The healing of an adult skin wound is a complex process requiring the collaborative efforts of many different tissues and cell lineages. The behavior of each of the contributing cell types during the phases of proliferation, migration, matrix synthesis, and contraction, as well as the growth factor and matrix signals present at a wound site, are now roughly understood. Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.

https://science.sciencemag.org/content/sci/276/5309/75.full.pdf

Wound Healing--Aiming for Perfect Skin Regeneration

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The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, and provides not only essential physical scaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue

/pdf/the-extracellular-matrix-at-a-glance-3w9rr8bw3e.pdf

The extracellular matrix at a glance

National Science Education Standards

The skin is the human body's largest organ, colonized by a diverse milieu of microorganisms, most of which are harmless or even beneficial to their host. Colonization is driven by the ecology of the skin surface, which is highly variable depending on topographical location, endogenous host factors and exogenous environmental factors. The cutaneous innate and adaptive immune responses can modulate the skin microbiota, but the microbiota also functions in educating the immune system. The development of molecular methods to identify microorganisms has led to an emerging view of the resident skin bacteria as highly diverse and variable. An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment.

The skin microbiome

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies.

/pdf/wound-repair-and-regeneration-mechanisms-signaling-and-3pcqcb79a0.pdf

Wound repair and regeneration: Mechanisms, signaling, and translation

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-β 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.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1524-475X.2009.00466.x

Interactions between extracellular matrix and growth factors in wound healing.

Wound Fluid from Chronic Leg Ulcers Contains Elevated Levels of Metalloproteinases MMP-2 and MMP-9

Degradation of fibronectin and vitronectin in chronic wound fluid: analysis by cell blotting, immunoblotting, and cell adhesion assays.

Open skin wounds are colonized with bacteria, and optimal wound care is required to prevent progression to infection. Intact skin normally provides protection from external environmental assaults. Disruption of the skin or tissue creating an open skin wound can result in infection, dehydration, hypothermia, scarring, compromised immunity, and changes in body image. Biofilms and bacterial genomics are areas of intense scientific investigation in the face of the emerging threat of bacterial resistance. Optimal wound care to prevent progression from colonization to infection remains the foundation of good clinical practice. On the basis of wound conditions, cleansing, debridement, measures to increase oxygenation and perfusion, adequate nutrition, and appropriate use of topical agents and antibiotics, when indicated, are the keys to managing open skin wounds. This article provides a targeted review of normal skin flora, wound healing, prevention of skin infection, colonization versus infection, biofilms, genomics and infectious disease, and management of open skin wounds.

Annette B. Wysocki

Papers

Interactions between extracellular matrix and growth factors in wound healing.

Wound Fluid from Chronic Leg Ulcers Contains Elevated Levels of Metalloproteinases MMP-2 and MMP-9

Degradation of fibronectin and vitronectin in chronic wound fluid: analysis by cell blotting, immunoblotting, and cell adhesion assays.

Evaluating and managing open skin wounds: colonization versus infection.

Fibronectin profiles in normal and chronic wound fluid.