A Thermosensitive Heparin-Poloxamer Hydrogel Bridges aFGF to Treat Spinal Cord Injury.
Acidic fibroblast growth factor (aFGF) exerts a protective effect on spinal cord injury (SCI) but is limited by the lack of physicochemical stability and the ability to cross the blood spinal cord barrier (BSCB). As promising biomaterials, hydrogels contain substantial amounts of water and a three-dimensional porous structure and are commonly used to load and deliver growth factors. Heparin can not only enhance growth factor loading onto hydrogels but also can stabilize the structure and control the release behavior. Herein, a novel aFGF-loaded thermosensitive heparin-poloxamer (aFGF-HP) hydrogel was developed and applied to provide protection and regeneration after SCI. To assess the effects of the aFGF-HP hydrogel, BSCB restoration, neuron and axonal rehabilitation, glial scar inhibition, inflammatory response suppression, and motor recovery were studied both in vivo and in vitro. The aFGF-HP hydrogels exhibited sustained release of aFGF and protected the bioactivity of aFGF in vitro. Compared to groups intravenously administered either drug-free HP hydrogel or aFGF alone, the aFGF-HP hydrogel group revealed prominent and attenuated disruption of the BSCB, reduced neuronal apoptosis, reactive astrogliosis, and increased neuron and axonal rehabilitation both in vivo and in vitro. This work provides an effective approach to enhance recovery after SCI and provide a successful strategy for SCI protection.
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.|WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Qingqing
Q
Wang
WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.|UQ-WMU Joint Research Group for Regenerative Medicine, Oral Health Centre, University of Queensland , Brisbane 4006, Australia.
Yan
Y
He
WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Yingzheng
Y
Zhao
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu 610041, China.
Huixu
http://orcid.org/0000-0003-1998-4727
H
Xie
WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Qian
Q
Lin
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.|WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Zili
Z
He
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.
Xiaoyan
X
Wang
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.|WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Jiawei
J
Li
WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Hongyu
H
Zhang
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.|WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Chenggui
C
Wang
WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Fanghua
F
Gong
WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Xiaokun
X
Li
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.|WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Huazi
H
Xu
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.|WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.|UQ-WMU Joint Research Group for Regenerative Medicine, Oral Health Centre, University of Queensland , Brisbane 4006, Australia.
Qingsong
Q
Ye
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University , Wenzhou, Zhejiang 325035, China.|WMU-JCU Joint Research Group for Stem Cell and Tissue Engineering, School of Pharmaceutical Sciences, Wenzhou Medical University , Wenzhou 325035, China.
Jian
http://orcid.org/0000-0001-7374-6506
J
Xiao
D000818:Animals; D016220:Fibroblast Growth Factor 1; D006493:Heparin; D020100:Hydrogels; D020442:Poloxamer; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries
D020100:Hydrogels; D016220:Fibroblast Growth Factor 1; D020442:Poloxamer; D006493:Heparin
acidic fibroblast growth factor; control release; neuroprotection; spinal cord injury; thermosensitive hydrogel