Drug Release from Thermo‐Responsive Polymer Brush Coatings to Control Bacterial Colonization and Biofilm Growth on Titanium Implants

Abstract

Despite decades of biomedical advances, the colonization of implant devices with bacterial biofilms is still a leading cause of implant failure. Clearly, new strategies and materials that suppress both initial and later stage bacterial colonization are required in this context. Ideal would be the implementation of a bactericidal functionality in the implants that is temporally and spatially triggered in an autonomous fashion at the infection site. Herein, the fabrication and validation of functional titanium-based implants with triggered antibiotic release function afforded via an intelligent polymer coating is reported. In particular, thermo-responsive poly(di(ethylene glycol) methyl ether methacrylate) (PDEGMA) brushes on titanium implants synthesized via a surface-initiated atom transfer radical polymerization with activators regenerated through the electron transfer technique (ARGET ATRP) allows for a controlled and thermally triggered release of the antibiotic levofloxacin at the wound site. Antibiotic loaded brushes are investigated as a function of thickness, loading capacity for antibiotics, and temperature. At temperatures of the infection site >37°C the lower critical solution temperature behavior of the brushes afforded the triggered release. Hence, in addition to the known antifouling effects, the PDEGMA coating ensured enhanced bactericidal effects, as demonstrated in initial in vivo tests with rodents infected with Staphylococcus aureus.

Stimuli‐Responsive Antibacterial Materials: Molecular Structures, Design Principles, and Biomedical Applications

“…By adjusting the content and length of OEGMA chains, the average collapse temperature of these brushes can be successfully turned from 22 to 40 ℃. [ 35 ] Besides, Pluronic F127 (PF127, also known as Poloxamer 407) is a thermo‐responsive gel that presents gelling property and proper sol‐gel transition temperature (Figure 1A ). Along with the temperature rise, PF127 micelles form a gel.…”

Toward Bactericidal Enhancement of Additively Manufactured Titanium Implants

“…In recent years, intelligent antimicrobial coatings have gradually emerged [148]. When the implant is invaded by bacteria and IAIs occurs, it is stimulated by temperature [149], pH [150], and electrical signals [151] to release antibiotics. Thus, the unnecessary release of antimicrobial agents in the uninfected state is avoided, and the risk of bacterial resistance is minimized.…”

Synthetic strategies to enhance the long-term stability of polymer brush coatings

“…chameleons. 20 Next to these bioinspired approaches, brushes can also be applied in smart adhesives, 21,22 energy devices, 23,24 bactericidal [25][26][27] and blood compatible 28,29 coatings, membranes, 30,31 nano-theranostics, 32 times the radius of gyration, the polymers do not interact and form mushrooms in good solvents. When these low-density polymers are in a poor solvent and/or strongly interacting with the substrate, pancakes instead of mushrooms are formed.…”

“…chameleons. 20 Next to these bioinspired approaches, brushes can also be applied in smart adhesives, 21,22 energy devices, 23,24 bactericidal [25][26][27] and blood compatible 28,29 coatings, membranes, 30,31 nano-theranostics, 32 sensing [33][34][35] and many more applications. [36][37][38][39] End-anchored polymers can adopt different conformations.…”