Medical-grade synthetic poly（lactic-co-glycolic acid） polymer can be used as a biomaterial for nerve repair because of its good biocompatibility, biodegradability and adjustable degradation rate. The stress relaxati...Medical-grade synthetic poly（lactic-co-glycolic acid） polymer can be used as a biomaterial for nerve repair because of its good biocompatibility, biodegradability and adjustable degradation rate. The stress relaxation and creep properties of peripheral nerve can be greatly improved by repair with poly（lactic-co-glycolic acid） tubes. ＂Fen sciatic nerve specimens were harvested from fresh corpses within 24 hours of death, and were prepared into sciatic nerve injury models by creating a 10 mm defect in each specimen. Defects were repaired by anastomosis with nerve autografts and poly（lactic-co-glycolic acid） tubes. Stress relaxation and creep testing showed that at 7 200 seconds the sciatic nerve anastomosed by poly（lactic-co-glycolic acid） tubes exhibited a greater decrease in stress and increase in strain than those anastomosed by nerve autografts. These findings suggest that poly（lactic-co-glycolic acid） exhibits good viscoelasticity to meet the biomechanical require- ments for a biomaterial used to repair sciatic nerve injury.展开更多
In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-...In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.展开更多
Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are compl...Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are complicated by contamination with ifbroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly puriifed Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells （〉95%） using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly（lactic-co-glycolic acid）/chi-tosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were signiifcantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental ifndings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly（lactic-co-glycolic acid）/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.展开更多
Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly（lactic-co-glycolic acid） conduit transplantation and autogenous nerve grafting for sciatic ner...Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly（lactic-co-glycolic acid） conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly（lactic-co-glycolic acid） conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly（lactic-co-glycolic acid） conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly（lactic-co-glycolic acid） conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly（lactic-co-glycolic acid） conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly（lactic-co-glycolic acid） conduits exhibited good intensity, elasticity and plasticity, indicating that poly（lactic-co-glycolic acid） conduits are suitable for sciatic nerve injury repair.展开更多
BACKGROUND： A degradable poly（lactic-co-glycolic acid） （PLGA） scaffold has been used to construct a degradable porous scaffold. This template can simulate the in vivo microenvironment and promote tissue formation...BACKGROUND： A degradable poly（lactic-co-glycolic acid） （PLGA） scaffold has been used to construct a degradable porous scaffold. This template can simulate the in vivo microenvironment and promote tissue formation. OBJECTIVE： To observe the histopathological changes during degeneration and regeneration of the intervertebral disc, and to analyze the effects of a PLGA scaffold on nerve fiber ingrowth into the lesion in vivo. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Orthopaedic Laboratory, Clinic Medical Research Institution, Sir Run Run Shaw Hospital, Zhejiang University, from December 2007 to July 2008. MATERIALS： PLGA （China Textile Academy）; growth-associated protein-43 （Life-span, USA）; and protein gene product 9.5 antibody （AbD, United Kingdom） were used in this study. METHODS： Three consecutive segments of the intervertebral disc of thirty-two healthy adult male New Zealand rabbits were exposed, comprising L3-4, L4-5 and L5-6. Experimental intervertebral disc （L4-5 and L5-6） models were established by two different methods. In the test （trephine ＋ scaffold） group, a 5-mm deep hole was drilled into the annulus fibrosus using a 3-mm diameter trephine, and the PLGA scaffold was implanted into the hole. In the acupuncture group, the remaining experimental intervertebral disc annulus fibrosus was damaged using a 16G needle at a depth of 5 mm. The L3-4 disc served as a control. MAIN OUTCOME MEASURES： Intervertebral disc degeneration was assessed using radiography, magnetic resonance imaging, and histological examination at various time points post-surgery. Nerve fiber ingrowth into the degenerated intervertebral disc was observed using immunohistochemical staining for growth-associated protein-43 and protein gene product 9.5. RESULTS： Compared with the normal controls, the heights of the damaged intervertebral discs were decreased, and T2 signal intensity was decreased in the test and acupuncture groups 2 weeks post-surgery. Intervertebral disc degeneration was faster in the test group than in the acupuncture group. PLGA was coated with newly formed tissue, gradually degraded, and absorbed, and could induce tissue ingrowth deep into the annulus fibrosus. Results of immunohistochemical staining showed that nerve fibers were distributed in newly formed tissue in the test group, and in the superficial layer or surrounding scar tissue in the acupuncture group. CONCLUSION： A porous PLGA scaffold provides an important biological channel to induce nerve fiber ingrowth deep into the degenerated intervertebral disc.展开更多
Objective: To prepare and characterize poly lactic-co-glycolic acid(PLGA) nanoparticles loaded with soluble leishmanial antigen or autoclaved leishmanial antigen and explore in vitro and in vivo immunogenicity of anti...Objective: To prepare and characterize poly lactic-co-glycolic acid(PLGA) nanoparticles loaded with soluble leishmanial antigen or autoclaved leishmanial antigen and explore in vitro and in vivo immunogenicity of antigen encapsulated nanoparticles. Methods: Water/oil/water double emulsion technique was employed to synthesize PLGA nanoparticles, and scanning electron microscopy, Fourier transform infrared spectroscopy and Zeta-potential measurements were used to identify the characteristics of nanoparticles. Cytotoxicity of synthetized nanoparticles on J774 macrophage were investigated by MTT assays. To determine the in vitro immunostimulatory efficacies of nanoparticles, griess reaction and ELISA was used to measure the amounts of NO and cytokines. During the in vivo analysis, Balb/c mice were immunized with vaccine formulations, and protective properties of nanoparticles were measured by Leishman Donovan unit in the liver following the infection. Cytokine levels in spleens of mice were determined by ELISA. Results: MTT assay showed that neither soluble leishmanial antigen nor autoclaved leishmanial antigen encapsulated nanoparticles showed cytotoxicity against J774 macrophage cells. Contrary to free antigens, both autoclaved leishmanial antigen-nanoparticle and soluble leishmanial antigen-nanoparticle formulations led to a 10 and 16-fold increase in NO amounts by macrophages, respectively. Leishman Donovan unit calculations revealed that soluble leishmanial antigen-nanoparticles and autoclaved leishmanial antigen-nanoparticles yielded 52% and 64% protection against visceral leishmaniasis in mouse models. Besides, in vitro and in vivo tests demonstrated that by increasing IFN-γ and IL-12 levels and inhibiting IL-4 and IL-10 secretions, autoclaved leishmanial antigen-nanoparticles and soluble leishmanial antigennanoparticles triggered Th1 immune response. Conclusions: Both autoclaved leishmanial antigen-nanoparticles and soluble leishmanial antigen-nanoparticles formulations provide exceptional in vitro and in vivo immunostimulatory activities. Hence, PLGA-based antigen delivery systems are recommended as potential vaccine candidates against visceral leishmaniasis.展开更多
The effect of Argon ion irradiation to the surface properties of poly(lactic-co-glycolic) acid (PLGA) was studied. A beam of 170 keV Argon ions was implanted at different fluencies (1 × 1012, 1 × 1013, 1 ...The effect of Argon ion irradiation to the surface properties of poly(lactic-co-glycolic) acid (PLGA) was studied. A beam of 170 keV Argon ions was implanted at different fluencies (1 × 1012, 1 × 1013, 1 × 1014, and 1 × 1015 ions/cm2). X-ray photoelectron spectroscopy (XPS) was used to analyze the evolution of the bonding microstructure of PLGA due to irradiation. Surface morphology was monitored using atomic force microscopy (AFM). AFM analysis shows that film roughness increased to maximum at the dose of 1 × 1014 ions/cm2 where the formations of hillocks were also detected. Hydrophilicity of PLGA is important for their applications in biomedicine such as bioscaffolds. Hydrophilicity was monitored using water contact angle measurements for both unmodified and ion-modified PLGA. It was observed that hydrophilicity of PLGA changes with the ion irradiation. This demonstrates that ion irradiation can be an alternative approach to control hydrophilicity of PLGA. PLGA scaffolds modified with ion irradiation could therefore be more suitable for the biomedical applications.展开更多
The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used ...The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) to prepare the NPs by adjusting the double emulsion technique using poly(vinylalcohol) as a surface active agent. The PLGA NPs were characterized for particle size and shape, controlled release of cisplatin, and degradation. Cisplatin solubility in deionized water was increased up to 4 mg/mL by simply changing the solution parameters. Cisplatin encapsulated NPs were incubated in phosphate buffered saline (PBS) at 37?C to study the release kinetics of cisplatin. Cisplatin was released in a sustained manner with less than 20% release during a 3-day period followed by 50% release during a 21-day period. A degradation study of PLGA NPs demonstrated the loss of spherical shape during a 21-day period. We also examined the cisplatin sensitive A2780 cell apoptosis when cells were incubated with cisplatin encapsulated PLGA NPs. A large number of cell apoptosis occurred as a result of cisplatin release from the PLGA NPs. These results suggest that cisplatin encapsulated PLGA NPs can be used to treat the cancer cells by injecting them into a localized site minimizing the side effects.展开更多
BACKGROUND： Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous funct...BACKGROUND： Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE： To compare the therapeutic effects of poly lactic-co-glycolic acid （PLGA）-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008. MATERIALS： Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University. METHODS： A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups （n=12）： model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μ L normal saline solution, 50 μL normal saline solution containing 50μL g Nogo A antibody, and 50 μL normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES： The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan （BBB） locomotor rating scale. RESULTS： Four weeks after injury, expression of Nogo A in microsphere group was significantly less than model and Nogo A antibody alone groups （P 〈 0.05）; while there was no significant difference between model and Nogo A antibody alone groups （P 〉 0.05）. Ten weeks after injury, microsphere group showed a significantly greater expression of neurofilament 200 than model and Nogo A antibody alone groups （P 〈 0.05）; while no significant difference was found between model and Nogo A antibody alone groups （P 〉 0.05）. At postoperative weeks 5 and 6, the score of BBB locomotor rating scale in microsphere group was significantly greater than the model group （P 〈 0.05）, and at postoperative weeks 7 10, the score was much greater than model and Nogo A antibody alone groups （P 〈 0.05）. CONCLUSION： Nogo A antibody delayed-release microspheres decreased Nogo A expression, increased neurofilament 200 expression in the injured spinal cord of rats, and promoted recovery of motor function through sustained drug release over a long-term period.展开更多
Implant-associated infection remains a difficult medical problem in orthopedic surgery. Therefore, the development of multifunctional bone implants for treating infection and regenerating lost bone tissue, which may b...Implant-associated infection remains a difficult medical problem in orthopedic surgery. Therefore, the development of multifunctional bone implants for treating infection and regenerating lost bone tissue, which may be a result of infection, is important. In the present study, we report the fabrication of enoxacin- loaded poly （lactic-co-glycolic acid） （PLGA） coating on porous magnesium scaffold （Enox-PLGA-Mg） which combine the favorable properties of magnesium, the antibacterial property and the effect of inhibition of osteoclastic bone resorption of enoxacin. The drug loaded PLGA coating of Mg scaffold enables higher drug loading efficiency （52%-56%） than non-coating enoxacin loaded Mg scaffold （Enox-Mg） （4%-5%）. Enox- PLGA-Mg exhibits sustained drug release for more than 14 days, and this controlled release of enoxacin signifcantly inhibits bacterial adhesion and prevented biofilm formation by Staphylococcus epidermidis （ATCC35984） and Staphylococcus aureus （ATCC25923）. Biocompatibility tests with Balb/c mouse embryo fibroblasts （Balb/c 3T3 cells） indicate that PLGA-Mg has better biocompatibility than Mg. Finally, we also demonstrate that Enox-PLCA-Mg extract potently inhibited osteoclast formation in vitro. Therefore, Enox- PLCA-Mg has the potential to be used as a multifunctional controlled drug delivery system bone scaffolds to prevent and/or treat orthopedic peri-implant infections.展开更多
We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-...We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application.展开更多
The aim of the present study was to develop a novel long-acting Poly(lactic-co-glycolic acid)(PLGA)-based microspheres formulation of Bisdemethoxycurcum(BDMC) by emulsionsolvent evaporation method. Meanwhile, the effe...The aim of the present study was to develop a novel long-acting Poly(lactic-co-glycolic acid)(PLGA)-based microspheres formulation of Bisdemethoxycurcum(BDMC) by emulsionsolvent evaporation method. Meanwhile, the effects of the volume ratio of the dispersed phase and continuous phase, the concentration of PLGA and PVA, the theoretical drug loading and stirring speed were investigated. The mean diameter of the microspheres was 8.5 μm and the size distribution was narrow. The encapsulation efficiency(EE) and drug loading efficiency(DLE) of BDME loaded PLGA microspheres(BDMC-PLGA-MS) was 94.18% and 8.14%,respectively. In an in vitro study of drug release, it can be concluded that the BDMC-PLGAMS exhibited sustained and long-term release properties for 96 h. Stability studies suggested that the microspheres we prepared had a very good stability. Furthermore, the results of an in vivo study indicated that the BDMC-PLGA-MS had sustained release effect and was mainly distributed in the lung tissue, and less distribution in other tissues, which indicated that microspheres could be an effective parenteral carrier for the delivery of BDMC in lung cancer treatment.展开更多
【研究目的】在提升OLI(Operational Land Imager)影像分辨率的方法中,Brovey变换在锐化图像的同时能够较好保持原多光谱图像的信息内容,对于山地、水体、植被一类地物表征非常明显,较为适合滨海地区的遥感影像处理。但Brovey变换通道...【研究目的】在提升OLI(Operational Land Imager)影像分辨率的方法中,Brovey变换在锐化图像的同时能够较好保持原多光谱图像的信息内容,对于山地、水体、植被一类地物表征非常明显,较为适合滨海地区的遥感影像处理。但Brovey变换通道限制选择三个波段进行运算,因此,如何选择并判定Brovey变换的最佳波段组合成为基于OLI影像精细划分土地利用/覆被类型的重要前提。【研究方法】本文以潍坊滨海地区为研究区,融合OLI影像波段信息量、波段间相关系数、波段组合最佳指数因子和Sheffield指数等多种方法,结合典型土地利用/覆被类型的波段特征,进行最佳波段组合识别。【研究结果】结果显示,波段754为滨海地区OLI影像数据Brovey变换融合进行土地利用/覆被类型监督分类的最佳波段组合。【结论】滨海地区OIL影像进行Brovey变换时,波段5与其它波段的相关性最小,应为必选波段;Sheffield指数、OIF指数、波段信息量、波段间相关系数结合典型土地利用/覆被类型的波段曲线特征分析是确定滨海地区的最佳波段组合的有效方法。展开更多
文摘Medical-grade synthetic poly（lactic-co-glycolic acid） polymer can be used as a biomaterial for nerve repair because of its good biocompatibility, biodegradability and adjustable degradation rate. The stress relaxation and creep properties of peripheral nerve can be greatly improved by repair with poly（lactic-co-glycolic acid） tubes. ＂Fen sciatic nerve specimens were harvested from fresh corpses within 24 hours of death, and were prepared into sciatic nerve injury models by creating a 10 mm defect in each specimen. Defects were repaired by anastomosis with nerve autografts and poly（lactic-co-glycolic acid） tubes. Stress relaxation and creep testing showed that at 7 200 seconds the sciatic nerve anastomosed by poly（lactic-co-glycolic acid） tubes exhibited a greater decrease in stress and increase in strain than those anastomosed by nerve autografts. These findings suggest that poly（lactic-co-glycolic acid） exhibits good viscoelasticity to meet the biomechanical require- ments for a biomaterial used to repair sciatic nerve injury.
基金supported by a grant from the National Key Basic Research Program of China,No.2014CB542202 and 2014CB542205the National Natural Science Foundation of China,No.30973095&81371354+2 种基金a grant from Science and Technology Project of Guangzhou,in China,No.12C32121609the Natural Science Foundation of Guangdong Province of China,No.S2013010014697 to Guo JSHong Kong SCI Fund to Wu WT
文摘In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.
基金supported by the National Natural Science Foundation of China,No.30973060
文摘Schwann cells, nerve regeneration promoters in peripheral nerve tissue engineering, can be used to repair both the peripheral and central nervous systems. However, isolation and puriifcation of Schwann cells are complicated by contamination with ifbroblasts. Current reported measures are mainly limited by either high cost or complicated procedures with low cell yields or purity. In this study, we collected dorsal root ganglia from neonatal rats from which we obtained highly puriifed Schwann cells using serum-free melanocyte culture medium. The purity of Schwann cells （〉95%） using our method was higher than that using standard medium containing fetal bovine serum. The obtained Schwann cells were implanted into poly（lactic-co-glycolic acid）/chi-tosan conduits to repair 10-mm sciatic nerve defects in rats. Results showed that axonal diameter and area were signiifcantly increased and motor functions were obviously improved in the rat sciatic nerve tissue. Experimental ifndings suggest that serum-free melanocyte culture medium is conducive to purify Schwann cells and poly（lactic-co-glycolic acid）/chitosan nerve conduits combined with Schwann cells contribute to restore sciatic nerve defects.
基金funded by the Technology Development Project of Jilin Province,No.20110492
文摘Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly（lactic-co-glycolic acid） conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly（lactic-co-glycolic acid） conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly（lactic-co-glycolic acid） conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly（lactic-co-glycolic acid） conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly（lactic-co-glycolic acid） conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly（lactic-co-glycolic acid） conduits exhibited good intensity, elasticity and plasticity, indicating that poly（lactic-co-glycolic acid） conduits are suitable for sciatic nerve injury repair.
文摘BACKGROUND： A degradable poly（lactic-co-glycolic acid） （PLGA） scaffold has been used to construct a degradable porous scaffold. This template can simulate the in vivo microenvironment and promote tissue formation. OBJECTIVE： To observe the histopathological changes during degeneration and regeneration of the intervertebral disc, and to analyze the effects of a PLGA scaffold on nerve fiber ingrowth into the lesion in vivo. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Orthopaedic Laboratory, Clinic Medical Research Institution, Sir Run Run Shaw Hospital, Zhejiang University, from December 2007 to July 2008. MATERIALS： PLGA （China Textile Academy）; growth-associated protein-43 （Life-span, USA）; and protein gene product 9.5 antibody （AbD, United Kingdom） were used in this study. METHODS： Three consecutive segments of the intervertebral disc of thirty-two healthy adult male New Zealand rabbits were exposed, comprising L3-4, L4-5 and L5-6. Experimental intervertebral disc （L4-5 and L5-6） models were established by two different methods. In the test （trephine ＋ scaffold） group, a 5-mm deep hole was drilled into the annulus fibrosus using a 3-mm diameter trephine, and the PLGA scaffold was implanted into the hole. In the acupuncture group, the remaining experimental intervertebral disc annulus fibrosus was damaged using a 16G needle at a depth of 5 mm. The L3-4 disc served as a control. MAIN OUTCOME MEASURES： Intervertebral disc degeneration was assessed using radiography, magnetic resonance imaging, and histological examination at various time points post-surgery. Nerve fiber ingrowth into the degenerated intervertebral disc was observed using immunohistochemical staining for growth-associated protein-43 and protein gene product 9.5. RESULTS： Compared with the normal controls, the heights of the damaged intervertebral discs were decreased, and T2 signal intensity was decreased in the test and acupuncture groups 2 weeks post-surgery. Intervertebral disc degeneration was faster in the test group than in the acupuncture group. PLGA was coated with newly formed tissue, gradually degraded, and absorbed, and could induce tissue ingrowth deep into the annulus fibrosus. Results of immunohistochemical staining showed that nerve fibers were distributed in newly formed tissue in the test group, and in the superficial layer or surrounding scar tissue in the acupuncture group. CONCLUSION： A porous PLGA scaffold provides an important biological channel to induce nerve fiber ingrowth deep into the degenerated intervertebral disc.
基金supported by Scientific and Technological Research Council of Turkey(TUBITAK,Grant No.213S148)
文摘Objective: To prepare and characterize poly lactic-co-glycolic acid(PLGA) nanoparticles loaded with soluble leishmanial antigen or autoclaved leishmanial antigen and explore in vitro and in vivo immunogenicity of antigen encapsulated nanoparticles. Methods: Water/oil/water double emulsion technique was employed to synthesize PLGA nanoparticles, and scanning electron microscopy, Fourier transform infrared spectroscopy and Zeta-potential measurements were used to identify the characteristics of nanoparticles. Cytotoxicity of synthetized nanoparticles on J774 macrophage were investigated by MTT assays. To determine the in vitro immunostimulatory efficacies of nanoparticles, griess reaction and ELISA was used to measure the amounts of NO and cytokines. During the in vivo analysis, Balb/c mice were immunized with vaccine formulations, and protective properties of nanoparticles were measured by Leishman Donovan unit in the liver following the infection. Cytokine levels in spleens of mice were determined by ELISA. Results: MTT assay showed that neither soluble leishmanial antigen nor autoclaved leishmanial antigen encapsulated nanoparticles showed cytotoxicity against J774 macrophage cells. Contrary to free antigens, both autoclaved leishmanial antigen-nanoparticle and soluble leishmanial antigen-nanoparticle formulations led to a 10 and 16-fold increase in NO amounts by macrophages, respectively. Leishman Donovan unit calculations revealed that soluble leishmanial antigen-nanoparticles and autoclaved leishmanial antigen-nanoparticles yielded 52% and 64% protection against visceral leishmaniasis in mouse models. Besides, in vitro and in vivo tests demonstrated that by increasing IFN-γ and IL-12 levels and inhibiting IL-4 and IL-10 secretions, autoclaved leishmanial antigen-nanoparticles and soluble leishmanial antigennanoparticles triggered Th1 immune response. Conclusions: Both autoclaved leishmanial antigen-nanoparticles and soluble leishmanial antigen-nanoparticles formulations provide exceptional in vitro and in vivo immunostimulatory activities. Hence, PLGA-based antigen delivery systems are recommended as potential vaccine candidates against visceral leishmaniasis.
文摘The effect of Argon ion irradiation to the surface properties of poly(lactic-co-glycolic) acid (PLGA) was studied. A beam of 170 keV Argon ions was implanted at different fluencies (1 × 1012, 1 × 1013, 1 × 1014, and 1 × 1015 ions/cm2). X-ray photoelectron spectroscopy (XPS) was used to analyze the evolution of the bonding microstructure of PLGA due to irradiation. Surface morphology was monitored using atomic force microscopy (AFM). AFM analysis shows that film roughness increased to maximum at the dose of 1 × 1014 ions/cm2 where the formations of hillocks were also detected. Hydrophilicity of PLGA is important for their applications in biomedicine such as bioscaffolds. Hydrophilicity was monitored using water contact angle measurements for both unmodified and ion-modified PLGA. It was observed that hydrophilicity of PLGA changes with the ion irradiation. This demonstrates that ion irradiation can be an alternative approach to control hydrophilicity of PLGA. PLGA scaffolds modified with ion irradiation could therefore be more suitable for the biomedical applications.
文摘The goal of the present study is to utilize cis-diamminedichloroplatinum (cisplatin) loaded polymer nanoparticles (NPs) to give a controlled, extended, and local drug therapy for the treatment of cancer. We have used biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) to prepare the NPs by adjusting the double emulsion technique using poly(vinylalcohol) as a surface active agent. The PLGA NPs were characterized for particle size and shape, controlled release of cisplatin, and degradation. Cisplatin solubility in deionized water was increased up to 4 mg/mL by simply changing the solution parameters. Cisplatin encapsulated NPs were incubated in phosphate buffered saline (PBS) at 37?C to study the release kinetics of cisplatin. Cisplatin was released in a sustained manner with less than 20% release during a 3-day period followed by 50% release during a 21-day period. A degradation study of PLGA NPs demonstrated the loss of spherical shape during a 21-day period. We also examined the cisplatin sensitive A2780 cell apoptosis when cells were incubated with cisplatin encapsulated PLGA NPs. A large number of cell apoptosis occurred as a result of cisplatin release from the PLGA NPs. These results suggest that cisplatin encapsulated PLGA NPs can be used to treat the cancer cells by injecting them into a localized site minimizing the side effects.
基金the National Natural Science Foundation of China,No.30471759
文摘BACKGROUND： Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE： To compare the therapeutic effects of poly lactic-co-glycolic acid （PLGA）-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord. DESIGN, TIME AND SETTING： A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008. MATERIALS： Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University. METHODS： A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups （n=12）： model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μ L normal saline solution, 50 μL normal saline solution containing 50μL g Nogo A antibody, and 50 μL normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES： The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan （BBB） locomotor rating scale. RESULTS： Four weeks after injury, expression of Nogo A in microsphere group was significantly less than model and Nogo A antibody alone groups （P 〈 0.05）; while there was no significant difference between model and Nogo A antibody alone groups （P 〉 0.05）. Ten weeks after injury, microsphere group showed a significantly greater expression of neurofilament 200 than model and Nogo A antibody alone groups （P 〈 0.05）; while no significant difference was found between model and Nogo A antibody alone groups （P 〉 0.05）. At postoperative weeks 5 and 6, the score of BBB locomotor rating scale in microsphere group was significantly greater than the model group （P 〈 0.05）, and at postoperative weeks 7 10, the score was much greater than model and Nogo A antibody alone groups （P 〈 0.05）. CONCLUSION： Nogo A antibody delayed-release microspheres decreased Nogo A expression, increased neurofilament 200 expression in the injured spinal cord of rats, and promoted recovery of motor function through sustained drug release over a long-term period.
基金supported by the Key National Basic Research Program of China (Grant No. 2012CB619101)the National Natural Science Foundation of China (No. 81190133)+3 种基金the National Natural Science Foundation for the Youth of China (Grant Nos. 81401852 and 31500777)the Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine (No. BXJ201430)the Natural Science Foundation of Shanghai (No. 14ZR1424000)"Chen Guang" Project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 14CG14)
文摘Implant-associated infection remains a difficult medical problem in orthopedic surgery. Therefore, the development of multifunctional bone implants for treating infection and regenerating lost bone tissue, which may be a result of infection, is important. In the present study, we report the fabrication of enoxacin- loaded poly （lactic-co-glycolic acid） （PLGA） coating on porous magnesium scaffold （Enox-PLGA-Mg） which combine the favorable properties of magnesium, the antibacterial property and the effect of inhibition of osteoclastic bone resorption of enoxacin. The drug loaded PLGA coating of Mg scaffold enables higher drug loading efficiency （52%-56%） than non-coating enoxacin loaded Mg scaffold （Enox-Mg） （4%-5%）. Enox- PLGA-Mg exhibits sustained drug release for more than 14 days, and this controlled release of enoxacin signifcantly inhibits bacterial adhesion and prevented biofilm formation by Staphylococcus epidermidis （ATCC35984） and Staphylococcus aureus （ATCC25923）. Biocompatibility tests with Balb/c mouse embryo fibroblasts （Balb/c 3T3 cells） indicate that PLGA-Mg has better biocompatibility than Mg. Finally, we also demonstrate that Enox-PLCA-Mg extract potently inhibited osteoclast formation in vitro. Therefore, Enox- PLCA-Mg has the potential to be used as a multifunctional controlled drug delivery system bone scaffolds to prevent and/or treat orthopedic peri-implant infections.
基金supported by the National Natural Science Foundation of China,No.81371687,81171457
文摘We have designed a novel nerve guidance conduit（NGC） made from silk fibroin and poly（lactic-co-glycolic acid） through electrospinning and weaving（ESP-NGCs）. Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application.
文摘The aim of the present study was to develop a novel long-acting Poly(lactic-co-glycolic acid)(PLGA)-based microspheres formulation of Bisdemethoxycurcum(BDMC) by emulsionsolvent evaporation method. Meanwhile, the effects of the volume ratio of the dispersed phase and continuous phase, the concentration of PLGA and PVA, the theoretical drug loading and stirring speed were investigated. The mean diameter of the microspheres was 8.5 μm and the size distribution was narrow. The encapsulation efficiency(EE) and drug loading efficiency(DLE) of BDME loaded PLGA microspheres(BDMC-PLGA-MS) was 94.18% and 8.14%,respectively. In an in vitro study of drug release, it can be concluded that the BDMC-PLGAMS exhibited sustained and long-term release properties for 96 h. Stability studies suggested that the microspheres we prepared had a very good stability. Furthermore, the results of an in vivo study indicated that the BDMC-PLGA-MS had sustained release effect and was mainly distributed in the lung tissue, and less distribution in other tissues, which indicated that microspheres could be an effective parenteral carrier for the delivery of BDMC in lung cancer treatment.
文摘【研究目的】在提升OLI(Operational Land Imager)影像分辨率的方法中,Brovey变换在锐化图像的同时能够较好保持原多光谱图像的信息内容,对于山地、水体、植被一类地物表征非常明显,较为适合滨海地区的遥感影像处理。但Brovey变换通道限制选择三个波段进行运算,因此,如何选择并判定Brovey变换的最佳波段组合成为基于OLI影像精细划分土地利用/覆被类型的重要前提。【研究方法】本文以潍坊滨海地区为研究区,融合OLI影像波段信息量、波段间相关系数、波段组合最佳指数因子和Sheffield指数等多种方法,结合典型土地利用/覆被类型的波段特征,进行最佳波段组合识别。【研究结果】结果显示,波段754为滨海地区OLI影像数据Brovey变换融合进行土地利用/覆被类型监督分类的最佳波段组合。【结论】滨海地区OIL影像进行Brovey变换时,波段5与其它波段的相关性最小,应为必选波段;Sheffield指数、OIF指数、波段信息量、波段间相关系数结合典型土地利用/覆被类型的波段曲线特征分析是确定滨海地区的最佳波段组合的有效方法。
