A multi-modal delivery strategy for spinal cord regeneration using a composite hydrogel presenting biophysical and biochemical cues synergistically
A multi-modal delivery strategy for spinal cord regeneration using a composite hydrogel presenting biophysical and biochemical cues synergistically
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使用复合水凝胶进行脊髓再生的多模式递送策略，协同呈现生物物理和生化线索
DOI：
10.1016/j.biomaterials.2021.120971
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发表时间：
2021
期刊：
影响因子：
14
通讯作者：
Wang Xiumei
中科院分区：
文献类型：
--
作者：
Man Weitao;Yang Shuhui;Cao Zheng;Lu Jiaju;Kong Xiangdong;Sun Xiaodan;Zhao Lingyun;Guo Yi;Yao Shenglian;Wang Guihuai;Wang Xiumei
大量的组织工程研究支持可植入的装载生物活性线索的支架增强脊髓再生。然而，单线索递送的支架效果不理想，很可能是由于病变区域敌对生态位的复杂性。在这方面，多模式递送多种异质细胞调控线索的策略是加强脊髓修复的未满足需求，这需要对与脊髓损伤相关的再生生态位有透彻的了解。本文将纤维蛋白水凝胶（AFG）与功能化自组装肽（fSAP）结合，设计了一种具有互穿网络特征的多功能纳米纤维复合水凝胶（AFG /fSAP）。作为生物物理和生化信号的来源，AFG/fSAP可以通过引导再生组织、加速轴突再生和髓鞘再生以及促进血管生成来促进脊髓再生。在多种线索的协同作用下，AFG/fSAP植入有助于脊髓半切大鼠的解剖、电生理和运动功能恢复。本研究为中枢神经系统再生提供了一种新的多模式方法，为脊髓损伤的临床应用提供了可能。
Extensive tissue engineering studies have supported the enhanced spinal cord regeneration by implantable scaffolds loaded with bioactive cues. However, scaffolds with single-cue delivery showed unsatisfactory effects, most likely due to the complex nature of hostile niches in the lesion area. In this regard, strategies of multi-modal delivery of multiple heterogeneous cell-regulatory cues are unmet needs for enhancing spinal cord repair, which requires a thorough understanding of the regenerative niche associated with spinal cord injury. Here, by combining hierarchically aligned fibrin hydrogel (AFG) and functionalized self-assembling peptides (fSAP), a novel multifunctional nanofiber composite hydrogel AFG/fSAP characterized with interpenetrating network is designed. Serving as a source of both biophysical and biochemical cues, AFG/fSAP can facilitate spinal cord regeneration via guiding regenerated tissues, accelerating axonal regrowth and remyelination, and promoting angiogenesis. Giving the synergistic effect of multiple cues, AFG/fSAP implantation contributes to anatomical, electrophysiological, and motor functional restorations in rats with spinal cord hemisection. This study provides a novel multi-modal approach for regeneration in central nervous system, which has potentials for clinical practice of spinal cord injury.