Digital light processing of photo-crosslinkable gelatin to create biomimetic 3D constructs serving small intestinal tissue regeneration

IF 5.5 2区医学 Q2 MATERIALS SCIENCE, BIOMATERIALS

Materials Science & Engineering C-Materials for Biological Applications Pub Date : 2025-02-14 DOI:10.1016/j.bioadv.2025.214232

Laure Maes , Anna Szabó , Jens Van Haevermaete , Indi Geurs , Koen Dewettinck , Roosmarijn E. Vandenbroucke , Sandra Van Vlierberghe , Debby Laukens

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引用次数: 0

Abstract

Regeneration of small intestinal mucosal tissue could offer a promising strategy for Crohn's disease patients suffering from chronic inflammatory damage. Here, we aimed to develop hydrogels that mirror the villi and crypts of the small intestine and exhibit a physiological stiffness of G' ~ 1.52 kPa. For this purpose, we developed gelatin-methacryloyl-aminoethyl-methacrylate (gel-MA-AEMA)-, and gelatin-methacryloyl-norbornene (gel-MA-NB)-based biomaterial inks to fabricate 3D hydrogels (“villi only” versus “crypts and villi”) with digital light processing (DLP) and co-cultured Caco-2/HT29-MTX cells. Gel-MA-AEMA was selected for its higher amount of methacrylates which was hypothesized to provide superior photo-crosslinking kinetics and hence superior DLP fabrication potential while gel-MA-NB was evaluated for its selective functionalization potential with thiolated bioactive compounds following DLP processing, resulting from its incorporated NB moieties which remain unreacted during the DLP process. Both gel-MA-AEMA-, and gel-MA-NB-based hydrogels exhibited a physiologically relevant stiffness, but only the gel-MA-AEMA-based biomaterial ink could be successfully utilized for printing hydrogels encompassing villi and crypts. Paracellular permeability of small sized marker molecules in combination with transepithelial electrical resistance measurements showed the formation of a functional barrier over time on all hydrogel constructs. Transmission electron microscopy and enterocyte differentiation marker genes' expression levels revealed the superior differentiation of Caco-2 on the 3D constructs compared to 2D hydrogel sheets. In summary, while both hydrogels enhanced functional barrier formation and enterocyte differentiation, gel-MA-AEMA proved more conducive to DLP compared to gel-MA-NB. Furthermore, our study underscored the benefits of cultivating intestinal cells on soft 3D constructs, enhancing cell barrier properties and differentiation, thus providing added value over traditional 2D supports.

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来源期刊

Materials Science & Engineering C-Materials for Biological Applications 工程技术-材料科学：生物材料

CiteScore

17.80

自引率

0.00%

发文量

501

审稿时长

27 days

期刊介绍： Biomaterials Advances, previously known as Materials Science and Engineering: C-Materials for Biological Applications (P-ISSN: 0928-4931, E-ISSN: 1873-0191). Includes topics at the interface of the biomedical sciences and materials engineering. These topics include: • Bioinspired and biomimetic materials for medical applications • Materials of biological origin for medical applications • Materials for "active" medical applications • Self-assembling and self-healing materials for medical applications • "Smart" (i.e., stimulus-response) materials for medical applications • Ceramic, metallic, polymeric, and composite materials for medical applications • Materials for in vivo sensing • Materials for in vivo imaging • Materials for delivery of pharmacologic agents and vaccines • Novel approaches for characterizing and modeling materials for medical applications Manuscripts on biological topics without a materials science component, or manuscripts on materials science without biological applications, will not be considered for publication in Materials Science and Engineering C. New submissions are first assessed for language, scope and originality (plagiarism check) and can be desk rejected before review if they need English language improvements, are out of scope or present excessive duplication with published sources. Biomaterials Advances sits within Elsevier''s biomaterials science portfolio alongside Biomaterials, Materials Today Bio and Biomaterials and Biosystems. As part of the broader Materials Today family, Biomaterials Advances offers authors rigorous peer review, rapid decisions, and high visibility. We look forward to receiving your submissions!