Muhammad Akmal, Sadia Iqbal, Seung‐Wook Kim, Dae‐Yong Jeong, Fauzia Iqbal, Atia Iqbal, Zahoor H. Farooqi
A robust interpenetrating polymer network (IPN) hydrogel comprising Poly(acrylamide)-Poly(vinyl alcohol) (P(AM)/PVA) was engineered via UV-induced photopolymerization to achieve multifaceted enhancements in mechanical integrity, antimicrobial efficacy and cytocompatibility. The P(AM)/PVA hydrogel exhibited a highly interconnected porous microstructure (90% porosity), a crosslink density of 36.04 mol·m −3 , exceptional water retention capacity and a compressive modulus of 6.75 MPa, aligning with the mechanical demands of soft to semi-rigid tissue scaffolds. Functional enhancement with silver nanoparticles (Ag-NPs) introduced localized nanoscale reinforcement, increasing the compressive strength to 7.35 MPa and elevating the crosslink density to 55.60 mol·m −3 via physical entrapment and secondary interactions. In contrast, incorporation of Fe³⁺ ions facilitated supramolecular ionic crosslinking and coordination complexation within the hydrogel matrix, drastically enhancing network stiffness (16.50 MPa) and densification (76.97 mol·m −3 ), while concurrently reducing porosity through collapse of hydration domains. Antibacterial profiling revealed superior inhibition zones for Fe³⁺-modified hydrogels, attributed to in situ generation of hydroxyl radicals via Fenton-driven redox catalysis. Cytocompatibility assays demonstrated high metabolic activity in pure and Ag-NP-infused constructs, while Fe³⁺-functionalized samples elicited mild cytotoxic responses, potentially linked to microenvironmental acidification and redox-induced oxidative stress. This multifunctional hydrogel system offers a synergistic interplay between mechanical reinforcement, antimicrobial action and cellular permissiveness, positioning it as a promising extracellular matrix analog for regenerative engineering, particularly in osteogenic and load-bearing tissue contexts.