Effect of Rho-Associated Protein Kinase Inhibitors on Epidermal Keratinocytes: A Proposed Application for Burn Wound...

Rho-associated protein kinases (ROCKs) affect a variety of cellular functions, including cell attachment, migration, and proliferation. ROCK inhibitors therefore have potential as tools for optimizing cell behavior in tissue engineering applications, including the manufacturing of cultivated epithelial autografts (CEAs) used in the treatment of burn patients. For example, ROCK inhibitors may facilitate earlier engraftment of CEA sheets by increasing the proliferation of skin keratinocytes ex vivo. Nevertheless, the current understanding of ROCK inhibitor action on epidermal keratinocytes is unclear owing to multiple drug formulations, drug concentrations, and cellular function assays having been used. The aim of this review article therefore is to identify consistent patterns of ROCK inhibitor action on human keratinocytes, as well as revealing key knowledge gaps. In doing so, we propose a clearer course of action for pursuing the potential benefits of ROCK inhibitors for the future treatment of burn patients. Impact statement The properties of Rho-associated protein kinase (ROCK) inhibitors are already used clinically within the fields of cardiology, neurology, and ophthalmology. These results encourage the broadening of ROCK inhibitor uses for other clinical applications. With respect to burn patients, ROCK inhibitors may facilitate improvements in patient survival and healing by reducing the time required for generating cultivated epithelial autograft (CEA) sheets from patient biopsies. Nevertheless, varying approaches to studying the effects of ROCK inhibitors on skin cells in vitro have complicated the development of improved protocols. Our review aims to clarify a diverse and growing body of literature as to the potential benefits for burn patients.