Heparin-based coacervate of bFGF facilitates peripheral nerve regeneration by inhibiting endoplasmic reticulum stress following sciatic nerve injury

Abstract

// Rui Li 1, * , Shuang Zou 1, * , Yanqing Wu 2 , Yiyang Li 1 , Sinan Khor 5 , Yuqin Mao 1 , Huacheng He 2 , Ke Xu 2 , Hongyu Zhang 1 , Xiaokun Li 2 , Jian Wang 3 , Huai Jiang 4 , Qike Jin 4 , Qingsong Ye 1 , Zhouguang Wang 1 and Jian Xiao 1 1 Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China 2 The Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, China 3 Department of Peripheral Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China 4 Department of Neonatology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China 5 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA * These authors have contributed equally to this work Correspondence to: Zhouguang Wang, email: huaikongwang@126.com Jian Xiao, email: xfxj2000@126.com Keywords: peripheral nerve injury, controlled release, basic fibroblast growth factor, endoplasmic reticulum stress, coacervate Received: March 07, 2017      Accepted: April 29, 2017      Published: May 29, 2017 ABSTRACT Creating a microenvironment at the injury site that favors axonal regrowth and remyelinationis pivotal to the success of therapeutic reinnervation. The mature myelin sheath of the peripheral nervous system depends on active participation of Schwann cells to form new cytoskeletal components and tremendous amounts of relevant neurotrophic factors. In this study, we utilized a new biomaterial for growth factor delivery consisting of a biocompatible polycation, poly(ethylene argininylaspartatediglyceride) and heparin. It is capable of binding a variety of growth factors to deliver basic fibroblast growth factor (bFGF) through polyvalent ionic interactions for nerve repair. In vitro assays demonstrated that the bFGF loading efficiency reached 10 μg and this delivery vehicle could control the release of bFGF. In vivo , the coacervate enhanced bFGF bioavailability, which improved both motor and sensory function. It could also acceleratemyelinated fiber regeneration and remyelination and promote Schwann cells proliferation. Furthermore, the neuroprotective effect of bFGF-coacervate in sciatic nerve injury was associated with the alleviation of endoplasmic reticulum stress signal. This heparin-based delivery platform leads to increased bFGF loading efficiency and better controls its release, which will provide an effective strategy for peripheral nerve injury regeneration therapy.