PMID- 28990762 OWN - NLM STAT- MEDLINE DCOM- 20190110 LR - 20190110 IS - 1944-8252 (Electronic) IS - 1944-8244 (Linking) VI - 9 IP - 43 DP - 2017 Nov 1 TI - Multichanneled Nerve Guidance Conduit with Spatial Gradients of Neurotrophic Factors and Oriented Nanotopography for Repairing the Peripheral Nervous System. PG - 37623-37636 LID - 10.1021/acsami.7b12567 [doi] AB - Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth. The gelatin-based conduits mimicked the fascicular architecture of natural nerve ECM. The multichanneled (MC) scaffolds, cross-linked with microbial transglutaminase, possessed sustainable mechanical stability. Meanwhile, the release profile of dual neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), exhibited a temporal-controlled manner. In vitro, the differentiated neural stem cells effectively extended their neurites along the aligned nanofibers. Besides, in the treated group, the cell density increased in high NGF concentration regions of the gradient membrane, and the BDNF significantly promoted myelination. In a rabbit sciatic nerve transection in vivo model, the MC/AN/NG scaffold showed superior nerve recovery and less muscle atrophy comparable to autograft. By integrating multiple strategies to promote peripheral nerve regeneration, the MC/AN/NG scaffolds as nerve guidance conduits showed promising results and efficacious treatment alternatives for autologous nerve grafts. FAU - Chang, Yo-Cheng AU - Chang YC FAU - Chen, Ming-Hong AU - Chen MH AD - Department of Neurosurgery, Cathay General Hospital , Taipei 106, Taiwan. FAU - Liao, Shih-Yung AU - Liao SY FAU - Wu, Hsi-Chin AU - Wu HC AD - Department of Materials Engineering, Tatung University , Taipei 10491, Taiwan. FAU - Kuan, Chen-Hsiang AU - Kuan CH FAU - Sun, Jui-Sheng AU - Sun JS FAU - Wang, Tzu-Wei AU - Wang TW AUID- ORCID: 0000-0003-0669-6240 LA - eng PT - Journal Article DEP - 20171017 PL - United States TA - ACS Appl Mater Interfaces JT - ACS applied materials & interfaces JID - 101504991 SB - IM MH - Animals MH - Nanofibers MH - Nanostructures MH - Nerve Regeneration MH - *Peripheral Nerves MH - Rabbits MH - Sciatic Nerve MH - Tissue Scaffolds OTO - NOTNLM OT - multichanneled biomimetic structure OT - nanotopography OT - neurotrophic concentration gradient OT - sequential controlled release OT - tissue engineering EDAT- 2017/10/11 06:00 MHDA- 2019/01/11 06:00 CRDT- 2017/10/10 06:00 PHST- 2017/10/11 06:00 [pubmed] PHST- 2019/01/11 06:00 [medline] PHST- 2017/10/10 06:00 [entrez] AID - 10.1021/acsami.7b12567 [doi] PST - ppublish SO - ACS Appl Mater Interfaces. 2017 Nov 1;9(43):37623-37636. doi: 10.1021/acsami.7b12567. Epub 2017 Oct 17.