DNAzyme Nanoconstruct-Integrated Autonomously-Adaptive Coatings Enhance Titanium-Implant Osteointegration by Cooperative Angiogenesis and Vessel Remodeling

Orthopedic implants have a high failure rate due to insufficientinterfacial osseointegration, especially under osteoporotic conditions.Type H vessels are CD31(+)EMCN(+) capillaries withcrucial roles in mediating new bone formation, but their abundancein osteoporotic fracture site is highly limited. Herein, we reporta nanoengineered composite coating to improve the in situ osseointegrationof a Ti implant for osteoporotic fracture repair, which is realizedthrough inhibiting the stimulator of interferon genes (STING) in endothelialcells (ECs) to stimulate type H vessel formation. Autonomously catalyticDNAzyme-ZnO nanoflowers (DNFzns) were prepared through rolling circleamplification (RCA) of STING mRNA-degrading DNAzymes, which were thenintegrated on the Ti surface and further sequentially complexed withthioketal-bridged polydopamine and naringenin (Ti/DNFzn/PDA-Nar).ECs and mesenchymal stem cells (MSCs) can be recruited to the implantsurface by galvanotaxis, accounting for the negative charges of DNFzn/PDA-Nar,subsequently released Nar under reactive oxygen species (ROS) stimulationto upregulate endothelial nitric oxide synthase (eNOS) in recruitedECs, leading to enhanced local angiogenesis. Meanwhile, the coordinatelyreleased DNFzns would abolish STING expression in ECs to transformthe newly formed vessels into Type H vessels, thus substantially promotingthe osseointegration of Ti implants. This study provides applicationprospects for improving implant osteointegration for osteoporoticfracture treatment.