From passive loading to network formation: click clotting inspires the next generation of bone repair materials

Developing regenerative materials with high mechanical load-bearing capacity, adaptability to complex defect shapes, and excellent osteoinductive activity remains a long-standing challenge in bone tissue engineering. 1 In traditional construction paradigms, it is difficult to strike a perfect balance between mechanical support and cell affinity, whether for high-strength bioceramics or highly biocompatible hydrogels.In particular, to address the issue of material biocompatibility, researchers typically embed stem cells directly or indirectly (e.g., using nanocarriers) into hydrogels with low cross-linking density.2,3 However, increasing the cell load may disrupt the continuity of the polymer network and weaken the material's initial load-bearing capacity.Conversely, whilst increasing the polymer concentration or crosslinking density can enhance structural stability, it will also limit cell survival, spreading and matrix remodelling.For example, Tian et al. 4 demonstrated that, as cell density increased, the stress-strain curve of