Tissue-specific hydrogels derived from decellularized extracellular matrix with adjustable mechanical properties: characterization and applications in the (bio)medical field

Abstract

Extrusion-based 3D bioprinting is one of the most used technologies to fabricate complex biological structures. A compromise between printability and biocompatibility is needed to make bioinks, or hydrogels, suitable for these applications. It means that adequate rheological behavior and shape retention, as well as the ability of providing a cell-friendly and pro-regenerative environment, are necessary. Hydrogels derived from decellularized extracellular matrix (dECM) are of special interest for the formulation of bioinks as they provide tissue-specific properties and signals. Although these hydrogels represent the biochemical microenvironment very well, they still lack adequate rheological and biomechanical properties. During the PIPE Phase 1 project, we used a physical reinforcement approach to optimize a bioink formulation based on dECM and polysaccharides that combines printability and biocompatibility. In addition, we explored the use of a chemical crosslinking agent and showed that the use of this compound can generate hydrogels that are more resistant and easier to handle. Now, in this second phase of the PIPE, we will carry out the translation of the findings that were obtained previously to one of the types of dECM, the aorta, to formulations containing different types of decellularized tissues and organs, namely: adipose tissue, bone, cartilage , muscle, myocardium, lung, skin, brain, kidney, liver, spleen, pancreas, colon and stomach. The conditions used for each type of reinforcement are adjustable, so the stiffness of the final material can be tuned to the desired application. In addition to the biochemical, rheological and biomechanical characterization of hydrogels, their influence on cell adhesion, viability, proliferation and differentiation will be investigated. We also propose the bioprinting of a model of osteochondral tissue with a gradient of biomechanical properties conferred by the use of different bioinks, in order to demonstrate the spatially directed differentiation of adipose tissue-derived stem cells. Finally, to demonstrate the bioprinting of a soft tissue, we propose the 3D bioprinting of a ventricle model in a support bath, using, for this, cardiomyocytes derived from induced pluripotent stem cells (iPSC-CM). From these results, we hope to create a product line - based on the different tissues studied - for researchers working in different areas of the biomedical sciences. (AU)