Multifunctional Biodegradable Conductive Hydrogel Regulating Microenvironment for Stem Cell Therapy Enhances the Nerve Tissue Repair

作者：Chao Xu, Ping Wu, Kun Yang, Congpu Mu, Binbin Li, Xiaokun Li, Zhouguang Wang, Zhongyuan Liu, Xinyu Wang, Zhiqiang Luo · 发表于：Small · 年份：2023 · DOI：10.1002/smll.202309793 · 被引用次数：70 · 研究领域：Nerve injury and regeneration、Graphene and Nanomaterials Applications、Neurogenesis and neuroplasticity mechanisms

The nerve guidance conduits incorporated with stem cells, which can differentiate into the Schwann cells (SCs) to facilitate myelination, shows great promise for repairing the severe peripheral nerve injury. The innovation of advanced hydrogel materials encapsulating stem cells, is highly demanded for generating supportive scaffolds and adaptive microenvironment for nerve regeneration. Herein, this work demonstrates a novel strategy in regulating regenerative microenvironment for peripheral nerve repair with a biodegradable conductive hydrogel scaffold, which can offer multifunctional capabilities in immune regulation, enhancing angiogenesis, driving SCs differentiation, and promoting axon regrowth. The biodegradable conductive hydrogel is constructed by incorporation of polydopamine-modified silicon phosphorus (SiP@PDA) nanosheets into a mixture of methacryloyl gelatin and decellularized extracellular matrix (GelMA/ECM). The biomimetic electrical microenvironment performs an efficacious strategy to facilitate macrophage polarization toward a pro-healing phenotype (M2), meanwhile the conductive hydrogel supports vascularization in regenerated tissue through sustained Si element release. Furthermore, the MSCs 3D-cultured in GelMA/ECM-SiP@PDA conductive hydrogel exhibits significantly increased expression of genes associated with SC-like cell differentiation, thus facilitating the myelination and axonal regeneration. Collectively, both the in vitro and in vivo studies demonstra...