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

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Laura Elomaa
  • Lorenz Gerbeth
  • Ahed Almalla
  • Nora Fribiczer
  • Peter Tang
  • Karl Hillebrandt
  • Igor Maximillian Sauer
  • Sebastian Seiffert
  • Britta Siegmund
  • Marie Weinhart

External Research Organisations

  • Freie Universität Berlin (FU Berlin)
  • Charité - Universitätsmedizin Berlin
  • Johannes Gutenberg University Mainz
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Details

Original languageEnglish
Article number103439
JournalAdditive Manufacturing
Volume64
Early online date1 Feb 2023
Publication statusPublished - 25 Feb 2023

Abstract

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.

Cite this

Bioactive photocrosslinkable resin solely based on refined decellularized small intestinal submucosa for digital light processing 3D printing of in vitro tissue mimics. / Elomaa, Laura; Gerbeth, Lorenz; Almalla, Ahed et al.
In: Additive Manufacturing, Vol. 64, 103439, 25.02.2023.

Research output: Contribution to journalArticleResearchpeer review

Elomaa L, Gerbeth L, Almalla A, Fribiczer N, Tang P, Hillebrandt K et al. Bioactive photocrosslinkable resin solely based on refined decellularized small intestinal submucosa for digital light processing 3D printing of in vitro tissue mimics. Additive Manufacturing. 2023 Feb 25;64:103439. Epub 2023 Feb 1. doi: 10.26434/chemrxiv-2022-f2hpc, 10.1016/j.addma.2023.103439
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title = "Bioactive photocrosslinkable resin solely based on refined decellularized small intestinal submucosa for digital light processing 3D printing of in vitro tissue mimics",
abstract = "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.",
author = "Laura Elomaa and Lorenz Gerbeth and Ahed Almalla and Nora Fribiczer and Peter Tang and Karl Hillebrandt and Sauer, {Igor Maximillian} and Sebastian Seiffert and Britta Siegmund and Marie Weinhart",
note = "Funding Information: The authors warmly thank Dahlem Research School and the Focus Area Nanoscale at Freie Universit{\"a}t 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",
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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.

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