clinical case reconstructed by Guido Majno (1975) from the Hippocratic records describes a wrestler who visits the iatreion (out-patient clinic) to be treated for a shoulder dislocation. With less invasive procedures no longer working to tighten the dislocation, the clinic adopts the drastic measure of inducing wound contraction by poking a hot needle through the skin of the armpit, and \"in this way the cavity, into which the humerous is mostly displaced, is best scarred over and cut off\" In Greek medicine circa 400 B.C.E., familiarity with wound contraction after burn injury already was commonplace. Closure of cutaneous wounds involves three processes: epithelization, connective tissue deposition, and contraction. The contribution of each process varies according to the type of wound. In general, epithelization results in resurfacing of the wound; connective tissue deposition results in replacement of damaged dermis; and contraction brings the margins of open wounds together (Peacock, 1984; Clark, 1988; Mast, 1992). In mammals with loose skin (meaning loosely attached to the underlying tissue layer), wound contraction leads to wound closure with little scarring or loss of function. In humans, whose skin is more firmly attached to underlying tissues, the consequences of contraction are less beneficial, ranging from minimal cosmetic scar in some cases to loss of joint motion or major body deformation in others. Consequently, a distinction has been made between contraction as a normal process of wound closure, and contracture as the abnormal result of the contraction process where signifcant scarring or loss of function occurs (Hunt and Dunphy, 1979). The pathologic consequences of tissue contraction include a variety of conditions ranging from contracture of the fibrous capsule surrounding breast implants to constricture of hollow organs (e.g., the esophagus) after injury (Skalli and Gabbiani, 1988; Rudolph et al., 1992). In contemporary cell biology, research on wound contraction focuses on the wound fibroblast. Skin fibroblasts normally are sessile and quiescent, but shortly after cutaneous wounding, they become activated. Activated fibroblasts migrate to the fibronectin-fibrin wound interface, proliferate, and synthesize a new collagen-containing matrix called granulation tissue. Around the same time, wound contraction begins. Once the wound defect is replaced, the expanded fibroblast population stops dividing and regresses and extracellular matrix remodeling commences (Peacock, 1984; Clark, 1993). Despite the importance of wound contraction for wound

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Fibroblasts, myofibroblasts, and wound contraction

Excessive scars form as a result of aberrations of physiologic wound healing and may arise following any Insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patient’s quality of life, both physically and psychologically. Multiple studies on hypertrophic scar and keloid formation have been conducted for decades and have led to a plethora of therapeutic strategies to prevent or attenuate excessive scar formation. However, most therapeutic approaches remain clinically unsatisfactory, most likely owing to poor understanding of the complex mechanisms underlying the processes of scarring and wound contraction. In this review we summarize the current understanding of the pathophysiology underlying keloid and hypertrophic scar formation and discuss established treatments and novel therapeutic strategies.

Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies

Zinc requirements and the risks and benefits of zinc supplementation

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.

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

On the Nature of Hypertrophic Scars and Keloids: A Review Frank Niessen;Paul Spauwen;Joost Schalkwijk;Moshe Kon; Plastic and Reconstructive Surgery

M. Dobrkovsky

Papers

The Histiotypic Organization of the Hypertrophic Scar in Humans

Techniques for decreasing scar formation and contractures in the burned patient.

Contracture and Scar Formation in the Burn Patient

Ultrastructural analysis of pressure-treated human hypertrophic scars.

Zinc deficiency in burned children.