Mathematical modeling of a temperature-sensitive and tissue-mimicking gel matrix

Miniaturized biopolymer gel systems have been attracting interests for the application to regenerative medicine, due to their physiological compatibility/sensitivity and rapid kinetics with response to external stimuli. For explaining such responsivity in terms of gel thermodynamics and mechanics, classical mean-field Flory-Huggins-Rehner theory has long been developed with various analytical and numerical modifications. In this work, we present a novel mathematical model on the volume phase transitions of biological hybrid gels as a function of temperature. In order to mimic living soft tissues, the biological microgels are designed to comprise 3D network of extracellular matrix (ECM) protein chains such as collagen and gelatin, which are covalently cross-linked and remain swollen in aqueous media. Within the network, thermoresponsive synthetic polymer chains are doped by physical entrapment and chemical conjugations. Based on the Flory’s framework, our analytical model phenomenologically predicts well-defined volume phase behaviors of the 3D tissue mimics with response to the change in ambient thermodynamic parameters.