National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, Sichuan, China.
Department of Neurosurgery, West China Medical School, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
Carbohydr Polym. 2022 Feb 15;278:118961. doi: 10.1016/j.carbpol.2021.118961. Epub 2021 Dec 4.
Either oriented architecture or viscoelasticity is pivotal to neurogenesis, thus, native neural extracellular matrix derived-hyaluronan hydrogels with nano-orientation and viscoelasticity recapitulated might be instructive for neurogenesis, however it is still unexploited. Herein, based on aldehyde-methacrylate difunctionalized hyaluronan, by integrating imine kinetic modulation and microfluidic biofabrication, we construct a hydrogel system with orthogonal viscoelasticity and nano-topography. We then find the positive synergy effects of matrix nano-orientation and viscoelasticity not only on neurites outgrowth and elongation of neural cells, but also on neuronal differentiation of stem cells. Moreover, by implanting viscoelastic and nano-aligned hydrogels into lesion sites, we demonstrate the enhanced repair of spinal cord injury, including ameliorated pathological microenvironment, facilitated endogenous neurogenesis and functional axons regeneration as well as motor function restoration. This work supplies universal platform for preparing neuronal inducing hyaluronan-based hydrogels which might serve as promising therapeutic strategies for nerve injury.
无论是定向架构还是粘弹性对于神经发生都至关重要，因此，具有纳米取向和粘弹性的天然神经细胞外基质衍生透明质酸水凝胶的重现可能对神经发生具有指导意义，但目前尚未得到充分利用。在此，我们基于醛基-甲基丙烯酰胺双官能化透明质酸，通过整合亚胺动力学调节和微流控生物制造，构建了具有正交粘弹性和纳米形貌的水凝胶体系。然后，我们发现基质纳米取向和粘弹性的协同作用不仅对神经细胞的突起生长和伸长有积极影响，而且对干细胞的神经元分化也有积极影响。此外，通过将粘弹性和纳米排列水凝胶植入损伤部位，我们证明了对脊髓损伤的修复作用增强，包括改善病理性微环境、促进内源性神经发生和功能轴突再生以及运动功能恢复。这项工作为制备神经元诱导透明质酸水凝胶提供了通用平台，可能为神经损伤提供有前景的治疗策略。
