Chronic skin wounds are commonly found in older individuals who have impaired circulation due to diabetes or are immobilized due to physical disability. Chronic wounds pose a severe burden to the health-care system and are likely to become increasingly prevalent in aging populations. Various treatment approaches exist to help the healing process, although the healed tissue does not generally recapitulate intact skin but rather forms a scar that has inferior mechanical properties and that lacks appendages such as hair or sweat glands. This article describes new experimental avenues for attempting to improve the regenerative response of skin using biophysical techniques as well as biochemical methods, in some cases by trying to harness the potential of stem cells, either endogenous to the host or provided exogenously, to regenerate the skin. These approaches primarily address the local wound environment and should likely be combined with other modalities to address regional and systemic disease, as well as social determinants of health.