A Novel Approach via Surface Modification of Degradable Polymers With Adhesive DOPA-IGF-1 for Neural Tissue Engineering

一种利用粘附性 DOPA-IGF-1 对可降解聚合物进行表面改性的神经组织工程新方法

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作者:Yi Zhang, Zongliang Wang, Yu Wang, Linlong Li, Zhenxu Wu, Yoshihiro Ito, Xiaoyu Yang, Peibiao Zhang

Abstract

The highly damaging state of spinal cord injuries has provided much inspiration for the design of surface modification of the implants that can promote nerve regeneration and functional reconstruction. DOPA-IGF-1, a new recombinant protein designed in our previous study, exhibited strong binding affinity to titanium and significantly enhanced the growth of NIH3T3 cells on the surface of titanium with the same biological activity as IGF-1. In this article, surface modification of poly(lactide-co-glycolide) (PLGA) films with recombinant DOPA-IGF-1 was performed to promote the paracrine activity of human umbilical cord mesenchymal stem cells (hUCMSCs) by secreting neurotrophic factors. DOPA-IGF-1 exhibited the strongest binding ability to PLGA films than commercial IGF-1 and nonhydroxylated YKYKY-IGF-1. In vitro cultures of hUCMSCs on the modified PLGA films showed that DOPA-IGF-1@PLGA substrates significantly improved the proliferation, adhesion, and neurotrophic factors secretion of hUCMSCs, especially for nerve growth factor, as confirmed by qRT-PCR and western blot analysis. Subsequently, the acquired neurotrophic factors secreted by the hUCMSCs cultured on the DOPA-IGF-1@PLGA films obviously enhanced neurite outgrowth of PC12 cells. Taken together, PLGA substrates with DOPA-IGF-1 immobilization is a promising platform for neural tissue engineering via neurotrophic factors secretion from MSCs and should be further tested in vivo.

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