Drug-Loaded Metal-Organic Gel Coating On Biodegradable Zinc For Bone Implants Application

Zn has been regarded as the most promising biodegradable metal for bone implants due to its moderate degradation rate and potential biological functions.However,the insufficient corrosion behavior(uneven corrosion model,excessive Zn²⁺release,etc)and lack of biological functions（pro-osteogenesis,anti-inflammatory,antibacterial）of Zn have limited its clinical application.In response to this,a drug-loaded metal-organic gel coating was designed in our study,which was formed by the coordination chelation of Zn²⁺with carboxymethyl chitosan（CMC）and gelatin（Gel）and loaded aspirin（ASA）in site.The surface morphology observation proved that the coating is dense and stable,and the density of the coating was positively correlated with the concentration of ASA.FT-IR and XPS tests confirmed the loading of ASA and the bonding of Zn²⁺with organic components in the coating.The water contact angle test showed that the modified Zn surface has higher hydrophilicity and surface energy than the unmodified Zn.Electrochemical and degradation tests showed that after modification,the corrosion current density of Zn decreased by 90%compared with that before modification,indicating that the coating effectively slowed down the corrosion of the Zn substrate.Long-term immersion experiments showed that the coating could reduce the release of Zn²⁺,the morphology observation after corrosion degradation indicated that the coating could inhibit the localized corrosion of Zn substrate.Calcium phosphate precipitation and alizarin red staining experiments demonstrated that the coating could promote the precipitation of calcium phosphate and the formation of calcium nodules.In vitro pre-osteoblast culture experiments and alkaline phosphatase activity experiments demonstrated that the modified Zn could promote the proliferation and differentiation of osteoblasts more than unmodified Zn.The macrophage culture experiment and the inflammatory factor test experiment showed that after the coating was covered,the number of macrophage adhesion on the Zn surface decreased by 60%;the concentration of pro-inflammatory factors in the culture medium decreased,and the concentration of anti-inflammatory factors increased.The culture experiments of Staphylococcus aureus and Escherichia coli showed that the coating had an excellent antibacterial ability,and the antibacterial rate is high as 95%.The surface bacterial morphology observation experiment proved that the modified Zn surface had less bacterial adhesion than the unmodified Zn.Theoretical analysis shows that with the increase of ASA content in the coating,more ASA bonds with Zn²⁺in the pores of the gel network,more network pores are filled,and the density of the coating increase.The dense and uniform structure of the coating and the lower corrosion potential than that of the Zn can provide corrosion protection for the Zn substrate from the perspective of kinetic and thermodynamics.The chelation of Zn²⁺by organic components in the coating reduces the release of Zn²⁺and slows down the Zn substrate degradation.The stable and uniform structure of the coating contributes to the uniform growth of corrosion products,thereby inhibiting localized corrosion of the Zn substrate.The chelation of calcium and phosphorus salts by components in the coating and the higher surface energy of the coating enhances the osteocompatibility of the modified Zn.The release and degradation of the appropriate amount of ASA,Zn²⁺,CMC,and Gel in the coating can promote the growth and differentiation of osteoblasts,reduce the adhesion of macrophages,regulate the concentration of inflammatory factors and inhibit the growth of bacteria.In summary,our study proposes a surface modification strategy that effectively improves the corrosion resistance of Zn,inhibits the local corrosion model,controls the release of Zn²⁺,as well as strengthens the ability of osteogenesis,anti-inflammatory,and antibacterial ability of Zn.That makes Zn better used in the field of bone implants.