Silane-coupled chitosan-cyclodextrin/rosmarinic acid-zinc complex coating improves the osseointegration of titanium implants in high-glucose environments

Abstract

The osseointegration of titanium implants in a diabetic microenvironment is greatly limited by mitochondrial dysfunction, increased reactive oxygen species, and reduced osteoblastic activity. Rosmarinic acid (RA), a polyphenolic molecule with powerful antioxidant and anti-inflammatory properties, can chelate Zn ions to form the RA-Zn complex. This study aimed to develop a local drug delivery system on the titanium surface using this complex. Carboxymethyl-β-cyclodextrin and chitosan were used to encapsulate the complex, and the coupling agent silane triethoxysilylpropyl succinic anhydride was used to covalently immobilize the chitosan molecules after binding to the alkali-heat treated titanium surface. A coating with good hydrophilic properties, adhesive strength, and frictional resistance, which allowed for the controlled and sustained release of RA-Zn, was successfully constructed. The coating had good biocompatibility and promoted the adhesion and proliferation of mouse preosteoblasts (MC3T3-E1) under high-glucose conditions. It upregulated the expression levels of osteogenic genes, increased the secretion of osteogenic-related proteins, and promoted cell mineralization. Furthermore, it improved the mitochondrial dynamics and restored mitochondrial dysfunction under high-glucose conditions. This study proposes a new titanium implant surface modification strategy to deliver biological components with antioxidant and osteogenic activities to target sites.