Extracellular matrix bioink boosts stemness and facilitates transplantation of intestinal organoids as a biosafe Matrigel alternative.

Organoids hold inestimable therapeutic potential in regenerative medicine and are increasingly serving as an in vitro research platform. Still, their expanding applications are critically restricted by the canonical culture matrix and system. Synthesis of a suitable bioink of bioactivity, biosecurity, tunable stiffness, and printability to replace conventional matrices and fabricate customized culture systems remains challenging. Here, we envisaged a novel bioink formulation based on decellularized extracellular matrix (dECM) from porcine small intestinal submucosa for organoids bioprinting, which provides intestinal stem cells (ISCs) with niche-specific ECM content and biomimetic microstructure. Intestinal organoids cultured in the fabricated bioink exhibited robust generation as well as a distinct differentiation pattern and transcriptomic signature. This bioink established a new co-culture system able to study interaction between epithelial homeostasis and submucosal cells and promote organoids maturation after transplantation into the mesentery of immune-deficient NODSCID-gamma (NSG) mice. In summary, the development of such photo-responsive bioink has the potential to replace tumor-derived Matrigel and facilitate the application of organoids in translational medicine and disease modeling.

Fabrication of gelatin-based printable inks with improved stiffness as well as antibacterial and UV-shielding properties.

Gelatin-based inks have a broad range of applications in bioprinting for tissue engineering and regenerative medicine due to their biocompatibility, ease of modification, degradability, and rapid gelation induced by low temperature. However, gelatin-derived inks prepared through low-temperature treatment have poor mechanical properties that limit their applications. To solve this problem, we designed polyacrylamide/gelatin/silver nanoparticle (PAAm-GelatinAgNPs) ink to improve gelatin-based hydrogels. The ink is based on double networks, in which the physically cross-linked gelatin as the first network and covalently cross-linked PAAm as the second network. It was found that the presence of PAAm increased the tensile and compression strength of the gelatin-based ink. Moreover, silver nanoparticles endowed the antibacterial properties to the gelatin-based ink and were able to shield the UV irradiation and damages to rat skin. In addition, this ink showed the shear thinning property; Consequently it succeeded in printing complex 3D scaffolds such as the cube, five-pointed star, flower, and university logo of "SEU". In summary, this ink presents a new strategy for the modification of gelatin and offers new potential applications for customized therapy of antimicrobial and anti-UV damage to tissues.