Hyaluronan regulates the assembly structure and biofunction of polycationic silk fibroin to boost microfracture.

Dysregulated inflammatory microenvironment and insufficient recruitment of functional cells/factors at the early stage limit the efficacy of microfracture (MF) therapy. Here, we regulated the assembly structure of functional polycationic silk fibroin (CSF) with sulfhydryl-modified hyaluronan (HS) to fabricate a cartilage repair patch (ECSF-HS-H), which achieved rapid hemostasis, recruitment of reparative cells/factors, and inflammation regulation. Through non-covalent/covalent interactions and β-sheet transitions, the assembly structure of CSF was reconfigured to adapt to the cyclic mechanical properties required under articular stress conditions while preserving inherent rapid hemostatic ability, reduce the potential inhibitory effect of cationic charges on cell proliferation, and enhance chondrogenic differentiation of stem cells. In a rabbit MF model, ECSF-HS-H demonstrated accelerated coagulation, reduced early inflammation in synovial fluid, promoted M2 macrophage polarization, and improved hyaline cartilage regeneration. This strategy of functional structural regulation at the molecular level offers a novel approach for developing protein-based scaffolds to enhance MF procedures.