Optimum healing of a cutaneous wound requires a well-orchestrated integration of the complex biological and molecular events of cell migration and proliferation, and of extracellular matrix ...deposition and remodelling. Cellular responses to inflammatory mediators, growth factors, and cytokines, and to mechanical forces, must be appropriate and precise. However, this orderly progression of the healing process is impaired in chronic wounds, including those due to diabetes. Several pathogenic abnormalities, ranging from disease-specific intrinsic flaws in blood supply, angiogenesis, and matrix turnover to extrinsic factors due to infection and continued trauma, contribute to failure to heal. Yet, despite these obstacles, there is increasing cause for optimism in the treatment of diabetic and other chronic wounds. Enhanced understanding and correction of pathogenic factors, combined with stricter adherence to standards of care and with technological breakthroughs in biological agents, is giving new hope to the problem of impaired healing.
Scar formation, with persistent alteration of the normal tissue structure, is an undesirable and significant result of both wound healing and fibrosing disorders. There are few strategies to prevent ...or to treat scarring. The transforming growth factor beta (TGF‐β) superfamily is an important mediator of tissue repair. Each TGF‐β isoform may exert a different effect on wound healing, which may be context‐dependent. In particular, TGF‐β1 may mediate fibrosis in adults’ wounds, while TGF‐β3 may promote scarless healing in the fetus and reduced scarring in adults. Thus, TGF‐β3 may offer a scar‐reducing therapy for acute and chronic wounds and fibrosing disorders.
Abstract Treatment of chronic wounds remains difficult, in spite of better understanding of pathophysiologic principles and greater adherence to recognized standards of care. Even with recent ...advances stemming from breakthroughs in recombinant growth factors and bioengineered skin, up to almost 50% of chronic wounds that have been present for more than a year remain resistant to treatment. Because of these realities, there is excitement in the use of stem cells to offset impaired healing. Early data appear encouraging, but much work remains to be done. Although pilot studies suggest that multipotent adult stem cells can accelerate wound repair or even reconstitute the wound bed, the answers will need to come from randomized clinical trials. Thus far, considerable focus has been placed on bone marrow–derived mesenchymal stem cells, and there are now promising approaches for introducing them into the wound. It might turn out, however, that other types of stem cells will be more effective, including those derived from hair follicles or, perhaps, subsets of bone marrow–derived cultured cells. Still, proper wound care and adherence to basic principles cannot be bypassed, even by the most sophisticated approaches.
The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound ...healing slows with age. However, the basic biology underlying chronic wounds and the influence of age‐associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi‐morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age‐associated changes in chronic wound healing.
The science of wound bed preparation Panuncialman, Jaymie; Falanga, Vincent
The Surgical clinics of North America,
06/2009, Letnik:
89, Številka:
3
Journal Article
Recenzirano
The concept of wound bed preparation (WBP) heralded a new era in terms of how we treat wounds. It emphasized the difference between acute and chronic wounds, and it cemented the idea that the ...processes involved in the healing of acute wounds do not apply completely to the healing of chronic wounds. The arbitrary division of the normal healing process into the phases of hemostasis, inflammation, proliferation, and maturation addresses the events in acute wound healing. We have realized that the impediments to healing in chronic wounds lead to a failure to progress through these phases and are independent factors that make the chronic wound a much more complex condition. A major advance in resolving or addressing the chronic wound has been the concept of WBP. WBP allows us to address the problems of wound healing individually the presence of necrotic tissue, hypoxia, high bacterial burden, corrupt matrix, and senescent cells within the wound bed. In WBP we can optimize our therapeutic agents to accelerate endogenous healing or to increase the effectiveness of advanced therapies.
The efficacy of a bilayered, living skin construct (APLIGRAF®Graftskin) was evaluated in patients (n = 120) with hard‐ to‐heal venous leg ulcers of greater than 1 year's duration. The study was ...prospective, randomized, and controlled. Patients received Graftskin plus compression therapy, or standard compression therapy (active control). Patients were evaluated for frequency and time to complete (100%) wound closure. Treatment with Graftskin was significantly more effective than active control in the percentage of patients healed by 6 months (47% vs. 19%; p < 0.005) and the median time to complete wound closure (p < 0.005). Analysis with multivariate regression methods, adjusting for factors generally thought to influence wound healing (duration, baseline area, depth, location, fibrinous wound bed, and infection), showed that patients treated with Graftskin were twice as likely to achieve complete wound closure by 6 months (p < 0.005), and over 60% more effective in achieving wound closure than active control (p < 0.01). These data indicate that Graftskin is an effective treatment for venous ulcers of greater than 1 year's duration.
Animal models have been developed to study the complex cellular and biochemical processes of wound repair and to evaluate the efficacy and safety of potential therapeutic agents. Several factors can ...influence wound healing. These include aging, infection, medications, nutrition, obesity, diabetes, venous insufficiency, and peripheral arterial disease. Lack of optimal preclinical models that are capable of properly recapitulating human wounds remains a significant translational challenge. Animal models should strive for reproducibility, quantitative interpretation, clinical relevance, and successful translation into clinical use. In this concise review, we discuss animal models used in wound experiments including mouse, rat, rabbit, pig, and zebrafish, with a special emphasis on impaired wound healing models.
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