Interpenetrating polymer network hydrogels as bioactive scaffolds for tissue engineering

Tissue engineering, after decades of exciting progress and monumental breakthroughs, has yet to make a significant impact on patient health. It has become apparent that a dearth of biomaterial scaffolds that possess the material properties of human tissue while remaining bioactive and cytocompatible has been partly responsible for this lack of clinical translation. Herein, we propose the development of interpenetrating polymer network hydrogels as materials that can provide cells with an adhesive extracellular matrix-like 3D microenvironment while possessing the mechanical integrity to withstand physiological forces. These hydrogels can be synthesized from biologically-derived or synthetic polymers, the former polymer offering preservation of adhesion, degradability, and microstructure and the latter polymer offering tunability and superior mechanical properties. We review critical advances in the enhancement of mechanical strength, substrate-scale stiffness, electrical conductivity, and degradation in IPN hydrogels intended as bioactive scaffolds in the past five years. We also highlight the exciting incorporation of IPN hydrogels into state-of-the-art tissue engineering technologies, such as organ-on-a-chip and bioprinting platforms. These materials will be critical in the engineering of functional tissue for transplant, disease modeling, and drug screening.