<i>In vivo</i> dynamic visualization and evaluation of collagen degradation utilizing NIR-II fluorescence imaging in mice models

Collagen-based biomaterials are gaining prominence in tissue engineering, attributed to their remarkable biocompatibility, inherent biodegradability, and unparalleled capacity to facilitate tissue repair and regeneration. However, the ability to dynamically visualize and quantitatively assess collagen degradation <i>in vivo</i> remains a critical challenge, hindering the development of optimized biomaterials for clinical applications. To address this, a novel approach was developed to monitor the injury microenvironment by conjugating second near-infrared quantum dots with solid collagen. This live imaging system offered high-resolution, real-time tracking of collagen degradation both <i>in vitro</i> and <i>in vivo</i>, enabling a deeper understanding of the degradation behavior under various conditions. This system was applied to mouse models with different cartilage defects, including critical-sized defect (CSD), minor defect (Minor) and sham surgery (Sham) groups for a 28-day <i>in vivo</i> monitoring. Among them, the CSD group exhibited the fastest and most stable collagen degradation, indicating that the degradation rate was closely linked to the severity of the injury. Transcriptomic analysis further identified key signaling pathways that might drive rapid collagen degradation by promoting collagenase activity and tissue remodeling in cartilage defect conditions. In summary, our study provided valuable insights into the mechanisms of collagen degradation under different injury conditions, contributing to innovative strategies for designing collagen-related biomaterials in the future.