Injectable and Tissue Adhesive Chitosan/Hyaluronic Acid–Based Hydrogels for Stem Cell Delivery and Cartilage Regeneration

Current therapeutic approaches for knee osteoarthritis (KOA) focus on symptom relief rather than addressing articular cartilage degeneration. Stem cell therapy holds promise for enhancing KOA treatment by promoting tissue regeneration, yet challenges remain in achieving minimally invasive delivery with sustained cell retention and viability. This study introduces an in situ fabricated, biodegradable, injectable, self-healing, tissue-adhesive hydrogel (Ald-HA/Dopa-HBCS). Formed by coinjecting two polymer solutions, it features a uniform, porous 3D structure, ideal for low-trauma administration and supporting human adipose-derived stem cells (hADSCs). We engineered its mechanical properties, gelation time, and degradation rate by adjusting polymer concentrations and ratios, ensuring hADSC viability for at least 14 days postinjection. Catechol groups provide tissue adhesion, enhancing therapeutic potential by retaining hADSCs at defect sites. The hydrogel also preserves chondrogenic gene expression and protein production in hADSCs, indicating broader applications beyond cartilage repair, extending to diverse cell-based therapies.