Two unconventional concepts of skin contraction are presented that could change the current paradigm of wound healing. The overall objective is to clarify the underlying processes and to develop new therapies to prevent excessive scarring, ameliorate patients lives and reduce medical health care expenses. Specific emphasis lies on the role of Matrix metalloproteinases (MMP) and keratinocytes. Previous internationally acknowledged work of the PI resulted in these challenging concepts. The project will take place at the Medical School Hannover with its vast scientific infrastructure perfectly suited for this type of pioneer research. Unconventional is the concept that MMP lead to contrary cell responses. By degrading matrix molecules, MMP induce cell disassembly and migration. Only MMP-3 and -7 cleave cadherins and induce adhesion. MMP-3 deficient mice showed normal wound epithelialisation without contraction. Presumably by controlled proteolysis of intercellular molecules, cell adhesivity increases. Firm adhesion complexes provide stable anchorage sites for force generation. Selective MMP-3 inhibition would reduce contraction without impairing epithelialisation. The concept of the epithelial role in contraction differs from the paradigm and marks a beyond the state-of-art approach in wound healing. Keratinocytes at the air-liquid interphase close wounds by reepithelialisation and surface minimization. Hence, reduction of surface tension would decrease epidermal contraction. Alveolar surface tension is reduced by surfactants in preterm infants. Assuming that epidermal wounds could profit of surfactants is a high risk high gain approach of tackling hypertrophic scarring, but if successful it would revolutionize burn wound therapy.
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