Epidermal T cells have been shown to play unique roles in tissue homeostasis and repair in mice through local secretion of distinct growth factors in the skin. Human epidermis contains both αβ+ and γδ+ T cells whose functional capabilities are not understood. We demonstrate that human epidermal T cells are able to produce insulin-like growth factor 1 (IGF-1) upon activation and promote wound healing in a skin organ culture model. Moreover, an analysis of the functional capabilities of T cells isolated from acute versus chronic wounds revealed a striking difference. Both αβ+ and Vδ1+ T cells isolated from acute wounds actively produced IGF-1, demonstrating that they are activated during tissue damage to participate in wound repair. In contrast, IGF-1 production could not be detected in T cells isolated from chronic wounds. In fact, skin T cells isolated from chronic wounds were refractory to further stimulation, suggesting an unresponsive state. Collectively, these results define a novel role for human epidermis–resident T cells in wound healing and provide new insight into our understanding of chronic wound persistence.

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Keloids and hypertrophic scars are significant symptomatic clinical problems characterized by excess collagen. Although extensive research has focused on fibroblasts and collagen turnover in these aberrant scars, little work has been done on the expression of integrins (cell membrane structures that link cells to extracellular matrix) within these lesions. Integrin-mediated regulation of collagen synthesis has previously been observed in explanted fibroblasts from normal and fibrotic dermis, and integrin alpha1 knockout mice maintain increased collagen synthesis consistent with a role for alpha1beta1 in providing negative feedback on collagen synthesis. These findings suggested the need to evaluate integrin roles in keloids and hypertrophic scars. In this study we examined integrin expression in keloids (n = 11), hypertrophic scars (n = 5), radiation ulcers (n = 2), and normal skin specimens (n = 8). We used a novel approach to analysis by isolating dermal fibroblasts directly from tissue (without explant culture) and determining surface integrin expression by flow cytometry. We found that keloids and hypertrophic scars have marked alterations in fibroblast integrin expression and contain several distinct populations of fibroblasts. One of these populations expresses high levels of alpha1 integrin, and the proportion of these cells is higher in keloids (63% +/- 3.6% SEM) and hypertrophic scars (45% +/- 2.7% SEM) than in normal skin tissues (28% +/- 4.7% SEM). The different populations of fibroblasts defined by integrin expression merge, however, when the cells are serially cultured, suggesting that there may be aspects of the dermal microenvironment that maintain the integrin phenotypic heterogeneity in dermal fibroblasts.

Wound management encompasses a number of disciplines. As new concepts and innovative technologies develop within this exciting field, it is important to share them in spite of the divergence of clinical perspectives between the expert disciplines. One such divergence exists between surgeons and nonsurgical wound specialists. As a result, there is a need to develop a common language between these two groups. How can we develop a common language that unites surgical expertise within medical wound management? One route may be through the principles of wound bed preparation, which we believe have great potential for the communication of effective surgical techniques. Another is through sharing our concepts of surgical debridement as it is applied to different wounds by a variety of surgical disciplines. In this monograph, we try to bring these two themes together. We discuss how wound bed preparation has added to our understanding of the pathophysiology of the nonhealing wound and has provided us with some general clinical concepts. We discuss what role debridement, and then specifically surgical debridement, has to play within wound bed preparation, before analyzing the importance of surgical debridement in tissue preservation and the control of infection. We finally look at ongoing work that examines the cost of various surgical debridement techniques. We will also review a new hydrosurgery system (VERSAJET, Smith and Nephew, Hull, UK), which we believe has an important role to play in the surgical preparation of the wound. We also expect that this paper will remind our medical colleagues about the critical role played by surgery in wound management.

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Cerebral palsy (CP), caused by an injury to the developing brain, can lead to alterations in muscle function. Subsequently, increased muscle stiffness and decreased joint range of motion are often seen in patients with CP. We examined mechanical and biochemical properties of the gastrocnemius and soleus muscles, which are involved in equinus muscle contracture. Passive mechanical testing of single muscle fibers from gastrocnemius and soleus muscle of patients with CP undergoing surgery for equinus deformity showed a significant increase in fiber stiffness (p < 0.01). Bundles of fibers that included their surrounding connective tissues showed no stiffness difference (p ¼ 0.28).). When in vivo sarcomere lengths were measured and fiber and bundle stiffness compared at these lengths, both fibers and bundles of patients with CP were predicted to be much stiffer in vivo compared to typically developing (TD) individuals. Interestingly, differences in fiber and bundle stiffness were not explained by typical biochemical measures such as titin molecular weight (a giant protein thought to impact fiber stiffness) or collagen content (a proxy for extracellular matrix amount). We suggest that the passive mechanical properties of fibers and bundles are thus poorly understood. ß

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