GelMA-Carbopol bioinks with low total solids content for high-fidelity extrusion 3D bioprinting of dynamic tissue biomimetics

Extrusion 3D bioprinting is a technology that allows the deposition of cells within hydrogels in well-defined spatial patterns, facilitating the fabrication of tissue biomimetics. Gelatin methacrylate (GelMA)-based hydrogels are biocompatible, biodegradable, and promote cell adhesion and proliferation, which makes them a common choice to formulate bioinks for extrusion 3D bioprinting. However, due to the low viscosity of GelMA-based inks, it is very difficult to achieve high printability and shape fidelity of complex constructs at physiological temperatures. To overcome this issue, high concentrations of GelMA or rheological modifiers and low temperatures are typically used, with both approaches negatively impacting the printing process and cell viability. The present work develops new GelMA-based bioinks using low concentrations of Carbopol (CBP) (0.1-0.5 wt%) as a rheology modifier. GelMA-CBP inks exhibit excellent rheological properties and outstanding printability at physiological temperatures (37 ºC) and at low GelMA concentrations (1–7 wt%). Complex constructs, including hollow structures with overhangs, were printed at 37 ºC with high shape fidelity using 0.5 wt% CBP. 3T3 fibroblasts embedded within structures 3D printed using GelMA-CBP bioinks exhibited > 90% cell viability for up to 14 days. GelMA-CBP bioinks also enabled the fabrication of a stretchable lung tissue model incorporating primary human lung fibroblasts to study fibroblast-to-myofibroblast transition. This work solves the three key issues of GelMA-based bioinks for extrusion 3D bioprinting, by allowing the printing of complex constructs using i) low concentrations of GelMA, ii) low concentrations of a rheological modifier, and iii) physiological temperatures. Our work lays the foundation for using 3D printable GelMA materials in tissue engineering, regenerative medicine, and implantable medical device applications.