Measuring human mesenchymal stem cell remodeling in hydrogels with a step-change in elastic modulus
Measuring human mesenchymal stem cell remodeling in hydrogels with a step-change in elastic modulus
复制标题
通过弹性模量的阶跃变化测量水凝胶中人间充质干细胞的重塑
DOI：
10.1039/d2sm00717g
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发表时间：
2022
期刊：
影响因子：
3.4
通讯作者：
Schultz, Kelly M.
中科院分区：
文献类型：
--
作者：
McGlynn, John A.;Schultz, Kelly M.
人类间充质干细胞（hMSC）在伤口愈合过程中发挥着重要作用。它们会响应愈合炎症阶段释放的化学信号，从原生生态位迁移到伤口。在伤口处，hMSCs下调炎症并调节组织再生。使用载有细胞的可植入水凝胶将额外的hMSCs递送到伤口具有改善愈合结果并重新启动慢性伤口愈合的潜力。为了使这些材料有效，细胞必须从支架迁移到天然组织中。这需要细胞在植入物-组织界面处穿越材料性质的阶跃变化。细胞在具有高度变化的性质的材料中的迁移没有得到很好的表征。我们测量3D封装的hMSC迁移和重塑在一个良好表征的水凝胶与刚度的阶跃变化。这种细胞可降解的水凝胶由与酶可降解肽交联的4臂聚（乙二醇）-己烯组成。支架由两个不同刚度的半部制成，这两个半部由刚度快速变化的界面分开。我们使用多粒子跟踪微流变学（MPT）表征细胞周围区域的结构和流变学变化。MPT测量嵌入颗粒的布朗运动，并将其与材料流变学联系起来。我们在包封后第1天测量到水凝胶的软区域中的重构多于硬区域，并且在第6天各处测量到类似的重构。在界面区域，我们测量了hMSC介导的沿着界面的重塑和向支架硬侧的迁移。这些结果可以改进设计用于从植入物到伤口的细胞递送的材料，以增强愈合。
Human mesenchymal stem cells (hMSCs) are instrumental in the wound healing process. They migrate to wounds from their native niche in response to chemical signals released during the inflammatory phase of healing. At the wound, hMSCs downregulate inflammation and regulate tissue regeneration. Delivering additional hMSCs to wounds using cell-laden implantable hydrogels has the potential to improve healing outcomes and restart healing in chronic wounds. For these materials to be effective, cells must migrate from the scaffold into the native tissue. This requires cells to traverse a step-change in material properties at the implant-tissue interface. Migration of cells in material with highly varying properties is not well characterized. We measure 3D encapsulated hMSC migration and remodeling in a well-characterized hydrogel with a step-change in stiffness. This cell-degradable hydrogel is composed of 4-arm poly(ethylene glycol)-norbornene cross-linked with an enzymatically-degradable peptide. The scaffold is made with two halves of different stiffnesses separated by an interface where stiffness changes rapidly. We characterize changes in structure and rheology of the pericellular region using multiple particle tracking microrheology (MPT). MPT measures Brownian motion of embedded particles and relates it to material rheology. We measure more remodeling in the soft region of the hydrogel than the stiff region on day 1 post-encapsulation and similar remodeling everywhere on day 6. In the interface region, we measure hMSC-mediated remodeling along the interface and migration towards the stiff side of the scaffold. These results can improve materials designed for cell delivery from implants to a wound to enhance healing.