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
Three-dimensional porous poly-lactic acid(PLA) scaffold was fabricated using fused deposition modeling(FDM) method including 30%, 50% and 70% nominal porosity. Study of phases in initial polymeric material and printed...Three-dimensional porous poly-lactic acid(PLA) scaffold was fabricated using fused deposition modeling(FDM) method including 30%, 50% and 70% nominal porosity. Study of phases in initial polymeric material and printed scaffolds was done by X-ray diffraction(XRD), and no significant phase difference was observed due to the manufacturing process, and the poly-lactic acid retains its crystalline properties. The results of the mechanical properties evaluation by the compression test show that the mechanical properties of the scaffold have decreased significantly with increasing the porosity of scaffold. The microstructure of scaffolds were studied by scanning electron microscope(SEM), showing that the pores had a regular arrangement and their morphology changed with porosity change. The mechanical properties of the poly-lactic acid scaffolds printed using fused deposition modeling, can be adapted to the surrounding tissue, by porosity change.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
In this study, poly(L-lactic acid)/ammonium persulfate doped-polypyrrole composite fibrous scaffolds with moderate conductivity were produced by combining electrospinning with in situ polymerization. PC12 cells were...In this study, poly(L-lactic acid)/ammonium persulfate doped-polypyrrole composite fibrous scaffolds with moderate conductivity were produced by combining electrospinning with in situ polymerization. PC12 cells were cultured on these fibrous scaffolds and their growth following electrical stimulation (0-20.0 μA stimulus intensity, for 1-4 days) was observed using inverted light microscopy, and scanning electron microscopy coupled with the MTT cell viability test. The results demonstrated that the poly(L-lactic acid)/ammonium persulfate doped-polypyrrole fibrous scaffold was a dual multi-porous micro/nano fibrous scaffold. An electrical stimulation with a current intensity 5.0- 10.0 μAfor about 2 days enhanced neuronal growth and neurite outgrowth, while a high current intensity (over 15.0 μA) suppressed them. These results indicate that electrical stimulation with a moderate current intensity for an optimum time frame can promote neuronal growth and neurite outgrowth in an intensity- and time-dependent manner.展开更多
A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment,survival,and retention in cell transplantation processes.This study presents a composite scaffold made of poly(ε-capr...A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment,survival,and retention in cell transplantation processes.This study presents a composite scaffold made of poly(ε-caprolactone)(PCL)and methacrylated hyaluronic acid(MeHA)hydrogel and describes the corresponding physical properties(surface area,porosity,and mechanical strength)and host response(angiogenesis and fibrosis)after subcutaneous transplantation.Specifically,we synthesise MeHA with different degrees of substitution and fabricate a PCL scaffold with different porosities.Subsequently,we construct a series of PCL/MeHA composite scaffolds by combining these hydrogels and scaffolds.In experiments with mice,the scaffold composed of 3%PCL and 10-100 kDa,degree of substitution 70%MeHA results in the least fibrosis and a higher degree of angiogenesis.This study highlights the potential of PCL/MeHA composite scaffolds for subcutaneous cell transplantation,given their desirable physical properties and host response.展开更多
Background Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells (NSCs) could survive in poly...Background Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells (NSCs) could survive in poly(L-lactic-co-glycolic acid) (PLGA) scaffolds and, when cografted with Schwann cells (SCs), could be induced to differentiate towards neurons which form synaptic connection and eventually facilitate axonal regeneration and myelination and motor function. Methods NSCs and SCs which were seeded within the directional PLGA scaffolds were implanted in hemisected adult rat spinal cord. Control rats were similarly injured and implanted of scaffolds with or without NSCs. Survival, migration, differentiation, synaptic formation of NSCs, axonal regeneration and myelination and motor function were analyzed. Student's t test was used to determine differences in surviving percentage of NSCs. One-way analysis of variance (ANOVA) was used to determine the differences in the number of axons myelinated in the scaffolds, the mean latency and amplitude of cortical motor evoked potentials (CMEPs) and Basso, Beattie & Bresnahan locomotor rating scale (BBB) score. The X2 test was used to determine the differences in recovery percentage of CMEPs. Results NSCs survived, but the majority migrated into adjacent host cord and died mostly. Survival rate of NSCs with SCs was higher than that of NSCs without SCs ((1.7831±0.0402)% vs. (1.4911±0.0313)%, P 〈0.001). Cografted with SCs, NSCs were induced to differentiate towards neurons and might form synaptic connection. The mean number of myelinated axons in PLGA+NSCs+SCs group was more than that in PLGA+NSCs group and in PLGA group ((110.25±30.46) vs. (18.25±3.30) and (11.25±5.54), P 〈0.01). The percentage of CMEPs recovery in PLGA+NSCs+SCs group was higher than in the other groups (84.8% vs, 50.0% and 37.5%, P 〈0.05). The amplitude of CMEPs in PLGA+NSCs+SCs group was higher than in the other groups ((1452.63±331.70) IJV vs. (428.84±193.01) IJV and (117.33±14.40) μV, P 〈0.05). Ipsilateral retransection resulted in disappearance again and functional loss of CMEPs for a few days. But contralateral retransection completely damaged the bilateral motor function. Conclusions NSCs can survive in PLGA scaffolds, and SCs promote NSCs to survive and differentiate towards neurons in vivo which even might form synaptic connection. The scaffolds seeded with cells facilitate axonal regeneration and myelination and motor function recovery. But regenerating axons have limited contribution to motor function recovery.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
Soft tissues are important for aesthetic considerations in implant therapy. The purpose of this study was to investigate soft tissue augmentation by using porous poly-DL-lactic acid (PDLLA)shaped as a tablet, with a d...Soft tissues are important for aesthetic considerations in implant therapy. The purpose of this study was to investigate soft tissue augmentation by using porous poly-DL-lactic acid (PDLLA)shaped as a tablet, with a diameter of5.0 mmand a height of2.0 mm. Porous PDLLA was implanted between the periosteal and epithelial tissues in 25 rats that were sacrificed at 1, 2, 4, 12, and 24 weeks. The average height of the PDLLA scaffolds at approximately 24 weeks was 1.85 ±0.08 mm, and the molecular weight decreased with time. Sinusoidal capillaries at 1 week, connective tissues at 4 weeks, and necrotic tissues at 24 weeks were observed more than other periods. At 24 weeks, the connective tissue surviving in the pores was confirmed to contain blood vessels;therefore, blood vessels are considered to be critical for the survival of soft tissue in scaffold pores. In this study, PDLLA was found to be useful for soft tissue augmentation in the long term. Although the molecular weight of PDLLA decreased with time, the height of the PDLLA scaffolds was preserved. The connective tissue surviving in the pores of the scaffolds at 24 weeks were associated with blood vessels. Further studies are necessary to investigate the optimal scaffold shape and surface characteristics to improve the penetration of blood vessels.展开更多
Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor (NgR)-silenced neural stem cells and Schwann cells may be able to ...Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor (NgR)-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly(D,L-lactide-co-glycolic acid) (PLGA) scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells + PLGA group, hindlimb motor function and nerve electrophysiological function were dearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold + mild hypothermia at 34℃ for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.展开更多
Tissue engineering scaffolds require a controlled pore size and interconnected pore structures to support the host tissue growth. In the present study, three dimensional (3D) hybrid scaffolds of poly lactic acid (...Tissue engineering scaffolds require a controlled pore size and interconnected pore structures to support the host tissue growth. In the present study, three dimensional (3D) hybrid scaffolds of poly lactic acid (PLA) and poly glycolic acid (PGA) were fabricated using solvent casting/particulate leaching. In this case, partially fused NaCl particles were used as porogen (200-300μ) to improve the overall porosity (≥90%) and internal texture of scaffolds. Differential scanning calorimeter (DSC) analysis of these porous scaffolds revealed a gradual reduction in glass transition temperature (Tg) (from 48°C to 42.5°C) with increase in hydrophilic PGA content. The potential applications of these scaffolds as implants were further tested for their biocompatibility and biodegradability in four simulated body fluid (SBF) types in vitro. Whereas, simulated body fluid (SBF) Type1 with the optimal amount of HCO 3 ions was found to be more appropriate and sensible for testing the bioactivity of scaffolds. Among three combinations of polymer scaffolds, sample B with a ratio of 75:25 of PLA: PGA showed greater stability in body fluids (pH 7.2) with an optimum degradation rate (9% to 12% approx). X-ray diffractogram also confirmed a thin layer of hydroxyapatite deposition over sample B with all SBF types in vitro.展开更多
A degradable poly(lactic-co-glycolic acid, LA:GA=80:20)(PLGA) urethral tubular scaffold was fabricated by electrospinning. In order to enhance the mechanical properties, the scaffold was crosslinked with glutara...A degradable poly(lactic-co-glycolic acid, LA:GA=80:20)(PLGA) urethral tubular scaffold was fabricated by electrospinning. In order to enhance the mechanical properties, the scaffold was crosslinked with glutaraldehyde. The structure and properties of the crosslinked scaffolds were investigated by the mechanical property testing, scanning electron microscopy(SEM), degradability test in vitro and 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-diphenytetrazo- liumromide(MTT). The results show that the scaffold has the nano-structure. The pore size and the porosity are suitable for cell seeding, growth and extracellular matrix production. Although influenced by the crosslinking slightly, the pore size and the porosity could still support cell proliferation and tissuse formation. The mechanical properties are remarkably increased by the crosslinking of glutaraldehyde, and it could meet the demands of a urethral stent. The scaffold could completely collapse within 70 d. The results of the biocompatibility test show that the PLGA scaffold had no cytotoxicity.展开更多
The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/...The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.展开更多
In this study,mesoporous bioactive glass particles(MBGs) are incorporated into poly(lactic-co-glycolic acid)(PLGA) to fabricate highly interconnected macroporous composite scaffolds with enhanced mechanical and biolog...In this study,mesoporous bioactive glass particles(MBGs) are incorporated into poly(lactic-co-glycolic acid)(PLGA) to fabricate highly interconnected macroporous composite scaffolds with enhanced mechanical and biological properties via a developed supercritical carbon dioxide(scCO_(2)) foaming method Scaffolds show favorable highly interconnected and macroporous structure through a high foaming pressure and long venting time foaming strategy.Specifically,scaffolds with porosity from 73% to 85%,pore size from 120 μm to 320 μm and interconnectivity of over 95% are controllably fabricated at MBG content from 0 wt% to 20 wt%.In comparison with neat PLGA scaffolds,composite scaffolds perform improved strength(up to 1.5 folds) and Young's modulus(up to 3 folds).The interconnected macroporous structure is beneficial to the ingrowth of cells.More importantly,composite scaffolds also provide a more promising microenvironment for cellular proliferation and adhesion with the release of bioactive ions.Hopefully,MBG/PLGA scaffolds developed by the green foaming strategy in this work show promising morphological,mechanical and biological features for tissue regeneration.展开更多
Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits...Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.展开更多
A new entire biodegradable scaffold has been developed which does not require precellularization before transplantation.This new kind of vascular scaffold prototype made from porous poly-ε-caprolactone( PCL) membrane...A new entire biodegradable scaffold has been developed which does not require precellularization before transplantation.This new kind of vascular scaffold prototype made from porous poly-ε-caprolactone( PCL) membrane to provide three-dimensional environment for cell growth, and embedded with weft-knitted polylactic acid( PLA) fabric to support mechanics.The aim of this paper is to study the variation tendency of mechanical properties with the fabric spacing changing.The basic geometrical parameters were measured to characterize properties of the samples.The tensile and compressive elastic recovery of the samples were tested by the universal mechanical tester and radial compression apparatus,respectively.Both tensile and compressive properties enhanced when reducing the fabric spacing of the composite vascular scaffold.展开更多
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.
文摘Three-dimensional porous poly-lactic acid(PLA) scaffold was fabricated using fused deposition modeling(FDM) method including 30%, 50% and 70% nominal porosity. Study of phases in initial polymeric material and printed scaffolds was done by X-ray diffraction(XRD), and no significant phase difference was observed due to the manufacturing process, and the poly-lactic acid retains its crystalline properties. The results of the mechanical properties evaluation by the compression test show that the mechanical properties of the scaffold have decreased significantly with increasing the porosity of scaffold. The microstructure of scaffolds were studied by scanning electron microscope(SEM), showing that the pores had a regular arrangement and their morphology changed with porosity change. The mechanical properties of the poly-lactic acid scaffolds printed using fused deposition modeling, can be adapted to the surrounding tissue, by porosity change.
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 the National Natural Science Foundation of China,No.51073072the Natural Science Foundation of Zhejiang Province in China,No.Y4100745+1 种基金the Key Laboratory Open Foundation of Advanced Textile Materials&Manufacturing Technology of Zhejiang Sci-Tech University from Ministry of Education of China,No.2009007the Science and Technology Commission of Jiaxing Municipality Program,No.2010AY1089
文摘In this study, poly(L-lactic acid)/ammonium persulfate doped-polypyrrole composite fibrous scaffolds with moderate conductivity were produced by combining electrospinning with in situ polymerization. PC12 cells were cultured on these fibrous scaffolds and their growth following electrical stimulation (0-20.0 μA stimulus intensity, for 1-4 days) was observed using inverted light microscopy, and scanning electron microscopy coupled with the MTT cell viability test. The results demonstrated that the poly(L-lactic acid)/ammonium persulfate doped-polypyrrole fibrous scaffold was a dual multi-porous micro/nano fibrous scaffold. An electrical stimulation with a current intensity 5.0- 10.0 μAfor about 2 days enhanced neuronal growth and neurite outgrowth, while a high current intensity (over 15.0 μA) suppressed them. These results indicate that electrical stimulation with a moderate current intensity for an optimum time frame can promote neuronal growth and neurite outgrowth in an intensity- and time-dependent manner.
基金supported by Collaborative Research Fund from the Research Grants Council(RGC)of the Hong Kong Special Administrative Region China,No.C5044-21GResearch Institute of Tsinghua at Pearl River Delta,No.9239094(both to CX).
文摘A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment,survival,and retention in cell transplantation processes.This study presents a composite scaffold made of poly(ε-caprolactone)(PCL)and methacrylated hyaluronic acid(MeHA)hydrogel and describes the corresponding physical properties(surface area,porosity,and mechanical strength)and host response(angiogenesis and fibrosis)after subcutaneous transplantation.Specifically,we synthesise MeHA with different degrees of substitution and fabricate a PCL scaffold with different porosities.Subsequently,we construct a series of PCL/MeHA composite scaffolds by combining these hydrogels and scaffolds.In experiments with mice,the scaffold composed of 3%PCL and 10-100 kDa,degree of substitution 70%MeHA results in the least fibrosis and a higher degree of angiogenesis.This study highlights the potential of PCL/MeHA composite scaffolds for subcutaneous cell transplantation,given their desirable physical properties and host response.
基金This work was supported by the grant from the International Cooperation Research Foundation of National Natural Science Foundation of China (No. 30540450581). Conflict of interest: none.
文摘Background Various tissue engineering strategies have been developed to facilitate axonal regeneration after spinal cord injury. This study aimed to investigate whether neural stem cells (NSCs) could survive in poly(L-lactic-co-glycolic acid) (PLGA) scaffolds and, when cografted with Schwann cells (SCs), could be induced to differentiate towards neurons which form synaptic connection and eventually facilitate axonal regeneration and myelination and motor function. Methods NSCs and SCs which were seeded within the directional PLGA scaffolds were implanted in hemisected adult rat spinal cord. Control rats were similarly injured and implanted of scaffolds with or without NSCs. Survival, migration, differentiation, synaptic formation of NSCs, axonal regeneration and myelination and motor function were analyzed. Student's t test was used to determine differences in surviving percentage of NSCs. One-way analysis of variance (ANOVA) was used to determine the differences in the number of axons myelinated in the scaffolds, the mean latency and amplitude of cortical motor evoked potentials (CMEPs) and Basso, Beattie & Bresnahan locomotor rating scale (BBB) score. The X2 test was used to determine the differences in recovery percentage of CMEPs. Results NSCs survived, but the majority migrated into adjacent host cord and died mostly. Survival rate of NSCs with SCs was higher than that of NSCs without SCs ((1.7831±0.0402)% vs. (1.4911±0.0313)%, P 〈0.001). Cografted with SCs, NSCs were induced to differentiate towards neurons and might form synaptic connection. The mean number of myelinated axons in PLGA+NSCs+SCs group was more than that in PLGA+NSCs group and in PLGA group ((110.25±30.46) vs. (18.25±3.30) and (11.25±5.54), P 〈0.01). The percentage of CMEPs recovery in PLGA+NSCs+SCs group was higher than in the other groups (84.8% vs, 50.0% and 37.5%, P 〈0.05). The amplitude of CMEPs in PLGA+NSCs+SCs group was higher than in the other groups ((1452.63±331.70) IJV vs. (428.84±193.01) IJV and (117.33±14.40) μV, P 〈0.05). Ipsilateral retransection resulted in disappearance again and functional loss of CMEPs for a few days. But contralateral retransection completely damaged the bilateral motor function. Conclusions NSCs can survive in PLGA scaffolds, and SCs promote NSCs to survive and differentiate towards neurons in vivo which even might form synaptic connection. The scaffolds seeded with cells facilitate axonal regeneration and myelination and motor function recovery. But regenerating axons have limited contribution to motor function recovery.
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Soft tissues are important for aesthetic considerations in implant therapy. The purpose of this study was to investigate soft tissue augmentation by using porous poly-DL-lactic acid (PDLLA)shaped as a tablet, with a diameter of5.0 mmand a height of2.0 mm. Porous PDLLA was implanted between the periosteal and epithelial tissues in 25 rats that were sacrificed at 1, 2, 4, 12, and 24 weeks. The average height of the PDLLA scaffolds at approximately 24 weeks was 1.85 ±0.08 mm, and the molecular weight decreased with time. Sinusoidal capillaries at 1 week, connective tissues at 4 weeks, and necrotic tissues at 24 weeks were observed more than other periods. At 24 weeks, the connective tissue surviving in the pores was confirmed to contain blood vessels;therefore, blood vessels are considered to be critical for the survival of soft tissue in scaffold pores. In this study, PDLLA was found to be useful for soft tissue augmentation in the long term. Although the molecular weight of PDLLA decreased with time, the height of the PDLLA scaffolds was preserved. The connective tissue surviving in the pores of the scaffolds at 24 weeks were associated with blood vessels. Further studies are necessary to investigate the optimal scaffold shape and surface characteristics to improve the penetration of blood vessels.
基金supported by a grant from the Application Basis and Front Technology Projects of Tianjin(Science and Technology Foundation of Tianjin),No.12JCYBJC18000
文摘Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor (NgR)-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly(D,L-lactide-co-glycolic acid) (PLGA) scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells + PLGA group, hindlimb motor function and nerve electrophysiological function were dearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold + mild hypothermia at 34℃ for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury.
文摘Tissue engineering scaffolds require a controlled pore size and interconnected pore structures to support the host tissue growth. In the present study, three dimensional (3D) hybrid scaffolds of poly lactic acid (PLA) and poly glycolic acid (PGA) were fabricated using solvent casting/particulate leaching. In this case, partially fused NaCl particles were used as porogen (200-300μ) to improve the overall porosity (≥90%) and internal texture of scaffolds. Differential scanning calorimeter (DSC) analysis of these porous scaffolds revealed a gradual reduction in glass transition temperature (Tg) (from 48°C to 42.5°C) with increase in hydrophilic PGA content. The potential applications of these scaffolds as implants were further tested for their biocompatibility and biodegradability in four simulated body fluid (SBF) types in vitro. Whereas, simulated body fluid (SBF) Type1 with the optimal amount of HCO 3 ions was found to be more appropriate and sensible for testing the bioactivity of scaffolds. Among three combinations of polymer scaffolds, sample B with a ratio of 75:25 of PLA: PGA showed greater stability in body fluids (pH 7.2) with an optimum degradation rate (9% to 12% approx). X-ray diffractogram also confirmed a thin layer of hydroxyapatite deposition over sample B with all SBF types in vitro.
基金Supported by the National Natural Science Foundation of China(No. 50973043)
文摘A degradable poly(lactic-co-glycolic acid, LA:GA=80:20)(PLGA) urethral tubular scaffold was fabricated by electrospinning. In order to enhance the mechanical properties, the scaffold was crosslinked with glutaraldehyde. The structure and properties of the crosslinked scaffolds were investigated by the mechanical property testing, scanning electron microscopy(SEM), degradability test in vitro and 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-diphenytetrazo- liumromide(MTT). The results show that the scaffold has the nano-structure. The pore size and the porosity are suitable for cell seeding, growth and extracellular matrix production. Although influenced by the crosslinking slightly, the pore size and the porosity could still support cell proliferation and tissuse formation. The mechanical properties are remarkably increased by the crosslinking of glutaraldehyde, and it could meet the demands of a urethral stent. The scaffold could completely collapse within 70 d. The results of the biocompatibility test show that the PLGA scaffold had no cytotoxicity.
基金National Natural Science Foundations of China(Nos.31271028,31570984)Innovation Program of Shanghai Municipal Education Commission,China(No.13ZZ051)+2 种基金International Cooperation Fund of the Science and Technology Commission of Shanghai Municipality,China(No.15540723400)Open Foundation of State Key Laboratory for Modification of Chemical Fibers and Polymer Materials,China(No.LK1416)“111 Project” Biomedical Textile Materials Science and Technology,China(No.B07024)
文摘The combination of micro-carriers and polymer scaffolds as promising bone grafts have attracted considerable interest in recent decades.The poly(L-lactic acid)/poly(lactic-co-glycolic acid)/polycaprolactone(PLLA/PLGA/PCL)composite scaffold with porous structure was fabricated by thermally induced phase separation(TIPS).Dexamethasone(DEX)was incorporated into PLGA microspheres and then loaded on the PLLA/PLGA/PCL scaffoldtopreparethedesiredcompositescaffold.The physicochemical properties of the prepared composite scaffold were characterized.The morphology of rat bone marrow mesenchymal stem cells(BMSCs)grown on scaffolds was observed using scanning electron microscope(SEM)and fluorescence microscope.The resultsshowedthatthePLLA/PLGA/PCLscaffoldhad interconnected macropores and biomimetic nanofibrous structure.In addition,DEX can be released from scaffold in a sustained manner.More importantly,DEX loaded composite scaffold can effectively support the proliferation of BMSCs as indicated by fluorescence observation and cell proliferation assay.The results suggested that the prepared PLLA/PLGA/PCL composite scaffold incorporating drug-loaded PLGA microspheres could hold great potential for bone tissue engineering applications.
基金the National Natural Science Foundation of China (Grant No. 21676083)the Fundamental Research Funds for the Central Universities111 Project (Grant No. B20031)。
文摘In this study,mesoporous bioactive glass particles(MBGs) are incorporated into poly(lactic-co-glycolic acid)(PLGA) to fabricate highly interconnected macroporous composite scaffolds with enhanced mechanical and biological properties via a developed supercritical carbon dioxide(scCO_(2)) foaming method Scaffolds show favorable highly interconnected and macroporous structure through a high foaming pressure and long venting time foaming strategy.Specifically,scaffolds with porosity from 73% to 85%,pore size from 120 μm to 320 μm and interconnectivity of over 95% are controllably fabricated at MBG content from 0 wt% to 20 wt%.In comparison with neat PLGA scaffolds,composite scaffolds perform improved strength(up to 1.5 folds) and Young's modulus(up to 3 folds).The interconnected macroporous structure is beneficial to the ingrowth of cells.More importantly,composite scaffolds also provide a more promising microenvironment for cellular proliferation and adhesion with the release of bioactive ions.Hopefully,MBG/PLGA scaffolds developed by the green foaming strategy in this work show promising morphological,mechanical and biological features for tissue regeneration.
文摘Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.
基金the Fundamental Research Funds for the Central Universities,China,National Natural Science Foundation of China,"111 Project" Biomedical Textile Materials Science and Technology,China,the Donghua University Innovation Fund of Graduate Project,China
文摘A new entire biodegradable scaffold has been developed which does not require precellularization before transplantation.This new kind of vascular scaffold prototype made from porous poly-ε-caprolactone( PCL) membrane to provide three-dimensional environment for cell growth, and embedded with weft-knitted polylactic acid( PLA) fabric to support mechanics.The aim of this paper is to study the variation tendency of mechanical properties with the fabric spacing changing.The basic geometrical parameters were measured to characterize properties of the samples.The tensile and compressive elastic recovery of the samples were tested by the universal mechanical tester and radial compression apparatus,respectively.Both tensile and compressive properties enhanced when reducing the fabric spacing of the composite vascular scaffold.