| Title | Aligned chitosan nanofiber hydrogel grafted with peptides mimicking bioactive brain-derived neurotrophic factor and vascular endothelial growth factor repair long-distance sciatic nerve defects in rats |
| Authors | Rao, Feng Wang, Yanhua Zhang, Dianying Lu, Changfeng Cao, Zheng Sui, Jiajie Wu, Mengjiao Zhang, Yawen Pi, Wei Wang, Bo Kou, Yuhui Wang, Xiumei Zhang, Peixun Jiang, Baoguo |
| Affiliation | Peking Univ, Dept Orthoped & Trauma, Peoples Hosp, Beijing 100044, Peoples R China Tsinghua Univ, Sch Mat Sci & Engn, State Key Lab New Ceram & Fine Proc, Beijing 100084, Peoples R China Peking Univ, Minist Educ Beijing, Mol Oncol Lab, Key Lab Carcinogenesis & Translat Res,Can Hosp &, Beijing 100142, Peoples R China Peking Univ, Dept Orthoped, Hosp 3, Beijing 100191, Peoples R China |
| Keywords | ELECTROSPUN NANOFIBERS GUIDANCE CONDUITS BONE-FORMATION IN-VIVO REGENERATION SCAFFOLDS INJURY GAP DIFFERENTIATION ALIGNMENT |
| Issue Date | 2020 |
| Publisher | THERANOSTICS |
| Abstract | Autologous nerve transplantation, which is the gold standard for clinical treatment of peripheral nerve injury, still has many limitations. In this study, aligned chitosan fiber hydrogel (ACG) grafted with a bioactive peptide mixture consisting of RGI (Ac-RGIDKRHWNSQGG) and KLT (Ac-KLTWQELYQLKYKGIGG), designated as ACG-RGI/KLT, was used as nerve conduit filler to repair sciatic nerve defects in rats. Methods: Chitosan nanofiber hydrogel was prepared by a combination of electrospinning and mechanical stretching methods, and was then grafted with RGI and KLT, which are peptides mimicking brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), respectively. The physicochemical properties of ACG-RGI/KLT were fully characterized. In vitro, the distribution, proliferation, and secretory activity of Schwann cells were analyzed. Next, the in vivo repair potential for 15-mm rat sciatic nerve defects was examined. The recovery of regenerated nerve, muscle, and motor function was evaluated by neuromuscular histology, electrophysiology, and catwalk gait analysis. Results: We first constructed directionally aligned chitosan nanofiber hydrogel grafted with RGI/KLT peptide mixture (ACG-RGI/KLT). ACG-RGI/KLT oriented the Schwann cells, and promoted the proliferation and secretion of neurotrophic factors by Schwann cells. At an early injury stage, ACG-RGI/KLT not only enhanced nerve regeneration, but also promoted vascular penetration. At 12 weeks, ACG-RGI/KLT facilitated nerve regeneration and functional recovery in rats. Conclusions: Aligned chitosan nanofiber hydrogel grafted with RGI/KLT peptide provides an effective means of repairing sciatic nerve defects and shows great potential for clinical application. |
| URI | http://hdl.handle.net/20.500.11897/585032 |
| ISSN | 1838-7640 |
| DOI | 10.7150/thno.36272 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 第三医院 |
