Development of mesoporous bioactive glass‐containing macroporous titanium for controlled release of antimicrobial drugs

Abstract

Biofilm-associated infections pose a serious threat to the long-term survival of metal-based bone implants, which can potentially be resolved by the controlled delivery of antimicrobial agents locally at the implant surface. Mesoporous bioactive glasses (BAGs) are multifunctional materials able to combine bone-bonding properties with such a drug release functionality. Here, we propose for the first time to modify a macroporous Ti implant material with an antimicrobial-releasing BAG phase. The feasibility of a sol-gel synthesis route, including the structure-directing agent (SDA) Pluronic F127, and its effect on the mesoporous structure and concomitant drug release performance was evaluated. Mesopore sizes ranged from 3.4 nm for SDA-free to 3.7 nm for SDA-derived BAG, thereby both enabling configurational diffusion of the antiseptic chlorhexidine (CHX), but the latter showed a more narrow pore size distribution leading to a slower, more controlled release. Adjusting the feed concentration allowed fine-tuning the daily CHX release through the SDA-derived Ti/BAG composite to 1.4 μM. Even though just below the biofilm inhibitory concentration, this daily release rate was sufficient to effectively prevent Streptococcus mutans biofilm formation on the surface of the material. This proof-of-concept for a temporary antimicrobial-releasing bioceramic surface modification on Ti can be of interest for orthopedic implants.

pH-Triggered Controlled Release of Chlorhexidine Using Chitosan-Coated Titanium Silica Composite for Dental Infection Prevention

“…Systemic administration of antibiotics for the treatment of these infections is less effective and not sufficient to completely eradicate the formation of biofilm from the surface of implants as the resistance of bacteria inside a biofilm is a thousand-fold higher than planktonic bacteria [ 33 ]. Through our previous research and other works, it has been proven that localized drug delivery is more effective against the formation/treatment of a bacterial biofilm on an implant surface compared to systemic drug delivery [ 13 , 14 , 34 , 35 , 36 ]. It is possible to control the rate of drug release by varying the concentration of the feed solution and the pore size of the silica diffusion barrier [ 14 ].…”

Biomaterial strategies to combat implant infections: new perspectives to old challenges

“…The latter is especially problematic in case of antimicrobial therapy as the exposure of microorganisms to sub-inhibitory concentrations, before biofilm eradication can lead to re-infection and AMR development. Recently, a drug-releasing Ti/BG system was reported by Kamarudin et al, where a mesoporous BG, contained within a microporous Ti structure, acted as a barrier for a more controlled release of chlorhexidine, an antiseptic used for treatment of peri-implantitis around dental implants [243]. In combination with a refillable internal reservoir, this composite allows fine-tuning the release of antimicrobial agents to therapeutic concentrations, i.e.…”