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

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Microfluidics

Background:

• Cold exposure causes vasoconstriction, leading to chilblains and hypothermia.
• Existing animal models and in vitro systems poorly replicate cold-induced vascular injury.
• Current vascular chips lack temperature responsiveness, limiting simulation of cold stress.

Purpose of the Study:

• To develop a novel, temperature-responsive "vessel-on-a-chip" model.
• To simulate cold-induced vasoconstriction and endothelial cell injury.
• To provide a platform for studying cold-related cardiovascular diseases and drug screening.

Main Methods:

• Fabricated a microfluidic bioreactor by grafting a thermosensitive hydrogel (N-isopropyl acrylamide and gelatin methacrylamide) onto polydimethylsiloxane.
• The hydrogel's lower critical solution temperature was set at 30°C for temperature-dependent swelling.
• Cultured endothelial cells on the hydrogel surface within the microchannel and applied perfusion for physiological shear stress.

Main Results:

• The thermosensitive hydrogel mimicked in vivo blood stasis by swelling at low temperatures (4°C), reducing channel flow rate by 10%.
• Cold stimulation induced endothelial cell necrosis, mitochondrial membrane potential collapse, cytoskeleton disaggregation, and increased reactive oxygen species.
• Static endothelial cell cultures showed limited response to cold exposure compared to the perfused chip.

Conclusions:

• The developed thermosensitive vessel-on-a-chip accurately replicates cold-induced endothelial injury.
• This technology offers a significant advancement for studying the pathogenesis of cold-induced cardiovascular diseases.
• The model provides a promising platform for therapeutic drug screening for conditions like chilblains and hypothermia.