PDE5A and diabetes mellitus: The in vitro and in vivo effects of NO donors and PDE5-Is on the different cell types involved in wound repair, as well as the potential additive effect of NO supplementation and PDE5 inhibition, were not tested until Greenwald et al. reported the synthesis of TOP-N53 (60), a dual-acting NO donor and PDE5 inhibitor, having wound healing effects in both normal mice and mice with diabetes mellitus [271].