formation. The apatite formability increased with increasing plasma-treating time. Under a treating condition of 20 W for 30 min, oxygen plasma treatment could penetrate into the inner scaffold. After 6 days incubation, the apatite formed in plasma-treated scaffold was better distributed than in untreated scaffold, and the weight and mechanical strength of the plasma-treated scaffold were both enhanced. Compared with PLGA(70/30), the apatite layer formed on oxygen plasma-treated PLGA(70/30) surface enhanced adhesion and proliferation of OCT-1 osteoblast-like cell, but had no significant effect on cell's ALP activity at day 7. A prolonged investigation is being in process to further verify the bone-like apatite effects on osteogenic differentiation.

Apatites↗

Manufacturing and morphology structure of polylactide-type microtubules orientation-structured scaffolds.

Tissue engineering using scaffold not only should have biodegradability and a certain 3D structure, but also its morphology structure should be mimetic to that of the repaired natural tissue. So to manufacture the scaffold with a biomimetic structure as the natural tissues is important. In this research, highly porous poly(L-lactic acid) (PLLA) and poly(L-lactic-co-glycolic acid) (PLGA) scaffolds with microtubules orientation structure were designed and fabricated by using dioxane as solvent and an improved thermal-induced phase separation (TIPS) technique. All the factors which will affect solvent crystallization and microtubules orientation structure of the scaffold, such as the type of the solvent and polymer, concentration of the polymer solution, and temperature-gradient of the system have been studied carefully. So the porosity, diameter, tubular morphology and orientation of the microtubules could be controlled by adjusting the concentration of the polymer solution and temperature-gradient of the system. The scaffold with diameter of microtubules from 40 to 240microm and high porosity up to 96% could be obtained by adjusting temperature-gradient during the TIPS process. By increasing concentration of the polymer solution the regularity of the microtubular scaffold has been improved and the thickness of wall of the microtubules has been increased as well. In vitro cell culture results show that after the scaffolds have been improved by the ammonia plasma treatment and then collagen anchorage method, the human transparent cartilage cells H144, could be seeded deeply into the microtubules orientation-structured scaffolds and grew well there.

Biocompatible Materials↗

Influences of ammonia plasma treatment on modifying depth and degradation of poly(L-lactide) scaffolds.

Hydrophobicity of poly(L-lactide) scaffolds is a main drawback in obtaining a sufficient mass of seeded cells for satisfying the requirements of tissue engineering. Plasma treatment is a useful technique to enhance the hydrophilicity of the scaffolds. However, the effect of this technique on the modifying depth and degradation of the scaffolds should be considered. In this paper, the influence of NH3 plasma treatment on the modifying depth and degradation of scaffolds were investigated. The results showed that the modifying depth of the scaffolds increased with treating time and the plasma power ranging from 20 to 80 W influenced the depth slightly. However, the degradation of the scaffolds increased with increasing treatment time and plasma power. The results also showed that the plasma intruded the scaffolds gradually from top to bottom. For a 4 mm thick scaffold, the optimized treatment condition was 20 W of power in a 30 Pa ammonia atmosphere for 30 min of treating time. Under this condition, the integrity of scaffold could be relatively well kept. NH3 plasma treatment enabled the penetration of cells into scaffolds and facilitated the proliferation of cells in them.

3T3 Cells↗

In vitro homogeneous and heterogeneous degradation of poly(epsilon-caprolactone/polyethylene glycol/L-lactide): The absence of autocatalysis and the role of enzymes.

This study investigated the in vitro degradation behavior of poly(epsilon-caprolactone/polyethylene glycol/L-lactide) (PCEL) in comparison with that of three other biodegradable polymers. Polymer membranes were incubated in pancreatin solution, Ringer's solution, and distilled water at 37 degrees C for up to 20 weeks. Characterization involved measuring weight loss, observing the morphological changes by scanning electron microscopy (SEM), analyzing molecular weight using size exclusion chromatography (SEC), and studying the crystalline structure using differential scanning calorimetry (DSC). The hydrolysis in a simple aqueous solution experienced no autocatalysis, which was attributed to the high permeability of PCEL to water-soluble degradation products. Similar degradation rates were recorded for the PCEL and poly(L,L-lactide) (PLLA) test membranes. In the presence of pancreatin, the PCEL membrane experienced rapid heterogeneous surface erosion likely caused by the selective loss of its surface PEG components under enzymatic action. Pancreatin also substantially increased the even physical resorption of the other test polymers by eliminating autocatalysis. This study demonstrated that autocatalysis commonly experienced by poly(alpha-hydroxyl acid) can be reduced through chemical formulation or high enzyme activity.

Biocompatible Materials↗

Porcine-derived xenogeneic bone/poly(glycolide-co-lactide-co-caprolactone) composite and its affinity with rat OCT-1 osteoblast-like cells.

Porcine-derived xenogeneic bone (PDXB) was derived from cancellous bone of adult porcine. Its morphology and structure were characterized by SEM, FTIR and XRD. A series of composite films consisting of PDXB and poly(glycolide-co-lactide-co-caprolactone) (PGLC) polymer were prepared. Because of the introduction of PGLC polymer, the PDXB/PGLC composites especially PDXB/PGLC(30/70) and PDXB/PGLC(50/50) showed good processability and mechanical properties. In addition, the hydrophilicity of the composites was enhanced as well since the PDXB component was hydrophilic. Osteoblast-like cells (OCT-1) were used as an in-vitro model to assess the affinity of the PDXB/PGLC composites. It was found that compared with the pure PGLC film, PDXB/PGLC(30/70) and PDXB/PGLC(50/50) composite films promoted cell attachment, proliferation and ALP (alkaline phosphatase) activity obviously. In addition, the cells preferred growing on the areas of exposed PDXB. It was considered that the hydrophilicity, osteoconductivity and appropriate surface roughness (Sa=3.30, 4.00 microm) induced by PDXB facilitate cell growth. However, the introduction of too much PDXB, such as PDXB/PGLC(70/30) film, would obtain an adverse effect on the cell growth since the value of Sa was up to 7.33 microm. It indicated that only the composites with appropriate surface topography could favor cell growth. Surface topography probably has a more important effect on cell growth process than surface chemistry.

Animals↗

Prevention of experimental proliferative vitreoretinopathy with a biodegradable intravitreal drug delivery system of all-trans retinoic acid.

PURPOSE: To evaluate the antiproliferative effect of an all-trans retinoic acid (at-RA) drug delivery system (DDS) on experimental proliferative vitreoretinopathy (PVR). METHODS: PVR was induced in rabbits with core vitrectomy and fibroblast injection. The DDS containing 420 microg, 650 microg, and 1,070 microg of at-RA was implanted into the vitreous of treated groups B, C, and D, respectively. Group A with no DDS and group E with nonmedicated DDS served as controls. The intravitreal at-RA concentration was measured with high-pressure liquid chromatography. The drug toxicity was evaluated histologically. RESULTS: The severity of PVR was significantly reduced in groups C and D but not in groups A, B, and E. The drug release peaked at 6 weeks to 7 weeks. No signs of retinal toxicity were found in the DDS groups. CONCLUSION: Intravitreal implantation of at-RA DDS appears effective in inhibiting the development of PVR and is well tolerated in rabbit eyes.

Absorbable Implants↗

Sustained intraocular rapamycin delivery effectively prevents high-risk corneal allograft rejection and neovascularization in rabbits.

PURPOSE: To evaluate the immunosuppressive and antiangiogenic activities of an intraocular rapamycin (RAPA) drug delivery system (DDS) in a rabbit model of high-risk penetrating keratoplasty. METHODS: Forty New Zealand White rabbits with corneal neovascularization underwent allograft cornea transplantation and were randomly divided into four groups: a control group, a glycolide-co-lactide-co-caprolactone copolymer (PGLC)-implanted group, a RAPA eye drop group, and a RAPA-PGLC DDS-implanted group. Graft survival, corneal neovascularization, and RAPA concentration in the aqueous humor were monitored for 90 days. Corneal grafts were also examined by in situ hybridization and immunohistochemistry for proinflammatory gene expression. RESULTS: In the control and PGLC groups, graft rejection occurred within 3 weeks of keratoplasty. In the RAPA eye drop and RAPA-PGLC groups, corneal rejection was significantly delayed, and neovascularization was markedly inhibited. Median graft survival times were 36 and >90 days in the eye drop and RAPA-PGLC groups, respectively. Mean RAPA concentrations in the aqueous humor were 10.7 ng/mL, 12.0 ng/mL, 9.2 ng/mL, and 7.0 ng/mL in the RAPA-PGLC group 2, 4, 8, and 12 weeks after surgery, respectively. By contrast, RAPA was undetectable in the aqueous humor in the eye drop group. High levels of IL-2R, MCP-1, TNF-alpha, and VEGF were detected in the corneal grafts of the control and PGLC groups but not in those of the RAPA-treated groups. CONCLUSIONS: RAPA-PGLC DDS and RAPA eye drops can significantly prolong the survival of allografts at high risk and inhibit corneal neovascularization. However, RAPA-PGLC DDS is far more effective than RAPA eye drops in preventing corneal graft rejection.

Animals↗

Intravitreal implantation of the biodegradable cyclosporin A drug delivery system for experimental chronic uveitis.

PURPOSE: The purpose was to evaluate the efficacy of the intravitreal implantation of the biodegradable cyclosporin A (CsA) drug delivery system (DDS) for experimental chronic uveitis. METHODS: The DDS was prepared by formulating CsA into glycolide-co-lactide-co-caprolactone copolymer (PGLC). Right eyes of 30 New Zealand white rabbits were used to establish a model of uveitis and randomized into control, intravitreal non-medicated DDS, oral CsA (15 mg/kg daily), and intravitreal CsA-PGLC DDS (each containing 2 mg CsA) groups. The progress of ocular inflammation, results of electroretinography, and histopathological examination of ocular, renal, and hepatic functions were recorded. Intravitreal CsA levels were measured in another 13 rabbits receiving an implant of the CsA-PGLC DDS. RESULTS: Chronic uveitis was successfully induced in all 30 eyes. The inflammation in the eyes with no treatment, non-medicated implant, and oral CsA was more severe than those with the CsA-PGLC DDS at each timepoint. The electroretinography b-wave was depressed much less in the CsA-PGLC DDS group than in the other three groups (p<0.05). No renal or hepatic tissue damage was found in eyes with the CsA-PGLC DDS. The mean intravitreal CsA level was 102.2~145.5 ng/ml at 1~3 weeks after CsA-PGLC DDS implantation, 491.0~575.2 ng/ml at 4~10 weeks, and 257.3 ng/ml at 14 weeks; no toxicity was detected. CONCLUSION: Intravitreal implantation of the biodegradable CsA-PGLC DDS may effectively reduce the intraocular inflammation in rabbits with no toxicity, which provides a potentially safe and convenient approach for the treatment of chronic uveitis.

Absorbable Implants↗

Bulk and surface modifications of polylactide.

This article reviews various methods of modifying the bulk and surface properties of poly(lactic acid) (PLA) so that the polymer may be used as a drug carrier in a drug delivery system (DDS) and as a cell scaffold in tissue engineering. Copolymerization of lactide with other lactone-type monomers or monomers with functional groups such as malic acid, copolymerization of lactide with macromolecular monomer such as poly(ethylene glycol) (PEG) or dextran, as well as blending polylactide and natural derivatives and other methods of bulk modification are discussed. Surface modifications of PLA-type copolymers, such as surface coating, chemical modification, and plasma treatment are described. Cell culture technology proves the efficiency of bulk and surface modification and the potential application of PLA in tissue engineering.

Absorbable Implants↗

Preparation and evaluation of poly(L-lactide-co-glycolide) (PLGA) microbubbles as a contrast agent for myocardial contrast echocardiography.

A kind of absorbable PLGA microbubble-based contrast agent (PLGA microspheres with porous or hollow inner structure) was fabricated by an improved double emulsion-solvent evaporation method. The contrast efficiency was evaluated and proved both in vitro and in vivo. By adjusting the polymer concentration and volume of the inner aqueous phase during the fabrication of microbubbles, the inner structure of the microbubbles could be controlled. Both air-filled and perfluoropropane-filled microbubbles can opacify the left ventricle. However, when compared with air-filled microbubbles, perfluoropropane-filled microbubbles can produce significantly longer enhancement in left ventricle in the dog model due to the lower diffusivity and lower solubility of perfluoropropane in blood. A suspension of perfluoropropane-filled PLGA microbubbles (1.8 microm average microbubbles size, 2 x 10(8) microbubbles/mL concentration) has successfully and safely achieved myocardial opacification in closed-chest dogs. A perfusion defect was observed in both of the two dogs with acute myocardial infarction with Power Contrast Imaging (PCI) triggered technology. In the examination of contrast in both ventricular and myocardial opacification, the high mechanical index (MI) was found to have superior contrast sensitivity over the low MI for PLGA-based contrast agents.

Acoustics↗

Adhesion and proliferation of OCT-1 osteoblast-like cells on micro- and nano-scale topography structured poly(L-lactide).

The impact of the surface topography of polylactone-type polymer on cell adhesion was to be concerned because the micro-scale texture of a surface can provide a significant effect on the adhesion behavior of cells on the surface. Especially for the application of tissue engineering scaffold, the pore size could have an influence on cell in-growth and subsequent proliferation. Micro-fabrication technology was used to generate specific topography to investigate the relationship between the cells and surface. In this study the pits-patterned surfaces of polystyrene (PS) film with diameters 2.2 and 0.45 microm were prepared by phase-separation, and the corresponding scale islands-patterned PLLA surface was prepared by a molding technique using the pits-patterned PS as a template. The adhesion and proliferation behavior of OCT-1 osteoblast-like cells morphology on the pits- and islands-patterned surface were characterized by SEM observation, cell attachment efficiency measurement and MTT assay. The results showed that the cell adhesion could be enhanced on PLLA and PS surface with nano-scale and micro-scale roughness compared to the smooth surfaces of the PLLA and PS. The OCT-1 osteoblast-like cells could grow along the surface with two different size islands of PLLA and grow inside the micro-scale pits of the PS. However, the proliferation of cells on the micro- and nano-scale patterned surface has not been enhanced compared with the controlled smooth surface.

Animals↗

FK506 in a biodegradable glycolide-co-clatide-co-caprolactone polymer for prolongation of corneal allograft survival.

PURPOSE: FK506 has been extensively used in preventing immune rejection for human organ transplantation. This study aimed to evaluate the effects of a biodegradable FK506 drug delivery system (DDS) implanted into anterior chamber for the prolongation of corneal allograft survival in high-risk keratoplasty. METHODS: Biodegradable glycolide-co-clatide-co-caprolactone polymer (PGLC) was used as drug carrier to be incorporated with 0.5 mg of FK506 powder. The drug release from the FK506-PGLC DDS was evaluated in vitro and in vivo. The FK506-PGLC DDS was implanted into the anterior chamber of 12 high-risk keratoplasty rabbits. The graft survival time and clinical features of the FK506-PGLC DDS group were compared with the untreated, PGLC DDS, cyclosporin A-PGLC DDS, and 0.5% FK506 drops groups. The histopathological examination was performed to evaluate the safety of the FK506-PGLC DDS. RESULTS: The mean graft survival time was longest (> 180 days) in the FK506-PGLC DDS group. In vivo, the FK506 concentration in aqueous humor peaked on day 28 (17.9 +/- 2.3 ng/ml) and kept a sustained release for at least 168 days. No adverse reactions were observed in the FK506-PGLC DDS group. CONCLUSIONS: Biodegradable FK506-PGLC DDS implanted into anterior chamber can effectively prevent immune rejection in high-risk keratoplasty model, presenting a promising approach for the prolongation of corneal allograft survival.

Absorbable Implants↗

Erosion induced controllable release of gliclazide encapsulated inside degradable polymeric particles.

The microphase inversion of water-insoluble poly(L-lactide), "poly[(L-lactide)-co-glycolide] and polylactide-block-poly(ethylene oxide)-block-polylactide from THF to water can result in narrowly distributed stable particles. Gliclazide, a commercial drug, can be encapsulated inside during the process. The formation and degradation of such particles was studied by laser light scattering. In comparison with the corrosion of a bulk material, the degradation of each particle is so fast that we only detect the decrease of the particle number, not the corrosion of individual particles. Therefore, the degradation is a "one-by-one" random process, just like the chemical reaction of molecules in solution. The disappearing rate of the particle number is nearly independent of time, ideal for the controlled release of drugs encapsulated inside. The amount of encapsulated gliclazide depends on the copolymer's hydrophobicity (composition), while the releasing rate mainly is, directly related to the disappearing rate of the particles. The correlation between the fluorescence intensity and the degradation was used to study the kinetics of gliclazide releasing. The releasing pattern is controllable with a proper choice of the drug loading, copolymer composition, pH and temperature.

Biodegradation, Environmental↗

Characterization of surface property of poly(lactide-co-glycolide) after oxygen plasma treatment.

In this study, poly (lactide-co-glycolide) (PLGA) films were treated by oxygen plasma. The surface structure, topography and surface chemistry of treated PLGA films were characterized by contact angle measurement, scanning electron microscope observation, atomic force microscopy, and X-ray photoelectron spectrum analysis. The cell affinity of the oxygen plasma treated films was evaluated under dynamic conditions by Parallel Plate Flow Chamber (PPFC). The results showed that the hydrophilicity increased greatly after oxygen plasma treatment. High quantities of -C-O groups, such as hydroxyl and peroxyl groups could be incorporated into the surface of PLGA (70/30) by controlling appropriate plasma treatment conditions. Moreover, the oxygen plasma treatment resulted in formation of peaks and valleys on the sample surfaces, and the roughness increased with treatment time. Cells stretched very well and the ability to endure the shear stress was improved greatly after the PLGA (70/30) was modified by appropriate plasma treatment, i.e. under 50W for 2 or 10 min. However, when the treatment time was increased to 20 min, the percentage of adherent cells on the roughest surface decreased because the content of polar groups incorporated onto the surface decreased. The results showed that improved cell adhesion was attributed to the combination of surface chemistry and surface morphology of PLGA during plasma etching.

Animals↗

Synthesis and cell affinity of functionalized poly(L-lactide-co-beta-malic acid) with high molecular weight.

A novel functionalized biodegradable poly(L-lactide-co-beta-benzyl malolactonate) (p-PLMA) with high molecular weight was synthesized through ring-opening copolymerization. Three p-PLMA copolymers with different beta-benzyl malolactonate content were synthesized. The molecular weight (M(w)) and tensile strength of the copolymer with 4 mol% beta-benzyl malolactonate content were 179,800 and 19.0MPa respectively, the molecular weight (M(w)) and tensile strength of p-PLMA decreased with beta-benzyl malolactonate content increasing. The hydrophilicity of the de-protected product: poly(L-lactide-co-beta-malic acid) (d-PLMA) increased with malic acid content increasing. The results of 3T3 mice fibroblasts cultivated on d-PLMA films showed that the cell adhesion on d-PLMA was better than that of PLLA and the cell attached efficiency of d-PLMA with 8 mol% malic acid content was the highest. The cells grew well both on the surface and inside of d-PLMA scaffolds. The cell affinity of d-PLMA was better than that of PLLA.

3T3 Cells↗

Plasma-treated, collagen-anchored polylactone: Its cell affinity evaluation under shear or shear-free conditions.

Poly(L-lactic acid)(PLLA) and poly(L-lactic-co-glycolic acid) (PLGA) (85/15) were modified by plasma treatment. Then they were collagen anchored (PT/CA), and the cell affinity was evaluated by cell culture under shear or shear-free conditions. A convenient and "intuitionistic" dyeing method has been proposed for measuring the modified depth when plasma treatment is applied for the treatment of porous scaffolds. A parallel plate flow chamber was developed in order to study the cell affinity of a material under shear stress. Our results show that a porous scaffold can be modified by plasma treatment and that a depth of about 4.0 mm for this modification can be reached with NH(3) plasma treatment (50 w, 20 Pa, 5 min). PT/CA modification is an effective surface modification method for facilitating cell transplantation and improving the cell affinity of three-dimensional porous cell scaffolds in tissue engineering. It can solve the problem of non-uniform cell distribution in most synthetic porous cell scaffolds. Using the flow chamber system, a series of quantitative data, including cell adherent fraction, cell area, and mean shape, were compared to evaluate the cell affinity of PLLA before and after PT/CA modification. The results indicate that the quality of cell attachment on PT/CA-modified PLLA apparently is better than that on unmodified PLLA. The flow chamber system potentially may be a tool for evaluating surface modification methods.

3T3 Cells↗

Acceleration effect of basic fibroblast growth factor on the regeneration of peripheral nerve through a 15-mm gap.

In this study, nerve guides composed of poly(D,L-lactide) (PDLLA) were fabricated and used in the repair of transected sciatic nerves (15-mm gaps) of rats. Nerve guides with a two-ply structure (inner layer dense, outer layer microporous) were prepared by controlling the solvent evaporation rate. Then basic fibroblast growth factor (bFGF) was embedded in the inner layer of the nerve guides. Thus the inner dense layer not only could prevent the ingrowth of fibroblast and avoid the outgrowing nerve cable, but it also could retain the released bFGF in the guide lumen. The outer porous layer allowed vascular ingrowth and the diffusion of essential nutrients into the guide lumen. The data show that by using this nerve guide, the transected 15-mm sciatic nerve was regenerated successfully within 4 months. The recovery of function of the regenerated nerves was significantly accelerated by bFGF, as indicated by an electrostimulation test and histologic assays. In addition, the bFGF retained its bioactivity during embedding and continuously was released from the matrix, as confirmed by the results of both the dorsal root ganglia (DRG) and the Schwann cell culture in the presence of PDLLA matrix containing bFGF. The released bFGF enhanced the ability of the nerve fibers to sprout from dorsal root ganglia, and it accelerated the proliferation of Schwann cells.

Animals↗

Enzymatic degradation behavior and mechanism of poly(lactide-co-glycolide) foams by trypsin.

The purpose of this study is to investigate the enzymatic degradation behaviors of porous poly(lactide-co-glycolide) (PLGA) foams in the presence of trypsin, in comparison with their hydrolytic degradation. To inspect the effect of trypsin on the degradation of PLGA, both the hydrolytic and enzymatic degradation of non-porous PLGA samples were also performed. The changes of molecular weight and molecular weight distribution (polydispersity) during the degradation were determined by gel permeation chromatograph. And the changes of weight, thickness and morphology with the degradation were also measured. The degradation of PLGA displayed as two stages. In the first stage, the molecular weight of PLGA decreased continuously with degradation time, whereas little weight loss occurred. But in the second stage, the molecular weight of PLGA had decreased to a low value and was almost unchanged with time, while the sample experienced significant weight loss. And it was found that the presence of trypsin could significantly accelerate the weight loss rates of all the PLGA samples, but it caused little difference in the decrease of molecular weight and the change of PLGA composition between the enzymatic and hydrolytic degradation. Therefore, the enzymatic degradation of PLGA was still primarily a hydrolysis process. A mechanism of enzymatic degradation was proposed that the trypsin could enhance the weight loss of PLGA by acting as surfactant to push the dispersion of degradation products into water even though they could not dissolve in water.

Biocompatible Materials↗