Porous Functionally Graded Scaffold prepared by a single-step freeze-drying process. A bioinspired approach for wound care.

[Display omitted] • Development of a porous three-layered Functionally Graded Scaffold (FGS) based on κ-carrageenan for wound management. • Design and preparation of three FGS layers by exploiting κ-carrageenan interactions with multifunctional agents, such as arginine and whey protein isolate. • Set-up of a single-step freeze-drying process for FGS preparation. • FGS layers are characterized by different pore size, water content capability and mechanical properties, mimicking the structure of native skin tissue. • In vitro studies (fibroblast cell line) demonstrated the excellent biocompatibility and the ability of FGS layers to act as a support for cell growth. • In vivo experiments (murine model) highlighted that FGS layers were effective in promoting wound healing. Nowadays, chronic wounds are the major cause of morbidity worldwide and the healthcare costs related to wound care are a billion-dollar issue; chronic wounds involve a non-healing process that makes necessary the application of advanced wound dressings to promote skin integrity recovery. Functionally Graded Scaffolds (FGSs) are currently driving interest as promising candidates in mimicking the skin tissue environment and, thus, in enhancing a faster and more effective wound healing process. Aim of the present work was to design and develop a porous FGS based on κ-carrageenan (κCG) for the management of chronic skin wounds; a freeze-drying process was optimized to obtain in a single-step a three-layered FGS characterized by a pore size gradient functional to mimic the structure of native skin tissue. In addition to κCG, arginine and whey protein isolate were used as multifunctional agents for FGS preparation; these substances can not only intervene in some stages of wound healing but are able to establish non-covalent interactions with κCG, which were responsible for the production of layers with different pore size, water content capability and mechanical properties. Cell migration, adhesion and proliferation within the FGS structure were evaluated in vitro on fibroblasts and FGS wound healing potential was also studied in vivo on a murine model. [ABSTRACT FROM AUTHOR]