Abstract: BACKGROUND: The long-term stability of percutaneous titanium implants is compromised by the lack of dynamic integration mechanisms at the skin-implant interface. Persistent challenges include barrier function deterioration and secondary infections due to epidermal downgrowth, which severely restrict clinical utility. Although titanium surface modifications have significantly enhanced osseointegration, the biological regulation of the skin tissue interface is still challenging.
OBJECTIVE: To develop a biomimetic functional coating based on titanium-affinity peptide and improve titanium implant-skin tissue interface integration. 
METHODS: Pure titanium sheets were treated with acid and base by an acid-base two-step method, and then immersed in a titanium affinity peptide solution modified with arginine-glycine-aspartic acid sequence to prepare a bionic coating on the surface of titanium sheets. The protein adsorption and release on the surfaces of acid-base treated titanium sheets and bionic coating modified titanium sheets were detected. The acid-base treated titanium sheets and bionic coating modified titanium sheets were co-cultured with Staphylococcus aureus, respectively. The adhesion was observed by scanning electron microscopy. The bacterial survival was detected by live/dead staining. The acid-base treated titanium sheet and the biomimetic coating modified titanium sheet were co-cultured with mouse fibroblasts, respectively. The proliferation was detected by CCK-8 assay. Cell adhesion was detected by phalloidin staining. Cell migration was detected by scratch test. Type I collagen and transforming growth factor β expression levels were detected by immunofluorescence staining. Type I and type III collagen levels in cell supernatant were detected by ELISA. Type I collagen, type III collagen, transforming growth factor β, α-smooth muscle actin and vascular endothelial growth factor mRNA expression levels were detected by qRT-PCR.
RESULTS AND CONCLUSION: (1) The bionic coating modified titanium sheet showed significant advantages in protein adsorption kinetics: Compared with the acid-base treated titanium sheet, the protein adsorption rate on the surface of the bionic coating modified titanium sheet fluctuated less within 60 minutes, and the protein release rate in PBS was relatively stable, and the binding with protein was more firmly. (2) Scanning electron microscopy showed that a certain amount of bacteria adhered to the surfaces of both groups of titanium sheets, and the bacterial morphology was relatively complete and spherical, but live-dead staining showed that the bacterial survival rate on the surface of the bionic coating modified titanium sheet was lower. (3) Mouse fibroblasts could proliferate, adhere and spread on the surfaces of both groups of titanium sheets, among which the bionic coating modified titanium sheet could promote the migration of mouse fibroblasts. Immunofluorescence staining showed that the two groups of titanium sheets could promote the expression of type I collagen and transforming growth factor β. ELISA results showed that the bionic coating modified titanium sheet could delay the premature deposition of type I collagen. qRT-PCR results showed that the bionic coating modified titanium sheet could increase the mRNA expression of type III collagen and transforming growth factor β. (4) These findings show that bionic coating modification can improve the stability of protein adsorption and release on the surface of titanium sheets, effectively inhibit bacterial adhesion and proliferation, and promote the migration of fibroblasts and the expression of factors related to wound repair.

Key words: percutaneous titanium implant, titanium affinity peptide, bionic coating, surface modification, bio-sealing, interfacial integration, antimicrobial property, tissue repair