Highly Elastic and Tough Interpenetrating Polymer Network-Structured Hybrid Hydrogels for Cyclic Mechanical Loading-Enhanced Tissue Engineering

Although hydrogels are extensively investigated as biomaterials due to their ability to mimic cellular microenvironments, they are often limited by their poor physical properties in response to mechanical loads, including weak gel strength, brittleness, and permanent deformation. Recently, interpenetrating polymer network (IPN) hydrogels have gained substantial attention for their use in investigating changes in encapsulated cell behaviors under mechanical stimulation. However, despite recent success in developing highly elastic IPN-structured hydrogels, it remains a great technical challenge to endow them with biocompatibility and biodegradability due to use of toxic chemicals, nonbiodegradable prepolymers, and harsh reaction conditions. In this study, we report on the synthesis and formation of highly elastic and tough IPN-structured hydrogels based on alginate and gelatin, which are biocompatible and biodegradable. Mechanical stimulation enhanced the proliferation and osteogenic differentiation of encapsulated human mesenchymal stem cells in the IPN-structured hydrogels. These new biocompatible, biodegradable, and tough elastomeric hydrogels provide an exciting platform for studying stem cell behaviors such as proliferation and differentiation under mechanical stimulation and may broaden the applications of hydrogels in the fields of tissue engineering and regenerative medicine.