A Systematic Study of GelMA-Carbopol Bioinks for High-Fidelity Extrusion 3D Bioprinting at Physiological Temperatures

Extrusion 3D bioprinting allows depositing cells within hydrogels in well-defined spatial patterns, facilitating the creation of tissue biomimetics. Gelatin methacrylate (GelMA) hydrogels are biocompatible, biodegradable, and promote cell adhesion, making them a common choice to formulate bioinks. However, the low viscosity of GelMA-based inks makes it challenging to print at physiological temperatures. Typically, this is overcome with high concentrations (≥ 10%) of GelMA and rheological modifiers (≥ 1%), and using low temperatures, which negatively impact the printing process and cell function. This work develops high performance GelMA bioinks using Carbopol (CBP) as a rheology modifier. Inks containing low GelMA and CBP concentrations exhibit excellent printability at physiological temperatures. Complex constructs, including hollow structures with overhangs, were 3D printed with high shape fidelity. The inks show excellent cytocompatibility toward various cells, including primary human lung fibroblasts (HLF). HLF embedded in bioprinted structures exhibited outstanding viability and proliferated over 14 days of continuous culture. As an application, GelMA-CBP inks were used to fabricate a stretchable lung tissue model incorporating HLFs, which was used to study fibroblast-to-myofibroblast transition. This work resolves limitations of traditional GelMA 3D bioprinting inks and lays the foundation for their use in advanced tissue biomimetics and regenerative medicine applications.