Abstract This study aimed to optimize hydrogel wound dressings to achieve favorable properties of the water vapor transmission rate (WVTR) and proper degree of swelling ratio (DSR) to overcome the issues often associated with most commercial dressings including improper breathability and insufficient exudate absorption. Artificial neural network and response surface methodologies were utilized to design and model bionanocomposites. Besides, the effect of the ratio of components as input data, and WVTR and DSR properties as output (response) data were investigated. Hydrogel systems were produced via the freeze–thaw method and were identified using infrared spectroscopy, dynamic light scattering, and scanning electron microscopy. To increase the antibacterial property of manufactured specimens, zinc oxide nanoparticles were functionalized with heparin, and, other properties including mechanical properties, in vitro wound healing as well as toxicity analysis were investigated on the optimum formulation. Results showed an improvement in mechanical properties in the presence of nanoparticles and also enhanced antibacterial property after conjugating heparin on nanoparticles. In vitro healing and cell viability results approved the biocompatibility and non-toxicity of the samples. Therefore, manufactured dressings were considered to have good DSR and WVTR, mechanical and biocompatibility properties and they exhibited good ability to heal and protect wounds.
