Tetrahedral DNA Nanostructure‐Modified Nanocoating for Improved Bioaffinity and Osseointegration of Titanium

Abstract Titanium (Ti) is extensively used in the medical field because of its excellent biomechanical properties; however, how to precisely fabricate Ti surfaces at a nanoscale remains challenging. In this study, a DNA nanocoating system to functionalize Ti surfaces via a series of sequential reactions involving hydroxylation, silanization, and click chemistry is developed. Tetrahedral DNA nanostructures (TDNs) of two different sizes (≈7 and 30 nm) are assembled and characterized for subsequent surface attachment. In vitro and in vivo assays demonstrated significantly enhanced cell adhesion, spreading, proliferation, osteogenesis, and osseointegration on Ti surfaces modified with 30‐nm TDNs, compared to slightly improved effects with 7‐nm TDNs. Mechanistic studies showed that the focal adhesion pathway contributed to the enhanced bioaffinity of the 30‐nm TDNs, as evidenced by the upregulated expression of vinculin and activation of the Akt signaling pathway. Moreover, under inflammatory or hypoxic conditions, Ti surfaces modified with 30‐nm TDNs maintained excellent cellular performance comparable to that under normal conditions, suggesting a broader adaptability for DNA nanoparticles. Thus, better performance is achieved following modification with 30‐nm TDNs. In summary, the proposed DNA‐guided nanocoating system provides a novel and efficient strategy for the surface nanofabrication of Ti.