A Thermosensitive Heparin-Poloxamer Hydrogel Bridges aFGF to Treat Spinal Cord Injury
A Thermosensitive Heparin-Poloxamer Hydrogel Bridges aFGF to Treat Spinal Cord Injury
复制标题
热敏肝素-泊洛沙姆水凝胶桥接 aFGF 治疗脊髓损伤。
DOI：
10.1021/acsami.6b13155
复制
发表时间：
2017-03-01
影响因子：
9.5
通讯作者：
Xiao, Jian
中科院分区：
文献类型：
--
作者：
Wang, Qingqing;He, Yan;Xiao, Jian
酸性成纤维细胞生长因子(AFGF)对脊髓损伤(SCI)有保护作用，但其理化稳定性差，不能通过血脊髓屏障(BSCB)。作为一种很有前途的生物材料，水凝胶含有大量的水和三维多孔结构，通常用于负载和输送生长因子。肝素不仅可以提高生长因子在水凝胶上的载量，而且可以稳定水凝胶的结构，控制其释放行为。为此，我们开发了一种新型的载人碱性成纤维细胞生长因子的温敏性肝素-泊洛沙姆水凝胶，并将其应用于脊髓损伤后的保护和再生。为了评价aFGF-HP水凝胶的效果，在体内和体外研究了bSCB修复、神经元和轴突修复、胶质瘢痕抑制、炎症反应抑制和运动恢复的效果。结果表明，该水凝胶具有较好的缓释作用，对体外培养的人成纤维细胞生长因子具有保护作用。无论在体内还是体外，与单纯静脉注射HP水凝胶组和单纯静注组相比，aFGF-HP水凝胶组BSCB的破坏程度显著减轻，神经细胞凋亡减少，反应性星形胶质细胞增生减少，神经元和轴突修复增加。本研究为促进脊髓损伤后的恢复提供了有效途径，为脊髓损伤的保护提供了成功的策略。
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.