Drug/ion co-delivery multi-functional nanocarrier to regenerate infected tissue defect

Abstract

Regeneration of infected tissues is a globally challenging issue in medicine and dentistry. Common clinical therapies involving a complete removal of infected areas together with a treatment of antimicrobial drugs are often suboptimal. Biomaterials with anti-bacterial and pro-regenerative potential can offer a solution to this. Here we design a novel nanocarrier based on a mesoporous silicate-calcium glass by doping with Ag ions and simultaneously loading antimicrobial drugs onto mesopores. The nanocarriers could controllably release multiple ions (silver, calcium, and silicate) and drugs (tetracycline or chlorohexidine) to levels therapeutically relevant, and effectively internalize to human dental stem cells (∼90%) with excellent viability, ultimately stimulating odontogenic differentiation. The release of Ag ions had profound effects on most oral bacteria species through a membrane rupture, and the antibiotic delivery complemented the antibacterial functions by inhibiting protein synthesis. Of note, the nanocarriers easily anchored to bacteria membrane helping the delivery of molecules to an intra-bacterial space. When administered to an infected dentin-pulp defect in rats, the therapeutic nanocarriers effectively regenerated tissues following a complete bacterial killing. This novel concept of multiple-delivering ions and drug can be extensively applied to other infectious tissues that require relayed biological functions (anti-bacterial then pro-regenerative) for successful healing.

Keywords: Anti-bacterial; Co-delivery; Infected tissue; Multi-functional; Tissue regeneration.