Bimetallic MOF/3D exosomes-loaded gelatin-dialdehyde starch hydrogel coating: Multimodal regulation of the bone-implant interface

The GD/MOF@3DE composite enabled pH-responsive release of Zn 2+ , Co 2+ , and 3DExos. • Zn 2+ and Co 2+ provided antibacterial/anti-inflammatory and antioxidant/pro-angiogenic effects, respectively. • Released 3DExos promoted M2 macrophage polarization and directly stimulated osteogenesis. • Transcriptomics revealed enhanced osteogenesis via ECM/HIF-1 pathway regulation. • The multifunctional coating promoted infected bone repair and implant integration in vivo . The compromised bone-implant interface microenvironment, regulated by oxidative stress, infection, inflammation, and disrupted bone homeostasis, remains the core challenge for effective titanium-bone integration. To address these issues, a composite hydrogel coating was fabricated on the titanium substrate, which consisted of a dual-network hydrogel based on a bimetallic metal-organic framework (Zn/Co-MOF) and incorporated gelatin methacryloyl-dialdehyde starch (GelMA-DAS, GD) co-loaded with human umbilical cord mesenchymal stem cell-derived three-dimensional exosomes (hUCMSC-3DExos, 3DE). The resulting GD/MOF@3DE coating exhibited infection-responsive (low-pH) behavior, enabling on-demand release of Zn, Co, and 3DExos. In vitro , the coated titanium effectively scavenged excess intracellular ROS and improved mitochondrial function. It also demonstrated potent anti-inflammatory activity by promoting macrophage polarization toward the M2 phenotype. The modified substrate showed excellent biocompatibility, broad-spectrum antibacterial efficacy against Gram-positive and Gram-negative pathogens, and significant upregulation of osteogenic markers. Transcriptomic analysis revealed that osteogenesis was promoted through regulation of key pathways, including extracellular matrix organization and HIF-1 signaling. Moreover, the coating displayed pronounced angiogenic and immunomodulatory osteogenic potential. Subcutaneous infection models and femoral defect repair experiments confirmed that this multifunctional coating possesses outstanding anti-infective, antioxidative, anti-inflammatory, angiogenic, and osseointegrative properties, offering an innovative strategy for modulating the postoperative microenvironment around orthopedic implants.