Harvard-MIT Program in Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Tissue Eng Part A. 2021 Dec;27(23-24):1447-1457. doi: 10.1089/ten.tea.2020.0332. Epub 2021 May 12.
Gap closure is a dynamic process in wound healing, in which a wound contracts and a provisional matrix is laid down, to restore structural integrity to injured tissues. The efficiency of wound closure has been found to depend on the shape of a wound, and this shape dependence has been echoed in various studies. While wound shape itself appears to contribute to this effect, it remains unclear whether the alignment of the surrounding extracellular matrix (ECM) may also contribute. In this study, we investigate the role both wound curvature and ECM alignment have on gap closure in a 3D culture model of fibrous tissue. Using microfabricated flexible micropillars positioned in rectangular and octagonal arrangements, seeded 3T3 fibroblasts embedded in a collagen matrix formed microtissues with different ECM alignments. Wounding these microtissues with a microsurgical knife resulted in wounds with different shapes and curvatures that closed at different rates. Observing different regions around the wounds, we noted local wound curvature did not impact the rate of production of provisional fibronectin matrix assembled by the fibroblasts. Instead, the rate of provisional matrix assembly was lowest emerging from regions of high fibronectin alignment and highest in the areas of low matrix alignment. Our data suggest that the underlying ECM structure affects the shape of the wound as well as the ability of fibroblasts to build provisional matrix, an important step in the process of tissue closure and restoration of tissue architecture. The study highlights an important interplay between ECM alignment, wound shape, and tissue healing that has not been previously recognized and may inform approaches to engineer tissues. Impact statement Current models of tissue growth have identified a role for curvature in driving provisional matrix assembly. However, most tissue repair occurs in fibrous tissues with different levels of extracellular matrix (ECM) alignment. Here, we show how this underlying ECM alignment may affect the ability of fibroblasts to build new provisional matrix, with implications for wound healing and providing insight for engineering of new tissues.
伤口闭合是伤口愈合过程中的一个动态过程，在此过程中，伤口会收缩并形成一个临时基质，以恢复受伤组织的结构完整性。已经发现伤口闭合的效率取决于伤口的形状，并且这一形状依赖性在各种研究中都得到了呼应。虽然伤口的形状本身似乎对这种效果有贡献，但目前尚不清楚周围细胞外基质 (ECM) 的排列是否也有贡献。在这项研究中，我们研究了在纤维组织的 3D 培养模型中，伤口曲率和 ECM 排列对伤口闭合的作用。通过使用定位在矩形和八角形排列中的微制造柔性微柱，将嵌入胶原基质中的 3T3 成纤维细胞接种到具有不同 ECM 排列的微组织中。用微手术刀对这些微组织进行创伤处理，会导致形成不同形状和曲率的伤口，这些伤口的闭合速度也不同。观察伤口周围的不同区域，我们注意到局部伤口曲率不会影响成纤维细胞组装临时纤维连接蛋白基质的速度。相反，临时基质组装的速度在纤维连接蛋白排列较高的区域最低，在基质排列较低的区域最高。我们的数据表明，底层 ECM 结构不仅会影响伤口的形状，还会影响成纤维细胞构建临时基质的能力，这是组织闭合和恢复组织结构的重要步骤。该研究强调了 ECM 排列、伤口形状和组织愈合之间的重要相互作用，这一点以前尚未被认识到，可能为组织工程提供信息。影响陈述 当前的组织生长模型已经确定了曲率在驱动临时基质组装中的作用。然而，大多数组织修复发生在具有不同细胞外基质 (ECM) 排列水平的纤维组织中。在这里，我们展示了这种底层 ECM 排列如何影响成纤维细胞构建新的临时基质的能力，这对伤口愈合有影响，并为新组织的工程提供了深入的了解。
