Wound healing: a new management strategy

Abstract

Wound healing is a complex process whose understanding is constantly evolving. Until recently, the wound healing mechanism was imagined as a fibroproliferative response for producing a scaring, such as a repairing process. Recently, great attention has been addressed to biomaterials, stem cells, and bioengineered tissues. In this context, a new healthcare branch has developed: Regenerative Medicine. The healing process consists of three phases: the inflammatory reaction, cell proliferation (excessive or impaired), and extracellular matrix (ECM) remodelling. However, wound repair is usually characterised by the incomplete regeneration of the original tissue with hyperproduction of organised collagen, which can lead to new tissue production, with an 80% similarity to the original tissue. Also, impaired reparation leads to an abnormal fibroproliferative response, causing hypertrophic or keloid scars. Regenerative Medicine has promoted the study of tissue regeneration, mainly concerning the use of stem cells and electromagnetic applications. Consequently, the research developed in vitro and in vivo cellular models to investigate the tissue repair and regeneration process. Particular interest has been pointed to the role of humoral factors (cytokines and growth factors), genetic factors (genes expressed in the various phases of the process), and cellular factors. In addition,attention has been paid to fibroblasts, collagen, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs), agents fundamental for the extracellular matrix (ECM) remodelling. Thus, the new perspective shifted from inflammation to regeneration. This idea concerns treating the patient with skin and mucosal wounds, using local anti-inflammatory compounds targeting endothelial cells, ECM, anti-inflammatory cytokines, and MMPs. The regeneration pathway starts from the platelet activation leading to the recruitment of neutrophils (natural “debrider”), the release of TGF-b1, PDGF, TNF-a, and IL-1, and regulation of adhesion molecules expression. Macrophages are further recruited to ensure sustained debridement, release proinflammatory cytokines, and amplify the fibroproliferative response in the context of chronic inflammation. Macrophages include the M1 subpopulation, which is devoted to eliminating invading microorganisms and promoting the early inflammatory response. The M2 subpopulation aims to eliminate damaged cells and tissues and promote neoangiogenesis and tissue remodelling. In addition, ECM may amplify some mechanisms of the healing process. In conclusion, Regeneration Medicine represents the keystone for a new holistic approach to wound management.