Direct-write 3D printing and characterization of a GelMA-based biomaterial for intracorporeal tissue

We develop and characterize a biomaterial formulation and robotic methods tailored for intracorporeal tissue engineering (TE) via direct-write (DW) 3D printing. Intracorporeal TE is defined as the biofabrication of 3D TE scaffolds inside of a living patient, in a minimally invasive manner. A biomaterial for intracorporeal TE requires to be 3D printable and crosslinkable via mechanisms that are safe to native tissues and feasible at physiological temperature (37 degrees C). The cell-laden biomaterial (bioink) preparation and bioprinting methods must support cell viability. Additionally, the biomaterial and bioprinting method must enable the spatially accurate intracorporeal 3D delivery of the biomaterial, and the biomaterial must adhere to or integrate into the native tissue. Current biomaterial formulations do not meet all the presumed intracorporeal DW TE requirements. We demonstrate that a specific formulation of gelatin methacryloyl (GelMA)/Laponite(R)/methylcellulose (GLM) biomaterial system can be 3D printed at physiological temperature and crosslinked using visible light to construct 3D TE scaffolds with clinically relevant dimensions and consistent structures. Cell viability of 71%-77% and consistent mechanical properties over 21 d are reported. Rheological modifiers, Laponite(R)and methylcellulose, extend the degradation time of the scaffolds. The DW modality enables the piercing of the soft tissue and over-extrusion of the biomaterial into the tissue, creating a novel interlocking mechanism with soft, hydrated native tissue mimics and animal muscle with a 3.5-4 fold increase in the biomaterial/tissue adhesion strength compared to printing on top of the tissue. The developed GLM biomaterial and robotic interlocking mechanism pave the way towards intracorporeal TE.