Interactions between extracellular matrix and growth factors in wound healing

Abstract

Dynamic interactions between growth factors and extracellular matrix (ECM) are integral to wound healing. These interactions take several forms that may be categorized as direct or indirect. The ECM can directly bind to and release certain growth factors (e.g., heparan sulfate binding to fibroblast growth factor-2), which may serve to sequester and protect growth factors from degradation, and/or enhance their activity. Indirect interactions include binding of cells to ECM via integrins, which enables cells to respond to growth factors (e.g., integrin binding is necessary for vascular endothelial growth factor-induced angiogenesis) and can induce growth factor expression (adherence of monocytes to ECM stimulates synthesis of platelet-derived growth factor). Additionally, matrikines, or subcomponents of ECM molecules, can bind to cell surface receptors in the cytokine, chemokine, or growth factor families and stimulate cellular activities (e.g., tenascin-C and laminin bind to epidermal growth factor receptors, which enhances fibroblast migration). Growth factors such as transforming growth factor-b also regulate the ECM by increasing the production of ECM components or enhancing synthesis of matrix degrading enzymes. Thus, the interactions between growth factors and ECM are bidirectional. This review explores these interactions, discusses how they are altered in difficult to heal or chronic wounds, and briefly considers treatment implications.

Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix

“…Interactions of GFs and the ECM modulate the partitioning of GFs from the ECM to the soluble phase and thus control their local concentration, diffusion, and signaling (1,2). For example, many GFs are able to bind the proteoglycan components of the ECM (2).…”

Expression of cytokines, growth factors and apoptosis-related signal molecules in chronic pressure ulcer wounds healing

“…Further, the wound microenvironment sequesters various growth factors and cytokines, inhibiting their functions resulting in delaying wound healing. 3 Cytokines and growth factors play major roles in wound healing by regulating cell proliferation, differentiation, migration and metabolism. In the process of wound healing, activated macrophages, fibroblasts, endothelial cells and other components release cytokines and growth factors, such as interleukin-1 (IL-1) and tumor necrosis factor-a (TNF-a), vascular endothelial growth factor (VEGF), fibroblast growth factors 2 (bFGF) and so on.…”

Aging Skin: Nourishing from Out-In. Lessons from Wound Healing

“…The rate of wound healing is dependent on effective synchronization of these phases [32]. The biological and/or chemical agent with the ability to influence the repair process could improve their synchronization, thus lowering healing time.…”