Novel therapies for scar reduction and regenerative healing of skin wounds

Fibrotic scars deposited during skin wound healing can cause disfiguration and loss of dermal function. Scar differentiation involves inputs from multiple cell types in a predictable and overlapping sequence of cellular events that includes inflammation, migration/proliferation and extracellular matrix deposition. Research into the molecular mechanisms underpinning these processes in embryonic and adult wounds has contributed to the development of a growing number of novel therapeutic approaches for improving scar appearance. This review discusses some of these emerging strategies for shifting the balance of healing from scarring to regeneration in the context of non-pathological wounds. Particular focus is given to potential therapies based on transforming growth factor (TGF)-β signaling and recent unexpected findings involving targeting of gap junctional connexins. Lessons learned in promoting scarless healing of cutaneous injuries might provide a basis for regenerative healing in other scenarios, such as spinal cord rupture or myocardial infarction.