Biomaterial scaffolds are increasingly being used to drive tissue regeneration. The limited success so far in human tissues rebuilding and therapy application may be due to inadequacy of the functionality biomaterial scaffold. We developed a new decellularized method to obtain complete anatomical skin biomatrix scaffold in situ with extracellular matrix (ECM) architecture preserved, in this study. We described a skin scaffold map by integrated proteomics and systematically analyzed the interaction between ECM proteins and epidermal cells in skin microenvironment on this basis. They were used to quantify structure and function of the skin’s Matrisome, comprised of core ECM components and ECM-associated soluble signals that are key regulators of epidermal development. We especially revealed that ECM played a role in determining the fate of epidermal stem cells through hemidesmosome components. These concepts not only bring us a new understanding of the role of the skin ECM niche, they also provide an attractive combinational strategy based on tissue engineering principles with skin biomatrix scaffold materials for the acceleration and enhancement of tissue regeneration.

生物材料支架越来越多地用于驱动组织再生。迄今为止，在人体组织重建和治疗应用中取得的有限成功可能是由于功能性生物材料支架的不足。在这项研究中，我们开发了一种新的脱细胞方法，以原位获得完整的解剖学皮肤生物基质支架，并保留了细胞外基质（ECM）结构。我们通过综合蛋白质组学描述了皮肤支架图，并在此基础上系统分析了ECM蛋白与皮肤微环境中的表皮细胞之间的相互作用。它们用于量化皮肤基质的结构和功能，该基质由核心ECM成分和ECM相关的可溶性信号组成，这些信号是表皮发育的关键调节剂。我们特别揭示了ECM在通过半桥粒成分决定表皮干细胞命运方面发挥了作用。这些概念不仅使我们对皮肤ECM生态位的作用有了新的认识，而且还提供了一种基于组织工程原理与皮肤生物基质支架材料的有吸引力的组合策略，以促进和增强组织再生。