Post-Cross-Linking of Collagen Hydrogels by Carboxymethylated Polyrotaxanes for Simultaneously Improving Mechanical Strength and Cell Proliferation

Abstract

To improve the mechanical properties of collagen hydrogels, which are widely utilized as biomaterials, post-cross-linking of collagen hydrogels was performed using polyrotaxane (PRX) as a cross-linker. Herein, carboxymethyl group-modified PRXs (CMPRs) composed of carboxymethylated α-cyclodextrins (α-CDs) threaded along poly­(ethylene glycol) (PEG) capped with bulky stoppers were used to cross-link via reaction with the amino groups in the collagen. Four series of CMPRs with different α-CD threading ratios and axle PEG molecular weights were used for the post-cross-linking of the collagen hydrogels to verify the optimal CMPR chemical compositions. The post-cross-linking of the collagen hydrogels with CMPRs improved the swelling ratios and mechanical properties, such as viscoelasticity and tensile strength. Among the tested CMPRs, CMPRs with an axle PEG molecular weight of 35,000 (PEG35k) resulted in better mechanical properties than CMPRs with a PEG10k axis. Additionally, the cell adhesion and proliferation were greatly improved on the surface of the collagen hydrogels post-cross-linked with CMPRs with the PEG35k axle. These findings suggest that the molecular weight of an axle polymer in CMPRs is a more important parameter than the α-CD threading ratios. Accordingly, the post-cross-linking of hydrogels with PRXs is promising for improving the mechanical properties and biomaterial functions of collagen hydrogels.

Synthesis, Characterization, and Potential Application of Cyclodextrin-Based Polyrotaxanes for Reinforced Atelocollagen Threads

“…Both the fracture stress and strain were enhanced by increasing the molecular weight of the PRs from 20,000 to 100,000, which indicated that the increased effective range of αCD resulting from the higher molecular weight significantly affected the gel mechanical properties. A similar effect of molecular weight was reported for atelocollagen hydrogels post-crosslinked with carboxymethyl PRs [58]. Note that molecular weight exerted a stronger effect on the fracture stress and strain than coverage ratio in the previous studies.…”

Mechanically Tunable Hydrogels with Self-Healing and Shape Memory Capabilities from Thermo-Responsive Amino Acid-Derived Vinyl Polymers

“…To address this issue, PNAGAm-containing Ser-based reactive hydroxy groups, which allow post-crosslinking of the gel, were synthesized via the simple copolymerization of N-acryloyl glycinamide (NAGAm) and NASMe. Post-crosslinking of hydrogel materials is a useful strategy to tune their mechanical properties, particularly in biopolymer-based self-assembling systems [46,47].…”