Probing the aggregation behavior of collagen molecules regulated by dibenzaldehyde-terminated-PEG with varying molecular weights in solution

Rigid and fragile nature of collagen-based materials cross-linked with biocompatible aldehyde-functionalized polysaccharides remains a challenge. Drawing inspiration from the pangolins' protective barrier, we introduce a novel cross-linker with a flexible chain to impart a “rigid-flexible coupled structure” to the collagen-based matrix. Successful integration of dibenzaldehyde-terminated-PEG (DF-PEG) into collagen molecules was confirmed by XRD and FTIR analyses. CD measurements demonstrated that the intact triple-helical structure was preserved in all samples. Distinct effects of DF-PEG with varying molecular weights on the aggregation behavior of collagen molecules were evaluated using multiple quantitative analysis techniques. Specifically, when the molecular weight of DF-PEG was below 20,000, multipoint hydrogen bonds and Schiff-base linkages were produced as the molecular weight of DF-PEG increased, which synergistically enhanced the aggregation behavior of collagen molecules. While the aggregation behavior of collagen molecules was slightly diminished upon the molecular weight of DF-PEG reached 20,000. This reduction can be attributed to the limited accessibility of the molecular reactive sites in the extended DF-PEG chains. Finally, a computational test of the binding interactions between collagen molecules and DF-PEG was conducted to validate the experimental results. Our biomimetic design strategy offers a new approach for the preparation of collagen-based materials with exceptional physicochemical properties.