Engineered Metallic Ion-Based Hydrogel for Tendon-Bone Reconstruction

Rotator cuff regeneration is hindered by compromised vascular architecture, inflammation, and instability of the reconstructed tendon-bone interface. Herein, inspired by the phenomenon of magnetic clasps being connected together by a specific structure, an engineered metallic ion-based hydrogel scaffold was constructed through a bioorthogonal click reaction between (DOPA)₄-PEG₅-N₃ and DBCO-BMP-2 peptides and a photopolymerization process in the hydrogel matrix, exhibiting the potential for angiogenesis, bone regeneration, and modulation of the inflammatory milieu, which aimed at facilitating rotator cuff regeneration. In vitro studies showed that the composite hydrogel scaffold stimulated the angiogenic activity of human umbilical vein endothelial cells and osteogenic differentiation of bone marrow mesenchymal stem cells, transforming macrophages from M1 to M2. Moreover, imaging and immunohistochemical analysis of a rat rotator cuff injury models demonstrated that the composite hydrogel could effectively promote regeneration and exhibit remarkable biocompatibility. In summary, this composite hydrogel material established an effective platform for the release of metal ions and clickable peptides, which accelerated the regeneration of rotator cuff injuries and had broad prospects for application in rotator cuff therapy.