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Epithelial to mesenchymal transition (EMT) is a process whereby epithelial cells undergo transition to a mesenchymal phenotype and contribute directly to fibrotic disease. Recent studies support a role for EMT in cutaneous fibrotic diseases including scleroderma and hypertrophic scarring, although there is limited data on the cytokines and signalling mechanisms regulating cutaneous EMT. We investigated the ability of TGF-β and TNF-α, both overexpressed in cutaneous scleroderma and central mediators of EMT in other epithelial cell types, to induce EMT in primary keratinocytes and studied the signalling mechanisms regulating this process. TGF-β induced EMT in normal human epidermal keratinocytes (NHEK cells), and this process was enhanced by TNF-α. EMT was characterised by changes in morphology, proteome (down-regulation of E-cadherin and Zo-1 and up-regulation of vimentin and fibronectin), MMP secretion and COL1α1 mRNA expression. TGF-β and TNF-α in combination activated SMAD and p38 signalling in NHEK cells. P38 inhibition with SB203580 partially attenuated EMT, whereas SMAD inhibition using SB431542 significantly inhibited EMT and also reversed established EMT. These data highlight the retained plasticity of adult keratinocytes and support further studies of EMT in clinically relevant in vivo models of cutaneous fibrosis and investigation of SMAD inhibition as a potential therapeutic intervention.

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The aim of this study was to investigate the role of a completely synthetic dermal matrix (Biodegradable Temporising Matrix) for staged reconstruction of complex wounds. The authors defined complex wounds as wounds not amenable to reconstruction with skin grafting alone due to an inherent avascularity such as the presence of bare bone, tendinous or neural structures. A retrospective review of a prospectively maintained database of complex wounds as defined above was carried out. 55 patients were identified who underwent staged Biodegradable Temporising Matrix and autologous skin graft reconstruction for complex wounds affecting a wide variety of patient demographics, treatment indications and body sites. Wound aetiology included burn injury and non-burn related trauma such as degloving injury or infective complications. Caveats relating to successful application of staged dermal matrix reconstruction, techniques, tips, prevention and management of complications are outlined. This large consecutive case series, demonstrates the integral role dermal substitutes play in providing biological wound cover for avascular wound beds which may otherwise require complex distant flap or free tissue transfer for reconstruction. Staged synthetic dermal matrix reconstruction has proven robustness in the face of unfavourable wounds compared with non-synthetic dermal matrices, physiologically covering avascular structures, allowing for early graft take, expediting rehabilitation and mobilisation with good scar cosmesis and limited contracture formation.

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