Development of Multifunctional-Sprayable Protein Hydrogels as an Antiadhesive Barrier for Postoperative Tissue Adhesions

Abstract

Postoperative tissue adhesions are among the most frequent surgical complications, occurring in 60–90% of abdominal and pelvic operations and over 90% of gynaecological procedures. These fibrous bands form between organs or tissues following surgical trauma, causing pain, infertility, bowel obstruction, and complications during repeat surgeries. Current commercial formulations, including hydrogels, have major limitations to their clinical viability such as high cost, inadequate tissue adherence, variable efficacy, low stability, low tissue anchorage, fast resorption, and uneven coverage. To combat these limitations and develop a commercially viable one-step, easy-to-use solution, we have developed a multifunctional sprayable hydrogel which can be formed in situ by mixing modified-albumin solution and a crosslinker mixture comprising of optimized concentrations of calcium ions, epigallocatechin-3-gallate (EGCG) and tetrakis(hydroxymethyl) phosphonium chloride (THPC). Upon mixing, THPC induces covalent crosslinking with albumin, while EGCG reduces THPC toxicity by scavenging formaldehyde, while uniformly entrapping stable albumin–polyphenol complexes. The hydrogel undergoes instantaneous in situ gelation, forming an adherent network that can be applied to irregular tissue surfaces by spraying or dispensing. The solutions turn turbid while gelling which is advantages for the surgeon to establish areas of coverage. When tested in vitro, hydrogels displayed good biocompatibility, antioxidant properties, minimal swelling and minimal to no cell adhesion against L929 mouse-fibroblast cells. Scratch assays revealed a decrease in cell migration and proliferation, which can be beneficial in adhesion prevention. Ex vivo porcine skin adhesion tests revealed adequate wet tissue adhesion (~17-21 kPa) after 1 hour at physiological conditions and were able to successfully seal punctured small intestine. Further testing revealed that the hydrogels resist enzymatic degradation, exhibit adequate mechanical integrity, have strong ROS scavenging ability and strong angiogenic potential, which can further aid in wound healing, in addition to its efficacy as a mechanical barrier between healing tissues. The accessible, low-cost formulation, combined with consistent performance and multifunctional biological activity, positions this hydrogel system as a strong candidate for clinical translation. It supports indigenous MedTech innovation aimed at enhancing postoperative care, benefiting both local healthcare settings and broader global applications.