WEB Preparation Shear-Thinning and Self-Healing Hydrogels Based on Hydrophobically Modified Hyaluronic Acid for 3D printing
Objectives: developing novel biodegradable and biocompatible hydrogels with rheological properties that are able to meet critical requirements of 3D bioprinting becomes currently an appealing research topic in the field of biomaterial science. The present study describes a systematic investigation in this direction carried out by synthesis a series of alkyl-modified hyaluronic acid (HA) in order to reach the best polymer composition, which can form a suitable hydrogel for 3D bioprinting.
Methods: For this study, HA chains of two molar masses Mw= 40 and 80 kDa were hydrophobically modified using either hexadecyl chains (HD) or dodecyl chains (DD) with different modification ratios. The rheological properties of the synthesized polymers were investigated using rheometry.
Results: The ratio of modification of the synthesized polymers was characterized using 1HNMR spectroscopy. The ability of these polymers to form a stable gel in PBS at polymer concentration of 4 wt % was investigated. The results revealed that regardless of the molar mass of the utilized HA, the polymers modified using HD chains were not soluble in PBS when the degree of substitution was ≥ 20 mol% whereas the polymers with low substitution degree ≤ 5 mol%, can form only a viscous solution at this polymer concentration. The continuous flow experiments carried out on the prepared hydrogels showed a dramatic decrease of the viscosity of all tested hydrogels upon increasing the shearing rate indicating that all prepared hydrogels have shear-thinning behavior. The cyclic strain time sweep rheology experiments showed a sharp decrease in the storage modules of the tested hydrogels upon applying high strain, which was instantly recovered by applying low strain indicating a good self-healing behavior.
Conclusion: Introducing hydrophobic alkyl short chains onto HA backbones enables the modified polymers to form a hydrogels at relatively low polymer concentration due the physical interaction between the attached side chains. The shear-thinning as well as the self-healing behavior shown for the tested hydrogels via rheological experiments make them candidate for the extrusion-based 3D bioprinting technique. The printability beside the biocompatibility of these gels are currently tested.
Acknowledgment: the authors would like thank the European Research Council (ERC) for the financial support.