Healing Mechanisms in Cutaneous Wounds: Tipping the Balance

Abstract

Acute and chronic cutaneous wounds pose a significant health and economic burden. Cutaneous wound healing is a complex process that occurs in four distinct, yet overlapping, highly coordinated stages: hemostasis, inflammation, proliferation, and remodeling. Postnatal wound healing is reparative, which can lead to the formation of scar tissue. Regenerative wound healing occurs during fetal development and in restricted postnatal tissues. This process can restore the wound to an uninjured state by producing new skin cells from stem cell reservoirs, resulting in healing with minimal or no scarring. Focusing on the pathophysiology of acute burn wounds, this review highlights reparative and regenerative healing mechanisms (including the role of cells, signaling molecules, and the extracellular matrix) and discusses how components of regenerative healing are being used to drive the development of novel approaches and therapeutics aimed at improving clinical outcomes. Important components of regenerative healing, such as stem cells, growth factors, and decellularized dermal matrices, are all being evaluated to recapitulate more closely the natural regenerative healing process. Impact Statement Acute wounds from thermal injury are common; they exert substantial physical and psychological effects on a patient and result in significant morbidity and mortality. This review provides a detailed overview of the mechanisms of reparative and regenerative wound healing; discusses the key cell types, signaling molecules, and molecular targets that influence these important biological pathways; and highlights current therapeutic approaches aimed at promoting regenerative wound healing. An increased understanding of the underlying mechanisms of reparative and regenerative healing will contribute to the development of innovative strategies for the clinical treatment of patients with severe burns.

Accelerated Angiogenesis of Human Umbilical Vein Endothelial Cells Under Negative Pressure Was Associated With the Regulation of Gene Expression Involved in the Proliferation and Migration

“…Previous studies have shown that negative pressure promotes the restoration of injured tissue by enhancing cell growth in vivo 8,9 . To elucidate the mechanism involved in the enhancement of cell growth by negative pressure, we first examined whether negative pressure influenced oxygen utilization by cells.…”

“…Previous studies have shown that negative pressure promotes the restoration of injured tissue by enhancing cell growth in vivo. 8,9 To elucidate the mechanism involved in the enhancement of cell growth by negative pressure, we first examined whether negative pressure influenced oxygen utilization by cells. The concentration of oxygen in the culture medium under negative pressure did not decrease compared with that under normal pressure (see Figure, Supplemental Digital Content 1A, http://links.lww.com/SAP/A782, which shows oxygen concentration).…”

“…The process of wound healing is characterized by 3 steps, namely, inflammation, new tissue formation, and remodeling. Platelets, macrophages, endothelial cells, keratinocytes, and fibroblasts are the main cell types involved in re-epithelialization and granulation tissue formation 1,8,9 . In the wound bed, platelets and macrophages continue to supply growth factors, thereby promoting angiogenesis by endothelial cells and stimulating fibroblasts.…”

Poloxamer 407 and Hyaluronic Acid Thermosensitive Hydrogel-Encapsulated Ginsenoside Rg3 to Promote Skin Wound Healing

“…Wound healing, a complex coordinated process subjected to many intrinsic and exogenous imbalances, is an evolved dynamic biological process essential for species’ survival. Wound healing involves tightly controlled biochemical and cellular events, such as inflammation, proliferation, and remodeling, which occur sequentially in a continuous and sometimes overlapping fashion ( Wang P.-H. et al, 2018 ; Oryan et al, 2019 ; Singer, 2022 ). The main goal of tissue regeneration in wound healing is the speed and quality of healing to effectively regenerate new healthy epidermis and lead to better cosmetic results.…”

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“…Wound healing, a complex coordinated process subjected to many intrinsic and exogenous imbalances, is an evolved dynamic biological process essential for species' survival. Wound healing involves tightly controlled biochemical and cellular events, such as inflammation, proliferation, and remodeling, which occur sequentially in a continuous and sometimes overlapping fashion (Wang P.-H. et al, 2018;Oryan et al, 2019;Singer, 2022). The main goal of tissue regeneration in wound healing is the speed and quality of healing to effectively regenerate new healthy epidermis and lead to better cosmetic results.…”