Regulation of Schwann Cell and DRG Neurite Behaviors within Decellularized Peripheral Nerve Matrix,ACS Applied Materials & Interfaces

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Regulation of Schwann Cell and DRG Neurite Behaviors within Decellularized Peripheral Nerve Matrix
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2022-02-11 , DOI: 10.1021/acsami.1c20320
Wen Xue _{1,

2} , Yunfan Kong _{1,

2} , Rafay Abu ₃ , Pooja Roy _{1,

4} , Sung-Ho Huh _{1,

4} , Mitchell Kuss _{1,

2} , Vikas Kumar _{3,

5} , Bin Duan _{1,

2,

6,

7}

Affiliation

Decellularized nerve hydrogels (dNHs) containing bioactive molecules are promising biomaterials for peripheral nerve injury (PNI) treatment and have been extensively applied in clinical and preclinical practice. However, most previous research projects studied their influences on nerve-related cellular behaviors in two dimensions (2D) without taking hydrogel biomechanics into consideration. The molecular mechanisms underlying the beneficial microenvironment provided by dNHs also remain unclear. In this study, dNHs from rat sciatic nerves were prepared, and their effects on Schwann cell (SC) and dorsal root ganglion (DRG) neurite behaviors were evaluated and compared to commercial rat tail type I collagen (Col) hydrogels in three-dimensional (3D) environments. We found that dNHs could promote SC proliferation and neurite outgrowth, and both the hydrogel mechanics and components contributed to the dNH functionalization. Through proteomics analysis, we found that laminin (LAM) and type V collagen (COLV) exclusively and abundantly existed in dNHs. By adding exogenous LAM and COLV into Col hydrogels, we demonstrated that they regulated SC gene expression and that LAM could promote SC spreading and neurite outgrowth, while COLV improved SC proliferation. Lastly, dNHs were fabricated into paper-like, aligned nerve scaffolds through unidirectional freezing to expand the dNH applications in PNI treatment.

中文翻译：

去细胞外周神经基质中雪旺细胞和 DRG 神经突行为的调节

含有生物活性分子的脱细胞神经水凝胶（dNHs）是治疗周围神经损伤（PNI）的有前途的生物材料，并已广泛应用于临床和临床前实践。然而，大多数先前的研究项目在没有考虑水凝胶生物力学的情况下，研究了它们对二维 (2D) 神经相关细胞行为的影响。dNH 提供的有益微环境的分子机制也仍不清楚。在这项研究中，制备了来自大鼠坐骨神经的 dNH，评估了它们对雪旺细胞 (SC) 和背根神经节 (DRG) 神经突行为的影响，并与商业大鼠尾 I 型胶原蛋白 (Col) 水凝胶进行了三维比较。 3D) 环境。我们发现 dNHs 可以促进 SC 增殖和神经突生长，水凝胶力学和组分都有助于 dNH 功能化。通过蛋白质组学分析，我们发现层粘连蛋白 (LAM) 和 V 型胶原蛋白 (COLV) 仅且大量存在于 dNHs 中。通过将外源性 LAM 和 COLV 添加到 Col 水凝胶中，我们证明它们可以调节 SC 基因表达，并且 LAM 可以促进 SC 扩散和神经突生长，而 COLV 可以改善 SC 增殖。最后，通过单向冷冻将 dNH 制成纸状排列的神经支架，以扩大 dNH 在 PNI 治疗中的应用。我们证明了它们调节 SC 基因表达，并且 LAM 可以促进 SC 扩散和神经突生长，而 COLV 可以改善 SC 增殖。最后，通过单向冷冻将 dNH 制成纸状排列的神经支架，以扩大 dNH 在 PNI 治疗中的应用。我们证明了它们调节 SC 基因表达，并且 LAM 可以促进 SC 扩散和神经突生长，而 COLV 可以改善 SC 增殖。最后，通过单向冷冻将 dNH 制成纸状排列的神经支架，以扩大 dNH 在 PNI 治疗中的应用。

更新日期：2022-02-11

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