Hydrogels from Wharton's jelly as alternative to conventional extracellular matrix-based constructs

Extracellular matrix (ECM)-based hydrogels are increasingly used in regenerative medicine; however, animal-derived sources such as rat tail tendon ECM (RT-ECM)-the current gold standard-face limitations for clinical translation. We propose hydrogels derived from decellularized human Wharton's jelly (WJ-ECM) as a bioactive and sustainable alternative. Compared to RT-ECM, WJ-ECM hydrogels exhibit a distinct biochemical composition, combining type I/III collagen and glycosaminoglycans, and form thinner fibrils. Upon exposure to culture medium, they display reduced syneresis. Rheological and confined compression tests reveal lower stiffness and decreased permeability. Functionally, WJ-ECM hydrogels demonstrate superior hemostatic properties, reduce intracellular ROS accumulation in neutrophils, and promote an anti-inflammatory phenotype in macrophages. In vivo implantation confirms their biocompatibility with minimal adverse effects. These results highlight the potential of WJ-ECM hydrogels as a clinically relevant biomaterial for regenerative medicine and cell culture applications.