Bioactive photocrosslinkable resin solely based on refined decellularized small intestine submucosa for vat photopolymerization of in vitro tissue mimics
L. Elomaa, L. Gerbeth, A. Almalla, N. Fribiczer, P. Tang, K. Hillebrandt, I.M. Sauer, S. Seiffert, B. Siegmund, M. Weinhart – 2023
Three-dimensionally (3D) printed tissue mimics are unique in vitro platforms for studying human pathophysiology in a more physiologically relevant manner compared to oversimplified 2D cell cultures and complex animal models. However, their 3D printing requires an availability of materials that at the same time show a high level of biomimicry and also have a suitable viscosity profile and crosslinking kinetics for the desired printing technique. We developed a new biomimetic material for vat photopolymerization by solubilizing and functionalizing porcine small intestine submucosa (dSIS) into photocrosslinkable dSIS methacryloyl (dSIS-MA) and by subsequently formulating it into a bioactive 3D printing resin. The concentration of 1.5 wt% of dSIS-MA yielded desired viscosity and photocrosslinking kinetics, and the 3D printing of the resin resulted in fully transparent and highly swelling dSIS-MA hydrogels with a stiffness resembling native intestinal tissue. The new dSIS-MA resin was successfully 3D printed into acellular intestine-mimicking scaffolds that desirably guided the seeded human intestinal cells to grow along the 3D villi mimics. Human small intestinal organoid-derived undifferentiated primary cells grew to confluency on the dSIS-MA hydrogels and formed continuous tight junctions, thereby demonstrating the suitability of the 3D printing material for growing intestinal epithelium mimics. Furthermore, a small fraction of the human primary intestinal cells produced mucin 5AC, demonstrating early differentiation of these cells on the dSIS-MA hydrogels. The excellent cell compatibility of the dSIS-MA material combined with its high printability and biomimicry indicated that this new resin can be a great help in modelling and reproducing native tissue architectures where enhanced physiological relevancy is desired.