Conventional nanoporous hydrogels often lead to slow cartilage deposition by MSCs in 3D due to physical constraints and requirement for degradation. Our group has recently reported macroporous gelatin microribbon (μRB) hydrogels, which substantially accelerate MSC-based cartilage formation in vitro compared to conventional gelatin hydrogels. To facilitate translating the use of μRB-based scaffolds for supporting stem cell-based cartilage regeneration in vivo, there remains a need to develop a customize-designed drug delivery system that can be incorporated into μRB-based scaffolds. Towards this goal, here we report polydopamine-coated mesoporous silica nanoparticles (MSNs) that can be stably incorporated within the macroporous μRB scaffolds, and allow tunable release of transforming growth factor (TGF)-β3. We hypothesize that increasing concentration of polydopamine coating on MSNs will slow down TGF- β3 release, and TGF-β3 release from polydopamine-coated MSNs can enhance MSC-based cartilage formation in vitro and in vivo. We demonstrate that TGF-β3 released from MSNs enhance MSC-based cartilage regeneration in vitro to levels comparable to freshly added TGF-β3 in the medium, as shown by biochemical assays, mechanical testing, and histology. Furthermore, when implanted in vivo in a mouse subcutaneous model, only the group containing MSN-mediated TGF-β3 release supported continuous cartilage formation, whereas control group without MSN showed loss of cartilage matrix and undesirable endochondral ossification. The modular design of MSN-mediated drug delivery can be customized for delivering multiple drugs with individually optimized release kinetics, and may be applicable to enhance regeneration of other tissue types.

中文翻译：

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基于微带的水凝胶纳米颗粒介导的 TGF-β 释放加速体内基于干细胞的软骨形成。

由于物理限制和降解要求，传统的纳米多孔水凝胶通常会导致 MSC 在 3D 中缓慢沉积软骨。我们小组最近报道了大孔明胶微带 (μRB) 水凝胶，与传统的明胶水凝胶相比，它在体外显着加速了基于 MSC 的软骨形成。为了促进基于 μRB 的支架在体内支持基于干细胞的软骨再生的使用，仍然需要开发一种定制设计的药物输送系统，该系统可以整合到基于 μRB 的支架中。为实现这一目标，我们在这里报道了聚多巴胺包被的介孔二氧化硅纳米粒子 (MSN)，它可以稳定地结合到大孔 μRB 支架中，并允许转化生长因子 (TGF)-β3 的可调释放。我们假设增加 MSN 上聚多巴胺涂层的浓度会减慢 TGF-β3 的释放，并且聚多巴胺涂层 MSN 释放的 TGF-β3 可以在体外和体内增强基于 MSC 的软骨形成。我们证明，从 MSNs 释放的 TGF-β3 在体外增强了基于 MSC 的软骨再生，其水平与培养基中新添加的 TGF-β3 相当，如生化测定、机械测试和组织学所示。此外，当体内植入小鼠皮下模型时，只有含有 MSN 介导的 TGF-β3 释放的组支持连续的软骨形成，而没有 MSN 的对照组显示出软骨基质的损失和不良的软骨内骨化。MSN 介导的药物递送的模块化设计可以定制，以递送具有单独优化的释放动力学的多种药物，