Chemistry matters: A side-by-side comparison of two chemically distinct methacryloylated dECM bioresins for vat photopolymerization

Almalla, Ahed; Elomaa, Laura; Fribiczer, Nora; Landes, Timm; Tang, Peng; Mahfouz, Zeinab; Koksch, Beate; Hillebrandt, Karl Herbert; Sauer, Igor Maximilian; Heinemann, Dag; Seiffert, Sebastian; Weinhart, Marie

doi:10.1016/j.bioadv.2024.213850

Cited by 1 publication

(2 citation statements)

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“…Furthermore, the analysis of CD demonstrated the maintenance of protein structural integrity in the dSIS-MA biomaterial resin following chemical functionalization (Figure S2D). Standardized quality control measurements are imperative for each new dSIS-MA batch, as this ensures the consistency and reliability of the resulting material properties [43].…”

Section: Dsis-ma-based Hydrogel Scaffolds For Advanced Small Intestin...mentioning

confidence: 99%

“…S3: Jumper pins configuration of the X,Y,Z, and A axes for the step motors; Figure S10: settings for different configuration modes of standard micro-stepping and a photograph of the operational quarter step mode set on Arduino board; Figure S11: Step-by-step assembly of the Arduino-controlled pump system. References [32,33,43,56] are cited in the Supplementary Materials.…”

Section: Supplementary Materialsmentioning

confidence: 99%

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Hydrogel-Integrated Millifluidic Systems: Advancing the Fabrication of Mucus-Producing Human Intestinal Models

Almalla,

Alzain,

Elomaa

et al. 2024

Cells

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The luminal surface of the intestinal epithelium is protected by a vital mucus layer, which is essential for lubrication, hydration, and fostering symbiotic bacterial relationships. Replicating and studying this complex mucus structure in vitro presents considerable challenges. To address this, we developed a hydrogel-integrated millifluidic tissue chamber capable of applying precise apical shear stress to intestinal models cultured on flat or 3D structured hydrogel scaffolds with adjustable stiffness. The chamber is designed to accommodate nine hydrogel scaffolds, 3D-printed as flat disks with a storage modulus matching the physiological range of intestinal tissue stiffness (~3.7 kPa) from bioactive decellularized and methacrylated small intestinal submucosa (dSIS-MA). Computational fluid dynamics simulations were conducted to confirm a laminar flow profile for both flat and 3D villi-comprising scaffolds in the physiologically relevant regime. The system was initially validated with HT29-MTX seeded hydrogel scaffolds, demonstrating accelerated differentiation, increased mucus production, and enhanced 3D organization under shear stress. These characteristic intestinal tissue features are essential for advanced in vitro models as they critically contribute to a functional barrier. Subsequently, the chamber was challenged with human intestinal stem cells (ISCs) from the terminal ileum. Our findings indicate that biomimicking hydrogel scaffolds, in combination with physiological shear stress, promote multi-lineage differentiation, as evidenced by a gene and protein expression analysis of basic markers and the 3D structural organization of ISCs in the absence of chemical differentiation triggers. The quantitative analysis of the alkaline phosphatase (ALP) activity and secreted mucus demonstrates the functional differentiation of the cells into enterocyte and goblet cell lineages. The millifluidic system, which has been developed and optimized for performance and cost efficiency, enables the creation and modulation of advanced intestinal models under biomimicking conditions, including tunable matrix stiffness and varying fluid shear stresses. Moreover, the readily accessible and scalable mucus-producing cellular tissue models permit comprehensive mucus analysis and the investigation of pathogen interactions and penetration, thereby offering the potential to advance our understanding of intestinal mucus in health and disease.

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Section: Dsis-ma-based Hydrogel Scaffolds For Advanced Small Intestin...mentioning

confidence: 99%

Section: Supplementary Materialsmentioning

confidence: 99%

Hydrogel-Integrated Millifluidic Systems: Advancing the Fabrication of Mucus-Producing Human Intestinal Models

Almalla,

Alzain,

Elomaa

et al. 2024

Cells

Self Cite

View full text Add to dashboard Cite

show abstract

Chemistry matters: A side-by-side comparison of two chemically distinct methacryloylated dECM bioresins for vat photopolymerization

Cited by 1 publication

References 61 publications

Hydrogel-Integrated Millifluidic Systems: Advancing the Fabrication of Mucus-Producing Human Intestinal Models

Hydrogel-Integrated Millifluidic Systems: Advancing the Fabrication of Mucus-Producing Human Intestinal Models

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