Whey protein-chitosans complexes as sustainable and value-added biomaterials for wound healing

Chronic wounds are globally a leading cause of morbidity, and the associated healthcare costs for wound care have become a billion-dollar burden. Both natural and synthetic biomaterials, either individually or in combination, have been extensively investigated for their healing properties. The formation of protein-polysaccharide complexes through non-covalent interactions relies on the distinct physicochemical properties of the biomacromolecules involved, as well as a range of environmental factors. The present study focuses on developing sustainable, high-value biomaterials starting from food industry by-products, specifically whey protein isolate (WPI) and chitosan (CS), to be used in the design of scaffolds intended for the treatment of skin lesions. The quaternary CS derivative N,N,N-trimethyl chitosan (TMC), characterized by a high solubility in a wide pH range, was also considered. Mixtures based on CS/TMC and WPI were prepared and thoroughly characterized, considering thermal treatment, polymer MW, and pH as variables. Two different grades of CS were considered: medium (MCS) and low MW (LCS); and three different experimental conditions were analyzed: (i) denaturation of WPI alone by thermal treatment; (ii) thermal treatment of the mixture; (iii) no thermal treatment. In vitro studies were performed to assess biocompatibility and antioxidant activity of the complexes formed. To the best of our knowledge, this is the first time that complexes based on CS or TMC with WPI are produced and characterized as biomaterials intended for wound healing.