3D Printing of Extracellular Matrix-Based Multicomponent, All-Natural, Highly Elastic, and Functional Materials toward Vascular Tissue Engineering

3D printing offers an exciting opportunity to fabricate biological constructs with specific geometries, clinically relevant sizes, and functions for biomedical applications. However, successful application of 3D printing is limited by the narrow range of printable and bio-instructive materials. Multicomponent hydrogel bioinks present unique opportunities to create bio-instructive materials able to display high structural fidelity and fulfill the mechanical and functional requirements for in situ tissue engineering. Herein, 3D printable and perfusable multicomponent hydrogel constructs with high elasticity, self-recovery properties, excellent hydrodynamic performance, and improved bioactivity are reported. The materials' design strategy integrates fast gelation kinetics of sodium alginate (Alg), in situ crosslinking of tyramine-modified hyaluronic acid (HAT), and temperature-dependent self-assembly and biological functions of decellularized aorta (dAECM). Using extrusion-based printing approach, the capability to print the multicomponent hydrogel bioinks with high precision into a well-defined vascular constructs able to withstand flow and repetitive cyclic compressive loading, is demonstrated. Both in vitro and pre-clinical models are used to show the pro-angiogenic and anti-inflammatory properties of the multicomponent vascular constructs. This study presents a strategy to create new bioink whose functional properties are greater than the sum of their components and with potential applications in vascular tissue engineering and regenerative medicine.

Automated summary

3D printing provides an exciting opportunity for fabricating biomedical constructs with specific geometries, sizes, and functions, but is limited by the range of printable and bio-instructive materials. This study reports on the development of printable and perfusable multicomponent hydrogel constructs with high elasticity, self-recovery properties, excellent hydrodynamic performance, and improved bioactivity. The constructs were created using a design strategy that integrates fast gelation kinetics, in situ crosslinking, and temperature-dependent self-assembly. In vitro and pre-clinical models demonstrated the pro-angiogenic and anti-inflammatory properties of the constructs, showcasing their potential applications in vascular tissue engineering and regenerative medicine.