Enhancing biofabrication: Shrink-resistant collagen-hyaluronan composite hydrogel for tissue engineering and 3D bioprinting applications

Abstract

Biofabrication represents a promising technique for creating tissues for regeneration or as models for drug testing. Collagen-based hydrogels are widely used as suitable matrix owing to their biocompatibility and tunable mechanical properties. However, one major challenge is that the encapsulated cells interact with the collagen matrix causing construct shrinkage. Here, we present a hydrogel with high shape fidelity, mimicking the major components of the extracellular matrix. We engineered a composite hydrogel comprising gallic acid (GA)-functionalized hyaluronic acid (HA), collagen I, and HA-coated multiwall carbon nanotubes (MWCNT). This hydrogel supports cell encapsulation, exhibits shear-thinning properties enhancing injectability and printability, and importantly significantly mitigates shrinkage when loaded with human fibroblasts compared to collagen I hydrogels (∼20 % vs. > 90 %). 3D-bioprinted rings utilizing human fibroblast-loaded inks maintain their shape over 7 days in culture. Furthermore, inclusion of HAGA into collagen I hydrogels increases mechanical stiffness, radical scavenging capability, and tissue adhesiveness. Notably, the here developed hydrogel is also suitable for human induced pluripotent stem cell-derived cardiomyocytes and allows printing of functional heart ventricles responsive to pharmacological treatment. Cardiomyocytes behave similar in the newly developed hydrogels compared to collagen I, based on survival, sarcomere appearance, and calcium handling. Collectively, we developed a novel material to overcome the challenge of post-fabrication matrix shrinkage conferring high shape fidelity.