Temperature-responsive hydrogel-grafted vessel-on-a-chip: Exploring cold-induced endothelial injury.

Cold-induced vasoconstriction is a significant contributor that leads to chilblains and hypothermia in humans. However, current animal models have limitations in replicating cold-induced acral injury due to their low sensitivity to cold. Moreover, existing in vitro vascular chips composed of endothelial cells and perfusion systems lack temperature responsiveness, failing to simulate the vasoconstriction observed under cold stress. This study presents a novel approach where a microfluidic bioreactor of vessel-on-a-chip was developed by grafting the inner microchannel surface of polydimethylsiloxane with a thermosensitive hydrogel skin composed of N-isopropyl acrylamide and gelatin methacrylamide. With a lower critical solution temperature set at 30°C, the gel layer exhibited swelling at low temperatures, reducing the flow rate inside the channel by 10% when the temperature dropped from 37°C to 4°C. This well mimicked the blood stasis observed in capillary vessels in vivo. The vessel-on-a-chip was further constructed by culturing endothelial cells on the surface of the thermosensitive hydrogel layer, and a perfused medium was introduced to the cells to provide a physiological shear stress. Notably, cold stimulation of the vessel-on-a-chip led to cell necrosis, mitochondrial membrane potential (ΔΨm) collapse, cytoskeleton disaggregation, and increased levels of reactive oxygen species. In contrast, the static culture of endothelial cells showed limited response to cold exposure. By faithfully replicating cold-induced endothelial injury, this groundbreaking thermosensitive vessel-on-a-chip technology offers promising advancements in the study of cold-induced cardiovascular diseases, including pathogenesis and therapeutic drug screening.

Fabrication of sac-like hydrogel membranes for replicating curved tissue barriers on chips.

Current organ-on-a-chip (OOC) systems cannot mimic in vivo tissue barriers that feature curved geometries and rhythmic movement. This is due to the lack of a relevant membrane that can reproduce the natural biochemical and physical properties of a basement membrane, especially the characteristic sac-like structure possessed by multiple tissue barriers. To address this challenge, a sac-like hydrogel membrane is fabricated here using a one-step simple methodology inspired by soap bubble formation. Di-acrylated Pluronic® F127 (F127-DA) is a hydrogel that exhibits excellent mechanical properties, stably withstanding rhythmic mechanical stretching and fluid flow for at least 24 h. Using this hydrogel to make a membrane, a complex lung-on-a-chip device is successfully constructed, effectively replicating the alveolar-capillary barrier and demonstrating cellular function under physiological respiratory conditions. This membrane offers a crucial platform for replicating sac-like tissue barriers.

A microfluidic lung-on-a-chip based on biomimetic hydrogel membrane.

Lung-on-chips have showed great promise as a tool to recapitulate the respiratory system for investigation of lung diseases in the past decade. However, the commonly applied artificial elastic membrane (e.g., polydimethylsiloxane, PDMS) in the chip failed to mimic the alveolar basal membrane in the composition and mechanical properties. Here we replaced the PDMS film by a thin, biocompatible, soft, and stretchable membrane based on F127-DA hydrogel that well approached to the composition and stiffness of extracellular matrix in human alveoli for construction of lung-on-a-chip. This chip well reconstructed the mechanical microenvironments in alveoli so that the epithelial/endothelial functions were highly expressed with a well established alveolar-capillary barrier. In opposite to the unexpectedly accelerated fibrotic process on the PDMS-based lung-on-a-chip, HPAEpiCs on hydrogel-based chip only presented fibrosis under nonphysiologically high strain, well reflecting the features of pulmonary fibrosis in vivo. This physiologically relevant lung-on-a-chip would be an ideal model in investigation of lung diseases and for development of antifibrosis drugs.

One-pot, self-catalyzed synthesis of self-adherent hydrogels for photo-thermal, antimicrobial wound treatment.

Self-adhering hydrogels are promising materials to be employed as wound dressings, because they can be used for wound healing without the necessity of additional stitching. However, micro-organisms can easily adhere to these hydrogels as well, which usually causes wound infections. Therefore, adhesive hydrogels are often combined with antibiotics. However, this introduces a risk of drug resistance, cytotoxicity and poor cell affinity. Consequently, recently, there has been great interest in developing non-antibiotic, antibacterial adhesive hydrogels. In this article, we present a simple one-pot synthesis procedure to prepare self-adhesive hydrogels composed of poly(acrylamide) (PAM), naturally derived chitosan (CS) and tannic acid/ferric ion chelates (TA@Fe3+). TA@Fe3+ enables self-catalysis of the polymerization reaction. In addition, due to its near infrared (NIR) photothermal responsiveness, TA@Fe3+ allows for eliminating the bacterial activity with up to 91.6% and 94.7% effectivity against Escherichia coli and Staphylococcus aureus, respectively. Mechanical and adhesion testing shows that the hydrogels are tough as well as flexible and will adhere repeatedly to many types of biological tissues, which can be attributed to the combination of physical and chemical bonding between TA@Fe3+ and PAM and CS, respectively. Moreover, in vitro and in vivo tests indicate that the NIR photothermally active hydrogel can effectively prevent bacterial infection and accelerate tissue regeneration, which demonstrates that these hydrogels are promising functional materials for wound healing applications.