Leveraging Blood Components for 3D Printing Applications Through Programmable Ink Engineering Approaches

This study proposes a tunable ink engineering methodology to allow 3D printing processability of highly bioactive but otherwise low-viscous and unprintable blood-derived materials. The hypothesis relies on improving the viscoelasticity and shear thinning behavior of platelet lysates (PL) and albumins (BSA) solutions by covalent coupling, enabling simultaneous extrusion and photocrosslinking upon filament deposition. The available amine groups on proteins (PL and BSA) are exploited for coupling with carboxyl groups present in methacrylated proteins (hPLMA and BSAMA), by leveraging carbodiimide chemistry. This reaction enabled the creation of a pre-gel from these extremely low-viscous materials (approximate to 1 Pa), with precise tuning of the reaction, resulting in inks with a range of controlled viscosities and elasticities. Shape-fidelity analysis is performed on 3D-printed multilayered constructs, demonstrating the ability to reach clinically relevant sizes (>2 cm in size). After photocrosslinking, the scaffolds showcased a mechanically robust structure with sustained protein release over time. Bioactivity is evaluated using human adipose-derived stem cells, resulting in increased viability and metabolic activity over time. The herein described research methodology widens the possibilities for the use of low-viscosity materials in 3D printing but also enables the direct application of patient and blood-derived materials in precision medicine.