Bioinks, an emerging high-potential class of materials in modern biomedicine, rely on hydrogels as key components to ensure printability and structural stability in biofabrication. In this regard, we previously demonstrated the suitability of thermogelling diblock copolymers comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine) for extrusion printing.[1] Further, post-printing and crosslinking performed cytocompatibility tests confirmed the frameworks applicability in bioink formulation. Building on these findings, we sought to enhance our bioinks versatility by introducing a molecular handle for potentially reversible crosslinking.

The functionality enables flexibility in (de-)polymerization methods via radical, UV, thiolate or reductive mechanisms, enabling (possibly reversible) covalent crosslinking. Importantly, the introduced materials have interesting properties for applications in wound care[2] and drug delivery systems[3].

By integrating the novel functionalities into our copolymer system, we envisioned to combine their respective distinct advantages into a novel bioink framework: The copolymer backbone provides critical thermogelling and shear-thinning properties essential for 3D printing, while the novel moiety provides a degradable, versatile crosslinkable component with properties that support wound healing and tissue regeneration.

We present a straightforward two-step post-polymerization modification to synthesize crosslinkable and extrusion printable copolymers. These copolymers form stable and durable hydrogels with thermogelling properties, underlining their suitability for 3D-printing applications.

The printed structures exhibit excellent shape fidelity and resolution, with crosslinking achieved by radical, UV and thiolate mechanisms. The resulting hydrogels are soft, durable, and elastic. Cytocompatibility tests conducted post-printing and crosslinking confirmed the bioink's viability, highlighting its potential for biofabrication.

References

[1] L., Hahn; M., Beudert; M., Gutmann; L. Keßler; P., Stahlhut; L., Fischer; E., Karakaya; T., Lorson; I., Thievessen; R., Detsch; T., Lühmann; R., Luxenhofer;  Macromol. Biosci. 2021, 21, 2100122.

[2] M., Zhang; C., Zhang; Z., Li; X., Fu; S., Huang; Regenerative Biomaterials, 2023, 10, rbac105.

[3] J., Li; D., Mooney; Nat Rev Mater 1, 16071 (2016).