Scarless wound healing: finding the right cells and signals

Abstract

From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. Yet effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and oral mucosa. However, many new advances have occurred over recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have already demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches to diminishing scar formation (Fig. 1). Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be redirected to a more fetal, scarless phenotype.

Hypertrophic scarring: the greatest unmet challenge after burn injury

“…These models can be used to study how to modulate the healing process to mimic that seen in tissues which do not scar. 81,82 …”

Learning from regeneration research organisms: The circuitous road to scar free wound healing

“…Granulation tissue is made up of new blood vessels, macrophages, fibroblasts and loose connective tissue and forms approximately 4 days after injury (Dreymueller et al, 2013; Jetten et al, 2014; MacLeod and Mansbridge, 2016; Sindrilaru and Scharffetter-Kochanek, 2013; Willenborg and Eming, 2014). Within hours of the injury, keratinocytes at the leading edge of the wound start to lose their apical-basal polarity and begin migrating into the wound (Balaji et al, 2015; Kawasumi et al, 2013; Leavitt et al, 2016; Penn et al, 2012; Romano and Sinha, 2011; Takeo et al, 2015; Walmsley et al, 2015). …”

“…In embryos the immune response consists of fewer numbers of less mature immune cells that stay at the wound site for a much shorter period of time (Buchanan et al, 2009; Hantash et al, 2008; Kishi et al, 2012; Leavitt et al, 2016). This is interesting as it may be similar to what is observed in animals with the natural ability to regenerate, where although an immune response is necessary the length of time the immune cells stay at the site of injury is significantly shorter (Kawasumi et al, 2013; Reinke and Sorg, 2012; Seifert et al, 2012b; Takeo et al, 2015; Walmsley et al, 2015; Wilgus, 2007; Godwin et al, 2013; Godwin and Rosenthal, 2014).…”

Preparation of Amniotic Membrane and It’s Application in the Treatment of Skin Loss and Lyell's Syndrome (Toxic Epidermal Necrolysis): Current State and New Opportunities

“…These promising results show that the capability to induce death of cancer calls and antiangiogentic properties of the amniotic membrane are maintained even after cryopreservation [37]. Another promising feature of the amniotic membrane is its ability to reduce the formation of scar tissue -as a fetal tissue it significantly minimizes cicatrization [38].…”