Tissue Engineering Research Group (TERG), Royal College of Surgeons in Ireland (RCSI), Dublin 2, Ireland.
Trinity Centre for Biomedical Engineering, The University of Dublin Trinity College (TCD), Dublin 2, Ireland.
Methods Mol Biol. 2022;2454:273-283. doi: 10.1007/7651_2021_351.
Tissue engineering solutions have been widely explored for enhanced healing of skin wounds. Diabetic foot ulcers (DFU) are particularly challenging wounds to heal for a variety of reasons, including aberrant ECM, dysregulation of vascularization, and persistent inflammation. Tissue engineering approaches, such as porous collagen-based scaffolds, have shown promise in replacing the current treatments of surgical debridement and topical treatments. Collagen-glycosaminoglycan scaffolds, which are FDA approved for diabetic foot ulcers, can benefit from further functionalization by incorporation of additional signaling factors or extracellular matrix molecules. One option for this is to incorporate matrix from a rejuvenated cell source, as wounds in younger patients heal more quickly. Induced pluripotent stem cells (iPS) are generated from somatic cells and share many functional similarities with embryonic stem cells (ES), while avoiding the ethical concerns. Fibroblasts differentiated from iPS cells have been shown to enrich their ECM with glycosaminoglycan (GAGs), collagen Type III and fibronectin, to have an increased ECM production, and to be pro-angiogenic. Here we describe a technique to grow matrix from post-iPS fibroblasts, and to develop a scaffold from this matrix, in combination with collagen, with the goal of enhancing wound healing. By activating scaffolds with extracellular matrix (ECM) from fibroblasts derived from an iPS source (post-iPSF), the scaffolds are enriched with beneficial elements like GAGs, collagen type III, fibronectin, and VEGF. We believe these scaffolds can enhance skin regeneration and that the techniques can be modified for other tissue engineering applications.
组织工程解决方案已广泛探索用于增强皮肤伤口的愈合。糖尿病足溃疡（DFU）由于多种原因，包括异常细胞外基质、血管生成失调和持续炎症，是一种特别具有挑战性的伤口，难以愈合。组织工程方法，如多孔胶原基支架，已显示出在替代目前的手术清创和局部治疗方面的潜力。已获得 FDA 批准用于治疗糖尿病足溃疡的胶原-糖胺聚糖支架，可以通过掺入其他信号因子或细胞外基质分子来进一步功能化。一种选择是掺入来自年轻细胞来源的基质，因为年轻患者的伤口愈合更快。诱导多能干细胞（iPS）是从体细胞产生的，与胚胎干细胞（ES）具有许多功能相似性，同时避免了伦理问题。已证明 iPS 细胞分化的成纤维细胞可以增加糖胺聚糖（GAG）、III 型胶原和纤维连接蛋白的含量，从而增加细胞外基质的产生，并具有促血管生成作用。在这里，我们描述了一种从 iPS 后成纤维细胞中生长基质并结合胶原蛋白开发支架的技术，旨在增强伤口愈合。通过用源自 iPS 源的成纤维细胞衍生的细胞外基质（ECM）激活支架（post-iPSF），支架富含 GAG、III 型胶原、纤维连接蛋白和 VEGF 等有益成分。我们相信这些支架可以增强皮肤再生，并且可以修改这些技术以用于其他组织工程应用。
