rev-Gelatin: A Gelatin with Reverse Thermo-Responsive Behavior Inspired by Candy and Ice Cubes Phase Dynamics

Conventional gelatin's gel-to-sol transition upon heating restricts its utility in biomedical applications that benefit from a gel state at physiological temperatures such as Pluronic F127 and poly(NIPAAm). Herein, we present "rev-Gelatin", a gelatin engineered with reverse thermo-responsive properties that undergoes a sol-to-gel transition as temperature rises from ambient to body temperature. Inspired by the phase dynamics of common materials like candy and ice cubes, whose surfaces soften or partially melt under warming, facilitating inter-object adhesion- rev-Gelatin leverages this concept to achieve fluidity at room temperature for easy injectability. At ambient temperature, rev-Gelatin exists as a microgel solution with sufficient fluidity in the sol state. However, upon exposure to elevated temperatures approaching physiological temperature, rev-Gelatin microgels coalesce through surface melting, forming a stable gel. This sol-to-gel transition is especially advantageous for hemostatic applications. Upon contact with blood, the temperature elevation induces rapid gelation of rev-Gelatin, effectively creating a barrier that reduces bleeding time and blood loss. Additionally, rev-Gelatin shows promise as a submucosal injection agent for gastrointestinal surgeries, making it a new class of thermo-sensitive biomaterials.