Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Holl...Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3.展开更多
Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in ra...Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa- line groups than in the nerve growth factor-microspheres and autologous nerve groups. Electro- physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di- ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits com- bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits.展开更多
Chitosan, the N\|deacetylated form of chitin, has good biocompatibility and biodegradability. This paper investigates the feasibility of using chitosan conduits for peripheral nerve regeneration. Cell culture experime...Chitosan, the N\|deacetylated form of chitin, has good biocompatibility and biodegradability. This paper investigates the feasibility of using chitosan conduits for peripheral nerve regeneration. Cell culture experiments were used to test the material's cytotoxicity and affinity to nerve cells. Conduit implantation experiments were used to study the degradation of the material and the regeneration of injured sciatic nerves. The primary results indicate that chitosan has good mechanical properties, biocompatibility, and biodegradability and it may be a promising biomaterial for peripheral nerve regeneration.展开更多
The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al.,...The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al., 2014; Zhu and Lou, 2014）. With advances in tissue engineering and biomaterials, tissue-engineered nerve conduits with various biomaterials and structures, such as collagen and chitosan nerve conduits, have already been used in the clinic as alternatives to autologous nerve in the repair of peripheral nerve injury （Wang et al., 2012; Svizenska et al., 2013; Eppenberger et al., 2014; Gu et al., 2014; Koudehi et al., 2014; MoyaDiaz et al., 2014; Novajra et al., 2014; Okamoto et al., 2014; Shea et al., 2014; Singh et al., 2014; Tamaki et al., 2014; Yu et al., 2014）. Therefore, new simple and effective methods展开更多
A micro-envioment for nerve cells and tissue growth were designed and constructed via surface modification of poly（L-lactide-co-glycolide）（PLGA） with chitosan and hydroxyapatire（HA）. The poly（L_lactide-co-glyco...A micro-envioment for nerve cells and tissue growth were designed and constructed via surface modification of poly（L-lactide-co-glycolide）（PLGA） with chitosan and hydroxyapatire（HA）. The poly（L_lactide-co-glycolide）/chitosan/hydroxyapatite （PLGA/chitosan/HA） conduits were manufactured by a combined solvent casting and particulate leaching technique. The conduits were highly porous with an interconnected pore structure and 76.5% porosity. Micropores with 50-100 micrometer diameter were formed in the conduits. In vivo application of PLGA/chitosan/HA conduits for reconstruction of 10 mm sciatic nerve defect was assessed by the walking track analysis, the quantifying of the wet weight of tibialis anterior muscle and the histological assessment. The conduits in host rats in vivo can not only be an effective in promoting regenerating of nerves but can also lead to favorable nerve functional recovery.展开更多
基金funded by the Spanish “Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía y Competitividad (Instituto de Salud Carlos Ⅲ),grants Nos. FIS PI14-1343, FIS PI17-0393, and FIS PI20-0318 co-financed by the “Fondo Europeo de Desarrollo Regional ERDF-FEDER European Union”grant No. P18-RT-5059 by “Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020),Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, España”grant No. A-CTS-498-UGR18 by “Programa Operativo FEDER Andalucía 2014–2020, Universidad de Granada, Junta de Andalucía, España”, co-funded by ERDF-FEDER, the European Union (all to VC)
文摘Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3.
基金supported by the National Natural Science Foundation of China,No.30872898,81371116the Natural Science Foundation of Beijing,No.7132173
文摘Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa- line groups than in the nerve growth factor-microspheres and autologous nerve groups. Electro- physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di- ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits com- bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits.
基金the State Science and Technology Commis sion! (No.81 9 0 7 0 1 )
文摘Chitosan, the N\|deacetylated form of chitin, has good biocompatibility and biodegradability. This paper investigates the feasibility of using chitosan conduits for peripheral nerve regeneration. Cell culture experiments were used to test the material's cytotoxicity and affinity to nerve cells. Conduit implantation experiments were used to study the degradation of the material and the regeneration of injured sciatic nerves. The primary results indicate that chitosan has good mechanical properties, biocompatibility, and biodegradability and it may be a promising biomaterial for peripheral nerve regeneration.
基金supported by the National High Technology Research and Development Program of China,No.2012AA020502the National Natural Science Foundation of China,No.81171457 and 81371687the Priority of Academic Program Development of Jiangsu Higher Education Institutions
文摘The repair of peripheral nerve injuries with autologous nerve remains the gold standard （Wang et al., 2005; Yao et al., 2010; Deal et al., 2012; Kriebel et al., 2014; Liu et al., 2014; Tamaki et al., 2014; Yu et al., 2014; Zhu and Lou, 2014）. With advances in tissue engineering and biomaterials, tissue-engineered nerve conduits with various biomaterials and structures, such as collagen and chitosan nerve conduits, have already been used in the clinic as alternatives to autologous nerve in the repair of peripheral nerve injury （Wang et al., 2012; Svizenska et al., 2013; Eppenberger et al., 2014; Gu et al., 2014; Koudehi et al., 2014; MoyaDiaz et al., 2014; Novajra et al., 2014; Okamoto et al., 2014; Shea et al., 2014; Singh et al., 2014; Tamaki et al., 2014; Yu et al., 2014）. Therefore, new simple and effective methods
基金Funded by the National Natural Science Foundation of China(No.50774096)
文摘A micro-envioment for nerve cells and tissue growth were designed and constructed via surface modification of poly（L-lactide-co-glycolide）（PLGA） with chitosan and hydroxyapatire（HA）. The poly（L_lactide-co-glycolide）/chitosan/hydroxyapatite （PLGA/chitosan/HA） conduits were manufactured by a combined solvent casting and particulate leaching technique. The conduits were highly porous with an interconnected pore structure and 76.5% porosity. Micropores with 50-100 micrometer diameter were formed in the conduits. In vivo application of PLGA/chitosan/HA conduits for reconstruction of 10 mm sciatic nerve defect was assessed by the walking track analysis, the quantifying of the wet weight of tibialis anterior muscle and the histological assessment. The conduits in host rats in vivo can not only be an effective in promoting regenerating of nerves but can also lead to favorable nerve functional recovery.
