Heparin-based coacervate of bFGF facilitates peripheral nerve regeneration by inhibiting endoplasmic reticulum stress following sciatic nerve injury
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Rui Li1,*, Shuang Zou1,*, Yanqing Wu2, Yiyang Li1, Sinan Khor5, Yuqin Mao1, Huacheng He2, Ke Xu2, Hongyu Zhang1, Xiaokun Li2, Jian Wang3, Huai Jiang4, Qike Jin4, Qingsong Ye1, Zhouguang Wang1 and Jian Xiao1
1Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
2The Institute of Life Sciences, Wenzhou University, Wenzhou, Zhejiang 325035, China
3Department of Peripheral Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
4Department of Neonatology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
5Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
*These authors have contributed equally to this work
Zhouguang Wang, email: email@example.com
Jian Xiao, email: firstname.lastname@example.org
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
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.
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