The use and incorporation of type I collagen (COL) in biomaterials and regenerative medicine has remained challenging due to COL’s ability to spontaneously polymerize at physiological pH in vitro. In an in vivo environment, collagenous connective tissues are reliant on constant self-repair to continuously function, and it has been hypothesized that glycosaminoglycans transport soluble, neutralized COL to these cellular restricted areas. We proposed that we could utilize monosaccharides, the fundamental unit of glycosaminoglycans, to regulate COL assembly in vitro to alleviate the challenges associated with working with COL. To test this, we explored the effects of the monosaccharides that populate glycosaminoglycans of the extracellular matrix on collagen assembly kinetics via turbidimetric assays. Results showed that the addition of monosaccharides can delay COL polymerization and increase its solubility by three orders of magnitude at neutral conditions — two features that improve the utility of COL in in vitro applications. We expanded on these findings and described the thermodynamic effects of these monosaccharides on the growth phase of COL polymerization by deriving van’t Hoff plots. We used this data to support an indirect mechanism for delayed COL assembly profiles based on solvent ordering. We observed that the presence of monosaccharides during COL fibril assembly neither altered the substructure of the fibrils, nor dissociated a pre-existing fibrillar network. Fluorescent-labeling studies illustrated that in the presence of monosaccharide solutions, soluble COL maintains the functional capacity to integrate into a pre-existing COL network. Finally, we demonstrated a proof-of-concept study which showed how the presence of these sugars aided in the delivery of a high concentration of neutralized monomeric COL into simple patterns without disrupting COL structure formation. Overall, our findings support the application of entropy-regulating systems like monosaccharides in manipulating the dynamics of COL assembly to aid in biomaterials design.

Role for monosaccharides in the nucleation inhibition and transport of collagen for materials design

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.