Adhesive hydrogel-enabled integrative fixation for cartilage and osteochondral repair

Secure attachment of repair constructs to native cartilage and underlying bone tissues remains a major unmet need in chondral and osteochondral surgery. Currently existing injectable or scaffold-based cell carriers, while biologically compatible, lack the mechanical integrity and interfacial adhesion. In most cases, a secondary fixation using suturing or fibrin glue remains necessary, which can be challenging in terms of achieving long-term integration and reproducible clinical outcomes. Here, we investigated the biomechanical and adhesive performance of our previously developed photo-curable phosphoserine-functionalized methacrylated gelatin hydrogel, with the aim of defining a clinically relevant formulation window for integrative fixation. Polymer content (PC) was varied to control cohesive and interfacial properties. The hydrogel exhibited tunable biomechanical performance across formulations, with no significant batch-to-batch variability. Autoclave sterilization reduced stiffness and adhesion but preserved overall mechanical integrity, with sterilization before lyophilization (T1) causing smaller performance losses than sterilization after precursor preparation (T2). Ex vivo tensile adhesion on human osteochondral interfaces demonstrated multi-tissue bonding, with the hydrogel achieving several fold higher adhesion than fibrin glue on cartilage, subchondral bone, and cancellous bone. Adhesion was highest on cartilage (68.3 ± 12.5 kPa), followed by subchondral (44 ± 5.5 kPa) and cancellous bone (31.2 ± 8.2 kPa). In human chondral defects, the hydrogel could be injected and photocured under both dry and wet conditions, although surface hydration reduced adhesion by ∼50%, indicating enhanced performance under dry arthroscopy or open conditions. Cancellous bone penetration experiments revealed that lower PC (10 wt%) promotes trabecular infiltration, whereas higher PC (15 wt%) limits penetration and improves defect confinement. Overall, these results identify 15-20 wt% PC as a clinically relevant formulation window, combining injectability, manufacturing reproducibility and autoclave compatibility with robust multi-tissue adhesion. This work supports further development of the hydrogel as a potential integrative fixation strategy for minimally invasive cartilage and osteochondral repair and its future evaluation as a cell-laden delivery matrix in vivo.