Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Abstract

Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation.

Figures

Christopher J. Jackson, PhD

Figure 1.

The three classic stages of cutaneous wound healing. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 2.

Major extracellular matrix components and their interactions with each other and cell membrane. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 3.

The process of collagen assembly to form collagen fiber. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Figure 4.

The production of TGF-β1 and TGF-β3 by human keratinocytes treated with APC. Keratinocyte monolayers were treated with APC (1 μg/mL). Culture supernatants were collected at for day 1, 2, 3, and 5 after treatment. TGF-β1 and TGF-β3 in supernatants were detected by enzyme-linked immunosorbent assay. Data are expressed as mean±standard error of the mean from four experiments. APC, activated protein C; TGF, transforming growth factor. *p<0.05, **p<0.01.