Development of clay/alginate/chondroitin sulfate composite microspheres via continuous process for chronic wounds regeneration

• Spray-dried alginate/chondroitin sulfate-based microparticles were produced and crosslinked. • ZnAl LDH were doped into the microparticles for enhanced wound healing. • Green and continuous techniques were used for LDH and microparticles production. • The LDH doping increased the stability, allowed the release of Zn as bioactive ion. • In vitro and in vivo studies suggested the safety and efficacy of the systems. Chronic wounds significantly affect the quality of life of millions of people, generating substantial problems for the patients and for health care systems. Therefore, this work focuses on the development of microparticles based on alginate and chondroitin sulfate which were doped with layered double hydroxides (LDH), anionic clay minerals, based on Zn and Al. The obtained clay/polysaccharide composite materials could provide enhanced properties for wound healing, in particular related to cell adhesion and proliferation. The microparticles were manufactured by spray drying and crosslinked using CaCl 2 to obtain insoluble scaffolds for application in the physiological environment. The materials and the process were chosen continuous manufacturing in the industrial field. The mean diameter of the obtained microparticles ranged from 10 to 15 µm with a narrow dimensional distribution. Solid state characterizations (XRD, FTIR, SAXS, TGA/DSC) confirmed the LDH doping in a concentration of around 5 %w/w. The presence of LDH enhanced the stability of the systems in aqueous environment, increasing the wettability and decreasing the zeta potential due to their positive charge. Preclinical in vitro studies suggested a positive impact of LDH doping which led to a cell proliferation increase of around 15 %. In vivo studies demonstrated the safety and efficacy of the systems, suggesting the potential of this platform for therapeutic use.