Double crosslinked biomimetic composite hydrogels containing topographical cues and WAY-316606 induce neural tissue regeneration and functional recovery after spinal cord injury.
Double crosslinked biomimetic composite hydrogels containing topographical cues and WAY-316606 induce neural tissue regeneration and functional recovery after spinal cord injury.
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含有地形线索和 WAY-316606 的双交联仿生复合水凝胶诱导脊髓损伤后神经组织再生和功能恢复
DOI：
10.1016/j.bioactmat.2022.12.024
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发表时间：
2023-06
影响因子：
18.9
通讯作者：
Liu, Jia
中科院分区：
文献类型：
--
作者：
Zhao, Xingchang;Lu, Xianzhe;Li, Kai;Song, Shiqiang;Luo, Zhaohui;Zheng, Chuanchuan;Yang, Chengliang;Wang, Xiumei;Wang, Liqiang;Tang, Yujin;Wang, Chong;Liu, Jia
脊髓损伤（SCI）是一种势不可挡且无法治愈的致残疾病，越来越多的多功能生物材料正在进行测试，但进展有限。有希望的材料应该是能够填充sci诱导的空腔并指导新神经元的生长，有效的药物负载可以改善局部微生物环境，促进神经组织再生。在这项研究中，构建了一种双交联仿生复合水凝胶，由脱细胞脊髓基质（ASCM）和明胶-丙烯酸化-β-环糊精-聚乙二醇二丙烯酸酯（G-CD-PEGDA）水凝胶组成，负载WAY-316606以激活典型的Wnt/β-catenin信号，并由一束三维打印排列的聚己内酯（PCL）微纤维增强。G-CD-PEGDA组分使复合水凝胶具有动态结构，具有自愈能力，有利于细胞迁移，ASCM组分促进神经细胞的亲和性和增殖。WAY-316606的扩散能够募集内源性神经干细胞，促进神经元分化。排列的PCL微纤维引导神经突纵向伸长。动物行为学研究进一步表明，复合水凝胶能显著恢复脊髓损伤后大鼠的运动功能。本研究提供了一种熟练的方法，以产生具有理想生理、化学和地形线索的多功能系统，用于治疗脊髓损伤患者。排列的微纤维模式为NSCs的迁移提供了定向的地形引导。复合水凝胶支架可促进NSCs向神经元的分化。负载way -316606的复合水凝胶支架激活Wnt/β-catenin信号通路，促进NSC分化。
Spinal cord injury (SCI) is an overwhelming and incurable disabling condition, for which increasing forms of multifunctional biomaterials are being tested, but with limited progression. The promising material should be able to fill SCI-induced cavities and direct the growth of new neurons, with effective drug loading to improve the local micro-organism environment and promote neural tissue regeneration. In this study, a double crosslinked biomimetic composite hydrogel comprised of acellularized spinal cord matrix (ASCM) and gelatin-acrylated-β-cyclodextrin-polyethene glycol diacrylate (designated G-CD-PEGDA) hydrogel, loaded with WAY-316606 to activate canonical Wnt/β-catenin signaling, and reinforced by a bundle of three-dimensionally printed aligned polycaprolactone (PCL) microfibers, was constructed. The G-CD-PEGDA component endowed the composite hydrogel with a dynamic structure with a self-healing capability which enabled cell migration, while the ASCM component promoted neural cell affinity and proliferation. The diffusion of WAY-316606 could recruit endogenous neural stem cells and improve neuronal differentiation. The aligned PCL microfibers guided neurite elongation in the longitudinal direction. Animal behavior studies further showed that the composite hydrogel could significantly recover the motor function of rats after SCI. This study provides a proficient approach to produce a multifunctional system with desirable physiological, chemical, and topographical cues for treating patients with SCI. The aligned microfiber pattern provided directional topographical guidance for NSCs to migrate. The composite hydrogel scaffold can promote the differentiation of NSCs into neurons. The WAY-316606-loaded composite hydrogel scaffolds activated Wnt/β-catenin signaling to promote NSC differentiation.
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