Zein-based polysaccharide-tannic acid films as multifunctional barriers to prevent post-surgical adhesions

Formation of postoperative adhesions remains a significant clinical burden, frequently leading to chronic pain, bowel obstruction, and infertility. Current physical barriers have shown limited success, highlighting the need for multifunctional antiadhesive structure that combine mechanical stability with finely tuned surface properties able to act as slipping layer between adjacent organs. At this purpose polymeric zein (Z) based films doped with Chondroitin sulphated (CS) or Maltodextrin (MDx) and loaded with Tannic acid (TA) were developed and characterized by a multidisciplinary approach. The films proved to reduce muco- and bioadhesion, showed higher hydrophobicity and increased roughness that impaired conformal contact and limited adhesive interactions. Moreover, biological evaluation was performed towards Caco-2 epithelial cells, representing the luminal interface of the abdominal cavity, and NHDF fibroblasts, representing the stromal/serosal side. Proliferation assays and cell morphology confirmed the higher biocompatibility of CS- and MDX-doped films compared with the undoped ones (Z-TA1%), suggesting that polysaccharide presence not only maintain the antiadhesive properties but also enhance the biological performance by providing a hydrophilic and bioactive interface. The in vivo biocompatibility and the haemoglobin release were also performed on a murine model to highlight the biological safety of the films. This work provides mechanistic insights into how film composition governs antiadhesion and cytocompatibility, offering a rational framework for designing next-generation coatings to prevent postoperative adhesions.