Investigating the Thermodynamics Underlying Monosaccharide-Mediated Collagen Polymerization for Materials Design

The use and incorporation of type I collagen (COL) in biomaterials and regenerative medicine have remained challenging due to COL’s ability to spontaneously polymerize at physiological pH in vitro. Previous work has shown that the addition of monosaccharides can delay COL polymerization and increase its solubility under neutral conditions by three orders of magnitude─two features that enable structure retention and integration into pre-existing fibrous networks. We expand on these findings and describe the thermodynamic effects of these monosaccharides on the growth phase of COL polymerization. We derive van’t Hoff plots for each experimental condition and use these data to support an indirect mechanism for delayed COL assembly profiles based on solvent ordering. We observe that the presence of monosaccharides in a COL solution neither altered nor permanently inhibited the formation of COL fibrils. Finally, we demonstrate the utility of our findings through a proof-of-concept study which showed how the presence of these monosaccharides aided in the delivery of a high (2 mg/mL) concentration of neutralized, monomeric COL into simple patterns without disrupting COL structure formation. Our findings support the application of entropy-regulating systems such as monosaccharides in manipulating the dynamics of some self-assembling proteins to aid in biomaterials design.