immunocompetent-intestine-on-chip-model-for-analyzing-gut-mucosal

Immunocompetent Intestine-on-Chip Model for Analyzing Gut Mucosal Immune Responses

An advanced intestine-on-chip model recreating epithelial 3D organotypic villus-like and crypt-like structures has been developed. The immunocompetent ...

Jena University Hospital

The human intestinal microbiome substantially affects human health and resistance to infections in its dynamic composition and varying release of microbial-derived metabolites. Short-chain fatty acids (SCFA) produced by commensal bacteria through fermentation of indigestible fibres are considered key regulators in orchestrating the host immune response to microbial colonization by regulating phagocytosis, chemokine and central signalling pathways of cell growth and apoptosis, thereby shaping the composition and functionality of the intestinal epithelial barrier. Although research of the last decades provided valuable insight into the pleiotropic functions of SCFAs and their capability to maintain human health, mechanistic details on how SCFAs act across different cell types and other organs are not fully understood. In this review, we provide an overview of the various functions of SCFAs in regulating cellular metabolism, emphasizing the orchestration of the immune response along the gut-brain, the gut-lung and the gut-liver axes. We discuss their potential pharmacological use in inflammatory diseases and infections and highlight new options of relevant human three-dimensional organ models to investigate and validate their biological functions in more detail.

Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections.

With the incorporation of polyampholytic segments into soft matter, hydrogels can serve as a reservoir for a variety of charged molecules which can be caught and released upon changes in pH value. Asymmetric block extension of one arm for star-shaped poly(ethylene glycol) [PEG -SH] using short segments of polyampholytic poly(dehydroalanine) (PDha) is herein demonstrated while maintaining the functional thiol end groups for network formation. For subsequent hydrogel synthesis with up to 10 wt.% PDha a straightforward and biocompatible photoinitiated thiol-ene click reaction is exploited. The investigation of the swelling properties of the hydrogel revealed responsive behavior toward ionic strength and variations in pH value. Moreover, the reversible adsorption of the model dyes methylene blue (MB) and acid orange 7 (AO7) is investigated by UV-vis measurements and the procedure can be successfully transferred to the adsorption of the adhesion peptide RGDS resulting in an uptake of 1.5 wt% RGDS with regard to the dry weight of the hydrogel.

Asymmetric Block Extension of Star-Shaped [PEG-SH] - toward Poly(dehydroalanine)-Functionalized PEG Hydrogels for Catch and Release of Charged Guest Molecules.

Poly(ethylene glycol)-based (PEG) hydrogels provide an ideal platform to obtain well-defined and tailor-made cell culture matrices to enhance  cell culture conditions, although cell adhesion is often challenging when the cells are cultivated on the substrate surface. We herein demonstrate two approaches for the synthesis of polycationic PEG-based hydrogels which were modified to enhance cell-matrix interactions, to improve two-dimensional (2D) cell culture, and catalyze hydrolytic degradation. While the utilization of ,-(bisacryloxyethyl) amine (BAA) as cross-linker for  gelation provides degradable scaffolds for dynamic cell culture, the incorporation of short segments of poly(-(3-(dimethylamino)propyl)acrylamide) (PDMAPAam) provides high local cationic charge density leading to PEG-based hydrogels with high selectivity for fibroblastic cell lines. The adsorption of transforming growth factor (TGF-β) into the hydrogels induced stimulation of fibrosis and thus the formation of collagen as a natural ECM compound. With this, these dynamic hydrogels enhance  cell culture by providing a well-defined, artificial, and degradable matrix that stimulates cells to produce their own natural scaffold within a defined time frame.

Article	Year
Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections. Open biology\| PubMed ID: 36977462	2023
Asymmetric Block Extension of Star-Shaped [PEG-SH] - toward Poly(dehydroalanine)-Functionalized PEG Hydrogels for Catch and Release of Charged Guest Molecules. Macromolecular bioscience\| PubMed ID: 37572335	2024
Tailoring the Degradation Time of Polycationic PEG-Based Hydrogels toward Dynamic Cell Culture Matrices. ACS applied bio materials\| PubMed ID: 38470448	2024

Valentin D. Wegner

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