Abstract
Efforts in cartilage tissue engineering to repair injuries have seen limited success, primarily due to the inability of scaffold materials to establish a microenvironment conducive to extracellular matrix (ECM) deposition by chondrocytes. Hydrogels, which mimic human tissue, are commonly employed as scaffold materials; however, their constrained network structure and low bioactivity impede chondrocyte ECM deposition, complicating cartilage repair. In this study, we developed dynamic Col-HZ hydrogels featuring adaptive networks by forming hydrazone (HZ) bonds between bioactive natural collagen and synthetic polyethylene glycol (PEG). In contrast to static hydrogels that rely on covalent bonds, Col-HZ dynamic hydrogels facilitate chondrocyte migration and ECM deposition. Additionally, the aldehyde groups on the Col-HZ hydrogel scaffold can engage in dynamic Schiff base bonding with amine groups. Leveraging this non-covalent interaction, we incorporated the bioactivator TD-198946, known to enhance ECM synthesis, into the Col-HZ hydrogel. This significantly boosted ECM deposition and reduced inflammation. Transcriptomic sequencing and bioinformatics analyses indicate that both the dynamic network of the hydrogel and the binding of TD-198946 promote cartilage ECM deposition through modulation of the Wnt/β-catenin signaling pathway. Consequently, the Col-HZ dynamic hydrogel, in combination with TD-198946, creates an improved microenvironment that supports ECM deposition and facilitates cartilage tissue formation.