The skin is the biggest organ of the human being and has many functions. Therefore, the healing of a skin wound displays an extraordinary mechanism of cascading cellular functions which is unique in nature. As healing and regeneration processes take place in all parts of the human body, this review focuses on the healing processes of the skin and highlights the classical wound healing phases. While regeneration describes the specific substitution of the tissue, i.e. the superficial epidermis, mucosa or fetal skin, skin repair displays an unspecific form of healing in which the wound heals by fibrosis and scar formation. The first stage of acute wound healing is dedicated to hemostasis and the formation of a provisional wound matrix, which occurs immediately after injury and is completed after some hours. Furthermore, this phase initiates the inflammatory process. The inflammatory phase of the wound healing cascade gets activated during the coagulation phase and can roughly be divided into an early phase with neutrophil recruitment and a late phase with the appearance and transformation of monocytes. In the phase of proliferation the main focus of the healing process lies in the recovering of the wound surface, the formation of granulation tissue and the restoration of the vascular network. Therefore, next to the immigration of local fibroblasts along the fibrin network and the beginning of reepithelialization from the wound edges, neovascularization and angiogenesis get activated by capillary sprouting. The formation of granulation tissue stops through apoptosis of the cells, characterizing a mature wound as avascular as well as acellular. During the maturation of the wound the components of the extracellular matrix undergo certain changes. The physiological endpoint of mammalian wound repair displays the formation of a scar, which is directly linked to the extent of the inflammatory process throughout wound healing.

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Wound Repair and Regeneration

Since the first true herniorrhaphy was performed by Bassini over 100 years ago, all modifications and surgical techniques have shared a common disadvantage: suture line tension. The anatomic, physiologic, and pathologic characteristics of hernia recurrence are examined. The prime etiologic factor behind most herniorrhaphy failures is the suturing together, under tension, of structures that are not normally in apposition. With the use of modern mesh prosthetics, it is now possible to repair all hernias without distortion of the normal anatomy and with no suture line tension. The technique is simple, rapid, less painful, and effective, allowing prompt resumption of unrestricted physical activity.

The tension-free hernioplasty

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

(First of Two Parts) COLLAGEN is the major macromolecule of most connective tissues, and it is widely believed that many human diseases, particularly chronic diseases, will be found to involve this protein either directly or indirectly. Since collagen biosynthesis was last reviewed in the Journal in 1972,1 much new information has been gained about the relatively complex pathway by which it is synthesized. We should like to consider this new information and some of its consequences in terms of the following questions: What is the structural information in the collagen molecule, and how does it determine the structure of the . . .

Erle E. Peacock

Papers

Biologic basis for the treatment of keloids and hypertrophic scars.

Studies on the biology of collagen during wound healing. 3. Dynamic metabolism of scar collagen and remodeling of dermal wounds.

Biologic basis for the treatment of keloids and hypertrophic scars

Biological principles in the healing of long tendons.

Wound contraction and scar contracture.