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ROS-Scavenging Hydrogels Synergize with Neural Stem Cells to Enhance Spinal Cord Injury Repair via Regulating Microenvironment and Facilitating Nerve Regeneration
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2023-03-29 , DOI: 10.1002/adhm.202300123
Dun Liu 1 , Geng Lu 2 , Bo Shi 1 , Huanyu Ni 3 , Jun Wang 2 , Yong Qiu 1 , Lin Yang 4 , Zezhang Zhu 1 , Xuan Yi 5 , Xiao Du 3 , Benlong Shi 1
Affiliation  

Although stem cell-based therapy is recognized as a promising therapeutic strategy for spinal cord injury (SCI), its efficacy is greatly limited by local reactive oxygen species (ROS)-abundant and hyper-inflammatory microenvironments. It is still a challenge to develop bioactive scaffolds with outstanding antioxidant capacity for neural stem cells (NSCs) transplantation. In this study, albumin biomimetic cerium oxide nanoparticles (CeO2@BSA nanoparticles, CeNPs) are prepared in a simple and efficient manner and dispersed in gelatin methacryloyl to obtain the ROS-scavenging hydrogel (CeNP-Gel). CeNP-Gel synergistically promotes neurogenesis via alleviating oxidative stress microenvironments and improving the viability of encapsulated NSCs. More interestingly, in the presence of CeNP-Gel, microglial polarization to anti-inflammatory M2 subtype are obviously facilitated, which is further verified to be associated with phosphoinositide 3-kinase/protein kinase B pathway activation. Additionally, the injectable ROS-scavenging hydrogel is confirmed to induce the integration and neural differentiation of transplanted NSCs. Compared with the blank-gel group, the survival rate of NSCs in CeNP-Gel group is about 3.5 times higher, and the neural differentiation efficiency is about 2.1 times higher. Therefore, the NSCs-laden ROS-scavenging hydrogel represents a comprehensive strategy with great application prospect for the treatment of SCI through comprehensively modulating the adverse microenvironment.

中文翻译:

ROS清除水凝胶与神经干细胞协同作用,通过调节微环境和促进神经再生来增强脊髓损伤修复

尽管基于干细胞的疗法被认为是脊髓损伤(SCI)的一种有前途的治疗策略,但其疗效受到局部活性氧(ROS)丰富和高炎症微环境的极大限制。开发具有出色抗氧化能力的用于神经干细胞(NSC)移植的生物活性支架仍然是一个挑战。本研究以简单高效的方式制备了白蛋白仿生氧化铈纳米颗粒(CeO 2 @BSA纳米颗粒,CeNPs)并将其分散在甲基丙烯酰明胶中以获得ROS清除水凝胶(CeNP-Gel)。CeNP-Gel 通过减轻氧化应激微环境和提高封装 NSC 的活力来协同促进神经发生。更有趣的是,在CeNP-Gel存在下,明显促进了小胶质细胞向抗炎M2亚型的极化,这被进一步证实与磷酸肌醇3激酶/蛋白激酶B通路激活有关。此外,可注射的ROS清除水凝胶被证实可以诱导移植的NSCs的整合和神经分化。与空白凝胶组相比,CeNP-Gel组NSCs的存活率约高3.5倍,神经分化效率约高2.1倍。因此,负载NSCs的ROS清除水凝胶代表了一种通过综合调节不良微环境来治疗SCI的具有巨大应用前景的综合策略。
更新日期:2023-03-29
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