Final Report Summary - WOUND CONTRACTION (Keratinocytes and Matrix metalloproteinases: driving force of skin wound contraction?) When skin wounds fail to heal normally, chronic non-healing wounds or excessive scars are the result. In order to provide effective treatments, a profound understanding of wound healing processes is needed. Matrix metalloproteinases (MMP) are enzymes that contribute to normal wound healing by facilitating cell migration and scar remodelling. In case of increased presence of specific MMPs, wound repair can be hampered. Without MMPs, skin wounds do not heal.The ERC Starting Grant project consisted of two parts. In the first sub-project, the effect of a specific member of the MMP family, e.g. MMP-3, was investigated. We could show for the first time that MMP-3 contributed to increased collagen degradation during inflammation in cutaneous wound healing. This could be blocked by a specific MMP-3 inhibitor. Thus, MMP-3 contributes to excessive collagen destruction during highly inflammatory conditions in skin wounds. In normal skin wound repair, MMP-3 is involved in wound contraction. Wounds without MMP-3 contract more slowly than normal wounds whereas wounds with excess MMP-3 contract faster. The balance between the best MMP-3 concentration and most effective wound closure has yet to be determined. In highly inflammatory conditions, specific MMP-3 inhibitors could be beneficial to prevent excessive skin tissue destruction followed by defective or impaired wound closure. In the second sub-part of the project, the effect of lung surfactants on skin wound healing was investigated. Lung surfactants are used clinically in preterm born infants for lung maturation to ease breathing. This extraordinary idea originated from the hypothesis that skin cells might behave like lung cells at the air-liquid-interphase. As a consequence, surface modulation by lung surfactant might lead to better skin wound healing. Indeed, topical application of lung surfactant to skin tissue and skin wounds showed a reduction of inflammation and better scarring in comparison to standard clinical therapy with fatty gauze. These overwhelming results led to the approval for financial funding by yet another ERC grant, the ERC Proof-of-Concept Grant SUMOWO. In this study, evidence for the safety and applicability of this novel treatment should be provided to establish a new treatment modality for skin wound repair in humans.
