Effect of temperature on gelation and cross-linking of gelatin methacryloyl for biomedical applications

Hydrogels with or without chemical cross-linking have been studied and used for biomedical applications, such as tissue repair, surgical sealants, and three dimensional biofabrication. These materials often undergo a physical sol-gel or gel-sol transition between room and body temperatures and can also be chemically cross-linked at these temperatures to give dimensional stability. However, few studies have clearly shown the effect of heating/cooling rates on such transitions. Moreover, only a little is known about the effect of cross-linking temperature or the state on the modulus after cross-linking. We have established rheological methods to study these effects, an approach to determine transition temperatures, and a method to prevent sample drying during measurements. All the rheological measurements were performed minimizing the normal stress build-up to compensate for the shrinking and expansion due to temperature and phase changes. We chemically modified gelatin to give gelatin methacryloyl and determined the degree of methacryloylation by proton nuclear magnetic resonance. Using the gelatin methacryloyl as an example, we have found that the gel state or lower temperature can give more rigid gelatin-based polymers by cross-linking under visible light than the sol state or higher temperature. These methods and results can guide researchers to perform appropriate studies on material design and map applications, such as the optimal operating temperature of hydrogels for biomedical applications. We have also found that gelation temperatures strongly depend on the cooling rate, while solation temperatures are independent of the heating rate.