Tracking <i>in vitro</i> biodegradation dynamics in cartilage tissue engineering using dual-labeled hydrogel/scaffold composites

This study addresses the challenges of tracking cell-mediated biodegradation in cartilage tissue engineering, where hydrogels and scaffolds play a crucial role in providing structural support and promoting tissue regeneration. This research area has been rarely studied, offering potential insights into bridging the gap between<i>in vitro</i>and<i>in vivo</i>conditions for real-time monitoring of tissue regeneration alongside biodegradation. We developed dual-labeled hydrogel/scaffold composites for real-time monitoring of scaffold degradation in response to cell activity. Gelatin methacryloyl (GelMA) hydrogels are extensively explored for cartilage tissue engineering, albeit concerns remain regarding their mechanical properties under load-bearing conditions. To address this, a hydrogel/scaffold composite system was employed in this study, where a poly (<i>ϵ</i>-caprolactone) (PCL) hex prism edge structure acts as a scaffold to support the cell-laden GelMA hydrogel. Fluorophore labeling of GelMA and PCL facilitated non-invasive monitoring of the hydrogel/scaffold composite biodegradation under cell proliferation conditions. Initially, the behavior of fluorescent-tagged Hydrogel/Scaffold was examined under accelerated degradation conditions. Subsequently, human adipose-derived mesenchymal stem cells loaded into fluorescent-labeled hydrogel/scaffolds were evaluated for their biocompatibility potential and chondrogenesis. Results demonstrated a correlation between the loss of fluorescence from the hydrogel/scaffold degradation, accompanied by extracellular matrix accumulation. The fluorescently labeled hydrogel/scaffold holds promising application for cartilage tissue engineering, offering the capability to monitor biodegradation using high-throughput and contactless techniques.