TY - JOUR

T1 - Bioactive photocrosslinkable resin solely based on refined decellularized small intestinal submucosa for digital light processing 3D printing of in vitro tissue mimics

AU - Elomaa, Laura

AU - Gerbeth, Lorenz

AU - Almalla, Ahed

AU - Fribiczer, Nora

AU - Tang, Peter

AU - Hillebrandt, Karl

AU - Sauer, Igor Maximillian

AU - Seiffert, Sebastian

AU - Siegmund, Britta

AU - Weinhart, Marie

N1 - Funding Information: The authors warmly thank Dahlem Research School and the Focus Area Nanoscale at Freie Universität Berlin (LE), the Federal Ministry of Education and Research (FKZ: 13N13523) (MW), and the German Research Foundation (DFG) for financial support of the current work within the Collaborative Research Centre CRC 1449 (431232613; MW, LE, LH, AA, BS) and the Research Unit FOR 2811 (NF, SS) (Project ID 431232613 and 423791428). Acknowledgment: M.Sc. Peng Tang is kindly acknowledged for taking the SEM images at the Core

PY - 2023/2/25

Y1 - 2023/2/25

N2 - 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.

AB - 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.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85149793021&origin=inward&txGid=f647da1c14d745c4a983fc35b00dfb00

U2 - 10.26434/chemrxiv-2022-f2hpc

DO - 10.26434/chemrxiv-2022-f2hpc

M3 - Article

VL - 64

JO - Additive Manufacturing

JF - Additive Manufacturing

M1 - 103439

ER -