Photodegradable polyacrylamide tanglemers enable spatiotemporal control over chain lengthening in high-strength and low-hysteresis hydrogels.

Covalent hydrogel networks suffer from a stiffness-toughness conflict, where increased crosslinking density enhances the modulus of the material but also leads to embrittlement and diminished extensibility. Recently, strategies have been developed to form highly entangled hydrogels, colloquially referred to as tanglemers, by optimizing polymerization conditions to maximize the density and length of polymer chains and minimize the crosslinker concentration. It is challenging to assess entanglements in crosslinked networks beyond approximating their theoretical contribution to mechanical properties; thus, in this work, we synthesize and characterize polyacrylamide tanglemers using a photolabile crosslinker, which allows for direct assessment of covalent trapping of entanglements under tension.

A Covalent Chemical Probe for nsP2 Cysteine Protease with Antialphaviral Activity and Proteome-wide Selectivity.

RA-0003022 () was identified as a high-quality covalent chemical probe for nsP2 cysteine protease (nsP2pro). Isoxazole covalently captured the active site C478 and inactivated the enzyme with a / ratio of 6000 Ms. A negative control analog RA-0025453 () retained the covalent warhead but demonstrated >100-fold decrease in enzyme inhibition.

Dopaminergic Axon Tracts Within a Hyaluronic Acid Hydrogel Encasement to Restore the Nigrostriatal Pathway.

Parkinson's disease is characterized by motor deficits emerging from insufficient dopamine in the striatum after degeneration of dopaminergic neurons and their long-projecting axons comprising the nigrostriatal pathway. To address this, a tissue-engineered nigrostriatal pathway (TE-NSP) featuring a tubular hydrogel with a collagen/laminin core that encases aggregated dopaminergic neurons and their axonal tracts is developed. This engineered microtissue can be implanted to replace neurons and axons with fidelity to the lost pathway and thus may provide dopamine according to feedback from host circuitry.

Engineered Shape-Morphing Transitions in Hydrogels Through Suspension Bath Printing of Temperature-Responsive Granular Hydrogel Inks.

4D printing of hydrogels is an emerging technology used to fabricate shape-morphing soft materials that are responsive to external stimuli for use in soft robotics and biomedical applications. Soft materials are technically challenging to process with current 4D printing methods, which limits the design and actuation potential of printed structures. Here, a simple multi-material 4D printing technique is developed that combines dynamic temperature-responsive granular hydrogel inks based on hyaluronic acid, whose actuation is modulated via poly(N-isopropylacrylamide) crosslinker design, with granular suspension bath printing that provides structural support during and after the printing process.

Prognostic and therapeutic implications of tumor-restrictive type III collagen in the breast cancer microenvironment.

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and bioinformatic experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer.