4.5 Article

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

Journal

JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 108, Issue 1, Pages 551-562

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.xphs.2018.10.008

Keywords

DOPA-IGF-1; neurotrophic factors; hUCMSCs; neural regeneration applications

Funding

  1. National Natural Science Foundation of China [51473164, 81672263, 51673186]
  2. Program of Scientific Development of Jilin Province [20170520121JH, 20170520141JH]
  3. Japan Society for the Promotion of Science [GJHZ1519]
  4. Jilin Province [2017SYHZ0021]
  5. Chinese Academy of Sciences [GJHZ1519, 2017SYHZ0021]

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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. (C) 2019 Published by Elsevier Inc. on behalf of the American Pharmacists Association.

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