Dynamic Col-HZ Hydrogel with Efficient Delivery of Bioactivator Promotes ECM Deposition and Cartilage Formation

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.