Poor skin healing (e.g., due to diabetes, obesity, pressure wounds) is a condition affecting over 6 million patients in the USA alone. In response to the improper healing, fibrotic tissue develops. Notably, fibrosis can affect virtually all tissues and is estimated to be associated with 45% of deaths in the western world. Despite this huge impact on society and related economic burden, treatments that prevent fibrosis progression are unavailable, and current treatments slightly slow its progression but do not treat the underlying causes. Employing lessons from basic research carried out in our labs, we have identified peptides derived from the extracellular matrix (ECM) glycoprotein fibronectin that when added to cultured cells inhibit ECM deposition and organization, reduce cell adhesion, and inhibit fibroblast-to-myofibroblast transition, processes at the basis of fibrosis. Notably, upon administration to excision wounds in mouse skin, these inhibiting peptides reduced the size of the fibrotic lesions and promoted skin regeneration. Here we propose to identify the inhibiting peptides’ in vivo half-life and penetration depth, and test whether they can inhibit the fibrotic behaviors of fibroblasts derived from patients with fibrotic skin diseases. While this proposal is aimed at dissecting the inhibiting peptides’ activity on skin wound healing, the peptides and the underlying mode of action are conserved in all fibrotic diseases. Hence, this work will not only allow us to develop a treatment for skin lesions, but importantly, will also pave the way towards the development of a pan-anti-fibrosis drug – a treatment which at present does not exist.