Many techniques for management of hypertrophic scars and keloids have been proven through extensive use, but few have been supported by prospective studies with adequate control groups. Several new therapies showed good results in small-scale trials, but these have not been repeated in larger trials with long-term follow-up. This article reports a qualitative overview of the available clinical literature by an international panel of experts using standard methods of appraisal. The article provides evidence-based recommendations on prevention and treatment of abnormal scarring and, where studies are insufficient, consensus on best practice. The recommendations focus on the management of hypertrophic scars and keloids, and are internationally applicable in a range of clinical situations. These recommendations support a move to a more evidence-based approach in scar management. This approach highlights a primary role for silicone gel sheeting and intralesional corticosteroids in the management of a wide variety of abnormal scars. The authors concluded that these are the only treatments for which sufficient evidence exists to make evidence-based recommendations. A number of other therapies that are in common use have achieved acceptance by the authors as standard practice. However, it is highly desirable that many standard practices and new emerging therapies undergo large-scale studies with long-term follow-up before being recommended conclusively as alternative therapies for scar management.

The role of polypeptide growth factors in the processes of inflammation and repair was investigated by analyzing the influence of transforming growth factor-beta (TGF-beta), applied directly to linear incisions made through rat dorsal skin. A dose-dependent, direct stimulatory effect of a single application of TGF-beta on the breaking strength of healing incisional wounds was demonstrated. An increase in maximum wound strength of 220 percent of control was observed at 5 days; the healing rate was accelerated by approximately 3 days for at least 14 days after production of the wound and application of TGF-beta. These increases in wound strength were accompanied by an increased influx of mononuclear cells and fibroblasts and by marked increases in collagen deposition at the site of application of TGF-beta. TGF-beta is thus a potent pharmacologic agent that can accelerate wound healing in rats.

Most chronic wounds can be classified into three major types: pressure ulcers, venous ulcers, and diabetic ulcers. The authors propose a unifying hypothesis of chronic wound pathogenesis based on four main causative factors: local tissue hypoxia, bacterial colonization of the wound, repetitive ischemia-reperfusion injury, and an altered cellular and systemic stress response in the aged patient. Traditional strategies for the treatment of chronic wounds have shown limited success. The authors explore potential treatment regimens specifically aimed at each individual determinant of chronic wound pathogenesis. Furthermore, they explore a combined therapeutic approach that collectively targets all the components of chronic wound pathology. These innovative ideas and therapies could be of substantial interest for clinicians and researchers, while further offering significant benefit to patients with chronic wounds.

Abstract. This article provides an overview of the role of oxygen in wound healing. The understanding of this role has undergone a major evolution from its long-recognized importance as an essential factor for oxidative metabolism, to its recognition as an important cell signal interacting with growth factors and other signals to regulate signal transduction pathways. Our laboratory has been engaged in thestudy of animal models of skin ischemia to explore in vivo the impact of hypoxia as well as the use of oxygen as a therapeutic agent either alone or in combination with other agents such as growth factors. We have demonstrated a synergistic effect of systemic hyperbaric oxygen and growth factors that has been substantiated by Hunt's group. Within the past 10 years research in the field of wound healing has given new insight into the mechanism of action of hypoxia and hyperoxia as modifiers of the normal time-course of wound healing. The article concludes with a discussion of why hypoxia and hyperoxia intercurrently play an important role in wound healing. Hypoxia-inducible factor 1 is crucial in that interplay.

Abstract. Platelet-derived growth factor (PDGF) and transforming growth factor-~ (TGF-/~) markedly potentiate tissue repair in vivo. In the present experiments, both in vitro and in vivo responses to PDGF and TGF-B were tested to identify mechanisms whereby these growth factors might each enhance the woundhealing response. Recombinant human PDGF B-chain homodimers (PDGF-BB) and TGF-B1 had identical dose-response curves in chemotactic assays with monocytes and fibroblasts as the natural proteins from platelets. Single applications of PDGF-BB (2 #g, 80 pmol) and TGF-B1 (20 #g, 600 pmol) were next applied to linear incisions in rats and each enhanced the strength required to disrupt the wounds at 5 d up to 212% of paired control wounds. Histological analysis of treated wounds demonstrated an in vivo chemotactic response of macrophages and fibroblasts to both PDGF-BB and to TGF-/~ 1 but the response to TGF-B1 was significantly less than that observed with PDGF-