Developing electro-spun scaffolds with ideal mechanical properties for skin purposes can profit from using the Response Surface Methodology technique to define and optimize the outcome quality and required sterilization for use in vivo. This study investigated the effects of four main independent electrospinning variables for polycaprolactone nanofibers scaffold using multivariable and multi-objective optimization. It was done to determine significant parameters on responses and find optimal conditions to reach the preferred properties. Young’s modulus, elongation-at-break, and tensile strength were the responses. After obtaining appropriate models, the impact share of variables on the responses was determined using Sobol sensitivity analysis. The results showed that flow rate is the most significant parameter of elastic modulus and tensile strength responses, with 76.45 % and 41.27 % impact shares, respectively. The polymer concentration is the following significant parameter on elongation at break, tensile strength and, Young’s modulus responses with 64.35 %, 39.485 and, 14.28 % impact share, respectively. Based on the optimized results, a skin scaffold with desired mechanical properties was achieved (under solution concentration of 10 % w/v, flow rate of 2 mL/h, nuzzle-collector distance of 15 cm, and applied voltage of 20 kV). Then it was sterilized with gamma radiation of various doses (25, 40, and 55 kGy) to use in vivo. The SEM analysis indicated no significant change in fibrous morphology due to gamma irradiation at any dosage. FTIR analysis demonstrated the breakup of ester bonds due to gamma irradiation. For samples irradiated by 25 kGy, the crystallinity percentage decreased and chains crosslinking without losing the mechanical stability was dominant. The studies demonstrated that 25 kGy of gamma irradiation could improve the mechanical properties of the optimized PCL skin scaffold, which is very promising for wound healing.
