Beta cell dysfunction occurs independently of insulitis in type 1 diabetes pathogenesis.

During type 1 diabetes (T1D) progression, beta cells become dysfunctional and exhibit reduced first-phase insulin release. While this period of beta cell dysfunction is well established, its cause and underlying mechanism remain unknown. To address this knowledge gap, live human pancreas tissue slices were prepared from autoantibody- negative organ donors without diabetes (ND), donors positive for one or more islet autoantibodies (AAb+), and donors with T1D within 0-4 years of diagnosis (T1D+).

Granular Hydrogels for Harnessing the Immune Response.

This review aims to understand the current progress in immune-instructive granular hydrogels and identify the key features used as immunomodulatory strategies. Published work is systematically reviewed and relevant information about granular hydrogels used throughout these studies is collected. The base polymer, microgel generation technique, polymer crosslinking chemistry, particle size and shape, annealing strategy, granular hydrogel stiffness, pore size and void space, degradability, biomolecule presentation, and drug release are cataloged for each work.

Functional Interrogation of Ca Signals in Human Cancer Cells In Vitro and Ex Vivo by Fluorescent Microscopy and Molecular Tools.

Genetically encoded calcium indicators (GECIs) and high-resolution confocal microscopy enable dynamic visualization of calcium signals in cells and tissues. Two-dimensional and 3D biocompatible materials mimic the mechanical microenvironments of tumor and healthy tissues in a programmable manner. Cancer xenograft models and ex vivo functional imaging of tumor slices reveal physiologically relevant functions of calcium dynamics in tumors at different progression stages.

Single versus dual microgel species for forming guest-host microporous annealed particle PEG-MAL hydrogel.

Inter-particle secondary crosslinks allow microporous annealed particle (MAP) hydrogels to be formed. Methods to introduce secondary crosslinking networks in MAP hydrogels include particle jamming, annealing with covalent bonds, and reversible noncovalent interactions. Here, we investigate the effect of two different approaches to secondary crosslinking of polyethylene glycol (PEG) microgels via reversible guest-host interactions.

Injectable Microporous Annealed Particle Hydrogel Based on Guest-Host-Interlinked Polyethylene Glycol Maleimide Microgels.

Microporous annealed particle (MAP) hydrogels have emerged as a versatile biomaterial platform for regenerative medicine. MAP hydrogels have been used for the delivery of cells and organoids but often require annealing post injection by an external source. We engineered an injectable, self-annealing MAP hydrogel with reversible interparticle linkages based on guest-host functionalized polyethylene glycol maleimide (PEG-MAL) microgels.

Guest-host interlinked PEG-MAL granular hydrogels as an engineered cellular microenvironment.

We report the development of a polyethylene glycol (PEG) hydrogel scaffold that provides the advantages of conventional bulk PEG hydrogels for engineering cellular microenvironments and allows for rapid cell migration. PEG microgels were used to assemble a densely packed granular system with an intrinsic interstitium-like negative space. In this material, guest-host molecular interactions provide reversible non-covalent linkages between discrete PEG microgel particles to form a cohesive bulk material.