The interplay between extracellular matrix and progenitor/stem cells during wound healing: Opportunities and future directions

Skin wound healing, a dynamic physiological process, progresses through coordinated overlapping phases to restore skin integrity. In some pathological conditions such as diabetes, wounds become chronic and hard-to-heal resulting in substantial morbidity and healthcare costs. Despite much advancement in understanding mechanisms of wound healing, chronic and intractable wounds are still a considerable challenge to nations' health care systems. Extracellular matrix (ECM) components play pivotal roles in all phases of wound healing. Therefore, a better understanding of their roles during wound healing can help improve wound care approaches. The ECM provides a 3D structure and forms the stem cell niche to support stem cell adhesion and survival and to regulate stem cell behavior and fate. Also, this dynamic structure reserves growth factors, regulates their bioavailability and provides biological signals. In various diseases, the composition and stiffness of the ECM is altered, which as a result, disrupts bidirectional cell-ECM interactions and tissue regeneration. Hence, due to the impact of ECM changes on stem cell fate during wound healing and the possibility of exploring new strategies to treat chronic wounds through manipulation of these interactions, in this review, we will discuss the importance/impact of ECM in the regulation of stem cell function and behavior to find ideal wound repair and regeneration strategies. We will also shed light on the necessity of using ECM in future wound therapy and highlight the potential roles of various biomimetic and ECM-based scaffolds as functional ECM preparations to mimic the native stem cell niche.