A cartilage-on-a-chip for recapitulating cell microenvironment and real-time nitric oxide monitoring

Chondrocytes, the cells that formulate the cartilage, reside in a complex microenvironment composed of extracellular matrix (ECM) and biomechanical factors. Although current cartilage models can reproduce the ECM architecture or mechanical environment, they fail to provide the transient biochemical information of chondrocytes during dynamic mechanical loading. Here, we present a cartilage-on-a-chip integrated with a stretchable electrochemical sensor, which consists of collagen-alginate hybrid hydrogel to mimic ECM-like matrices and a pneumatic actuation unit to apply controllable mechanical compression to cell-laden hydrogel. The built-in stretchable electrochemical sensor allows real-time monitoring of nitric oxide (NO) release from chondrocytes when subjected to physiological and hyperphysiological compression. This device enables the establishment of a reliable cartilage model and the assessment of the biochemical response, providing an evaluation platform for cell regulation, tissue engineering, and drug screening.