Scarless Fetal Wound Healing: A Basic Science Review

Abstract

Summary Scar formation is a major medical problem that can have devastating consequences for patients. The adverse physiological and psychological effects of scars are broad, and there are currently no reliable treatments to prevent scarring. In contrast to adult wounds, early gestation fetal skin wounds repair rapidly and in the absence of scar formation. Despite extensive investigation, the exact mechanisms of scarless fetal wound healing remain largely unknown. For some time, it has been known that significant differences exist among the extracellular matrix, inflammatory response, cellular mediators, and gene expression profiles of fetal and postnatal wounds. These differences may have important implications in scarless wound repair.

Scar Management in the Pediatric and Adolescent Populations

“…100 Elucidating these fundamental mechanisms of wound repair promises to inform future therapeutic modalities, and perhaps even reintroduce scarless healing. 101,102 …”

Chemokines in Wound Healing and as Potential Therapeutic Targets for Reducing Cutaneous Scarring

“…1 Fetal wound healing is entirely regenerative before 24 weeks gestation, without scar tissue formation. 2,3 Behavioral discrepancies have been attributed to differing inflammatory responses and cytokine profiles of fetal and adult wounds. These are controlled by a range of bioactive molecules, including chemokines.…”

“…Over 50 chemokines have been identified to date, divided into 4 subgroups based on the arrangement of the first 2 of the 4 cysteine amino acids -CC, CXC, CX 3 C, and C 19 ( Fig. 1).…”

miRNA Control of Tissue Repair and Regeneration

“…71 Scarless regenerative healing is an intrinsic property of the fetal skin. 72 Major differences in the ECM of the fetal and the adult skin account for the sharp contrast in healing phenotype between the fetus and adult skin. 73 Fetal skin ECM predominantly expresses type III collagen, elevated hyaluronic acid, and elevated matrix metalloproteinase to tissue-derived inhibitor (MMP:TIMP) ratio that facilitates cell movements, turnover of ECM modulators, and tissue remodeling.…”

“…73 Fetal skin ECM predominantly expresses type III collagen, elevated hyaluronic acid, and elevated matrix metalloproteinase to tissue-derived inhibitor (MMP:TIMP) ratio that facilitates cell movements, turnover of ECM modulators, and tissue remodeling. 72,74 One of the hallmarks of fetal skin development is the lower abundance of miRNAs caused by mechanisms that are aimed at silencing PTGS during tissue development, enabling expression of otherwise silenced coding genes that drive skin development. Of such miRNAs that are silenced during fetal development, low abundance of miR-29 was reported in skin across several species.…”