期刊
ACS NANO
卷 17, 期 16, 页码 15942-15961出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.3c04049
关键词
osteoporotic bone repair; ROS-responsive coating; titanium; rolling circle amplification; TypeH vessels
A nanoengineered composite coating was developed to improve the in situ osseointegration of a Ti implant for osteoporotic fracture repair. The coating inhibited STING in endothelial cells to stimulate the formation of Type H vessels. Galvanotaxis recruited endothelial cells and mesenchymal stem cells to the implant surface, where released narigenin upregulated eNOS in recruited endothelial cells under ROS stimulation, leading to enhanced local angiogenesis. Coordinately released DNFzns abolished STING expression in endothelial cells to transform the newly formed vessels into Type H vessels, thereby promoting the osseointegration of Ti implants.
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.
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