Dermal Regeneration and Induction of Wound Closure in Diabetic Wounds

Abstract

This chapter reviews the biological and mechanical role of the extracellular matrix (ECM) in cutaneous wound healing. The multiplicity of viewpoints expressed in the literature, the lack of standards in evaluating research and surgical outcomes, and poor data quality have made our analysis challenging. We attempt to deliver a clear, objective analysis given these constraints. We highlight how chronic wounds impair the architecture of the ECM leading to a loss of structural and biochemical cues and halt healing. We also discuss how ECM scaffolds can be used therapeutically to repair or temporarily replace lost ECM, triggering healing, tissue regeneration, and ultimately effective wound closure. We further analyze biological characteristics, design principles, scientific evidence, and future challenges in the use of ECM scaffolds to treat chronic (diabetic) wounds. In particular, we debate the difference between bioactive ECM scaffolds that possess a regenerative capacity as stand-alone product and do not require pre-application (or simultaneous applications) of cells, and biological matrices designed as delivery methods of cells and growth factors. We discuss the elements of an “induced regeneration” theory that is organ nonspecific. Finally, we review the process behind the conception and development of a specific example of successful ECM scaffolds currently used for the treatment of diabetic chronic wounds.