Multichanneled Nerve Guidance Conduit with Spatial Gradients of Neurotrophic Factors and Oriented Nanotopography for Repairing the Peripheral Nervous System

Yo Cheng Chang, Ming Hong Chen, Shih Yung Liao, Hsi Chin Wu, Chen Hsiang Kuan, Jui Sheng Sun, Tzu Wei Wang

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)37623-37636
Number of pages14
JournalACS Applied Materials and Interfaces
Volume9
Issue number43
DOIs
Publication statusPublished - Nov 1 2017
Externally publishedYes

Keywords

  • multichanneled biomimetic structure
  • nanotopography
  • neurotrophic concentration gradient
  • sequential controlled release
  • tissue engineering

ASJC Scopus subject areas

  • Materials Science(all)

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