Mixed Composition Microribbon Hydrogels Induce Rapid and Synergistic Cartilage Regeneration by Mesenchymal Stem Cells in 3D via Paracrine Signaling Exchange,ACS Biomaterials Science & Engineering

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Mixed Composition Microribbon Hydrogels Induce Rapid and Synergistic Cartilage Regeneration by Mesenchymal Stem Cells in 3D via Paracrine Signaling Exchange
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-05-27 , DOI: 10.1021/acsbiomaterials.0c00131
Courtney Gegg ₁ , Xinming Tong ₂ , Fan Yang ₃

Affiliation

Hydrogels are widely used matrices for mesenchymal stem cell (MSC)-based cartilage regeneration but often result in slow cartilage deposition with inferior mechanical strength. We recently reported a gelatin-based microribbon (μRB) scaffold, which contains macroporosity and substantially enhances the speed of cartilage formation by MSCs in 3D. However, our previous method cannot be used to fabricate different polymers into μRBs, and the effects of varying μRB compositions on MSC cartilage regeneration in 3D remain unknown. Here, we report a method that allows fabricating different polymers [gelatin, chondroitin sulfate, hyaluronic acid, and polyethylene glycol (PEG)] into μRB structures, which can be mixed in any ratio and cross-linked into 3D scaffolds in a modular manner. Mixing glycosaminoglycan μRBs with gelatin or PEG μRBs induced great synergy, resulting in fast cartilage deposition. After only 3 weeks of culture, leading mixed μRB composition reached high compressive strength on par with native cartilage. Such synergy can be recapitulated via exchange of soluble factors secreted by MSCs seeded in different μRB compositions in a dose-dependent manner. Tuning the ratio of mixed μRB compositions allowed further optimization of the quantity and speed of cartilage regeneration by MSCs. Together, our results validate mixed μRB compositions as a novel biomaterial tool for inducing synergy and accelerating MSC-based cartilage regeneration with biomimetic mechanical properties through paracrine signal exchange.

中文翻译：

混合成分微带水凝胶通过旁分泌信号交换诱导间充质干细胞在 3D 中快速协同软骨再生

水凝胶是广泛用于基于间充质干细胞 (MSC) 的软骨再生的基质，但通常会导致软骨沉积缓慢且机械强度较差。我们最近报道了一种基于明胶的微带 (μRB) 支架，它含有大孔隙，可显着提高 MSC 在 3D 中形成软骨的速度。然而，我们以前的方法不能用于将不同的聚合物制成 μRB，并且不同 μRB 成分对 3D MSC 软骨再生的影响仍然未知。在这里，我们报告了一种允许将不同的聚合物 [明胶、硫酸软骨素、透明质酸和聚乙二醇 (PEG)] 制造成 μRB 结构的方法，这些结构可以任意比例混合并以模块化方式交联成 3D 支架。将糖胺聚糖 μRB 与明胶或 PEG μRB 混合会产生巨大的协同作用，从而导致软骨快速沉积。经过仅 3 周的培养，领先的混合 μRB 组合物达到了与天然软骨相当的高抗压强度。这种协同作用可以概括通过以剂量依赖的方式交换接种在不同 μRB 组合物中的 MSC 分泌的可溶性因子。调整混合 μRB 组合物的比例可以进一步优化 MSC 软骨再生的数量和速度。总之，我们的结果验证了混合 μRB 组合物作为一种新型生物材料工具，可通过旁分泌信号交换诱导协同作用并加速具有仿生机械特性的基于 MSC 的软骨再生。

更新日期：2020-07-13

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