Three-Dimensional Printing of a Tyramine Hyaluronan Derivative with Double Gelation Mechanism for Independent Tuning of Shear Thinning and Postprinting Curing

Biofabrication via three-dimensional printing (3DP) is expanding our capabilities of producing tissue engineering constructs for regenerative medicine, personalized medicine, and engineered tissue models of disease and diagnostics. Hydrogel-based materials for extrusion-based printing have been introduced; nevertheless, it is still challenging to combine into a single biomaterial all the requirements of an ink. These inks need to flow for extrusion under low shear, yet have immediate shape retention after deposition, provide a biochemical environment similar to that of physiological extracellular matrix, and a curing mechanism avoiding cell damage. This work introduces a simple and versatile tyramine-modified hyaluronan material (HA-Tyr) for extrusion-based printing, featured by (i) single component yet two distinct cross-linking mechanisms, allowing (ii) shear-Thinning tuning independently of the postprinting curing; (iii) no rheological additives or sacrificial components; (iv) curing with visible light for shape stability; (v) possibility to postfunctionalize; and (vi) preservation of hyaluronan structure owing to low modification degree. The ink is based on a hydroxyphenol hyaluronan derivative, where the shear thinning properties are determined by the enzymatic cross-linking, while the final shape fixation is achieved with visible light in the presence of Eosin Y as photosensitizer. The two cross-linking mechanisms are totally independent. A universal rheologically measurable parameter giving a quantitative measure of the "printability" was introduced and employed for identifying best printability range within the parameter space in a quantitative manner. 3DP constructs were postfunctionalized, and cell-laden constructs were produced. Due to its simplicity and versatility, HA-Tyr can be used for producing a wide variety of 3D printing constructs for tissue engineering applications.