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Hypertrophic scar (HTS) following thermal injury and other forms of trauma is a dermal fibroproliferative disorder that leads to considerable morbidity. Because of the lack of an ideal animal model, research is difficult. We have established an HTS model that involves transplanting human split-thickness skin graft (STSG) or full-thickness skin graft (FTSG) onto the backs of nude mice. The animals developed raised, firm, and reddish scars 2 months following transplantation. Histology and micromeasurement indicate raised, thickened engrafted skin with STSG and FTSG. In contrast, thickening was not observed with full-thickness rat skin grafts used as controls. Masson's trichrome staining demonstrates increased accumulations of collagen fibrils in the dermis in both scars grafted with STSG and FTSG. Staining cells with toludine blue and an antibody for F4/80 showed an increase in the infiltration of mast cells and macrophages. Quantification of fibrocytes reveals increased fibrocytes. Moreover, STSG grafted skin had significantly more macrophages, mast cells, and fibrocytes than FTSG. Real-time polymerase chain reaction analysis showed significantly elevated mRNA levels for type I collagen, transforming growth factor-β, connective tissue growth factor and heat shock protein 47 in both types of engrafted skin. These data demonstrate that human skin grafted onto nude mice develops red raised and thickened scars having intrinsic properties that closely resemble HTS formation as seen in humans. Interestingly, STSG developed more scar than FTSG. Furthermore, inflammatory cells and bone marrow-derived fibrocytes may play a critical role in HTS development in this animal model. [ABSTRACT FROM AUTHOR]

This study examined the mechanism of nanocrystalline silver antiinflammatory activity, and tested nanocrystalline silver for systemic antiinflammatory effects. Secondary ion mass spectroscopy of skin treated directly with nanocrystalline silver for 24 hours showed that at skin surfaces there were significant deposits at weights corresponding to Ag, AgO, AgCl, AgNO3, Ag2O, and silver clusters Ag2-6, but silver penetration was minimal. To test for translocation of the effect, a porcine contact dermatitis model in which wounds were induced on one side of the back and then treated with nanocrystalline silver on the opposite side of the back was used. Visual and histological data showed improvement relative to animals treated with saline only. Significantly increased induction of apoptosis in the inflammatory cells present in the dermis was observed with remote nanocrystalline silver treatments. In addition, immunohistochemical analysis showed decreased levels of proinflammatory cytokines tumor necrosis factor-α and interleukin-8, and increased levels of antiinflammatory cytokine interleukin-4, epidermal growth factor, keratinocyte growth factor, and keratinocyte growth factor-2. Thus, the antiinflammatory effects of nanocrystalline silver appear to be induced by interactions with cells in the top layers of the skin, which then release biological signals resulting in widespread antiinflammatory activity. [ABSTRACT FROM AUTHOR]

The development of hypertrophic scar involves a complex interplay between cells and cytokines. Although the mechanism underlying its pathogenesis is not well understood, a polarized T-helper type 2 immune response has been reported, indicating a role for CD4+ T lymphocytes in hypertrophic scarring. Here, we report an increased frequency of CD4+/transforming growth factor-β (TGF-β)-producing T cells in the peripheral blood and hypertrophic scar tissue of burn patients. These cells may play an indirect regulatory role in hypertrophic scar by affecting the functions of dermal fibroblasts. Our results show an increase in cell proliferation and collagen synthesis by dermal fibroblasts treated with medium derived from burn patient CD4+ T lymphocytes but not from the CD4+ T cells of normal subjects. Using confocal microscopy and immunoblotting, we found the level of α-smooth muscle actin to be elevated in these treated dermal fibroblasts, which also showed an enhanced ability to contract collagen lattices. TGF-β levels in medium conditioned by the culture of CD4+ T lymphocytes from burn patients were significantly higher than in the conditioned medium from CD4+ T lymphocytes of normal subjects. In addition, the application of a TGF-β–neutralizing antibody significantly reduced the effect of burn patient CD4+ T lymphocyte medium on dermal fibroblast proliferation and collagen lattice contraction. Our study suggests that CD4+/TGF-β–producing T lymphocytes may play an important role in postburn hypertrophic scarring. [ABSTRACT FROM AUTHOR]

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 remodeling. Several studies in recent years suggest that bone marrow derived stem cells such as mesenchymal stem cells, progenitor cells such as endothelial progenitor cells and fibrocytes may be involved in these processes, contributing to skin cells or releasing regulatory cytokines. Stem/progenitor cells may be mobilized to leave the bone marrow, home to injured tissues and participate in the repair and regeneration. Direct injection of bone marrow derived mesenchymal stem cells or endothelial progenitor cells into injured tissues shows improved repair through mechanisms of differentiation and/or release of paracrine factors. Enhanced understanding of these cells may help develop novel therapies for difficult cutaneous conditions such as non-healing chronic wounds and hypertrophic scarring as well as engineering cutaneous substitutes. [ABSTRACT FROM AUTHOR]