Anti-Periprosthetic Infection Strategies: From Implant Surface Topographical Engineering to Smart Drug-Releasing Coatings

Abstract

Despite advanced implant sterilization and aseptic surgical techniques, periprosthetic bacterial infection remains a major challenge for orthopedic and dental implants. Bacterial colonization/biofilm formation around implants and their invasion into the dense skeletal tissue matrices are difficult to treat and could lead to implant failure and osteomyelitis. These complications require major revision surgeries and extended antibiotic therapies that are associated with high treatment cost, morbidity, and even mortality. Effective preventative measures mitigating risks for implant-related infections are thus in dire need. This review focuses on recent developments of anti-periprosthetic infection strategies aimed at either reducing bacterial adhesion, colonization, and biofilm formation or killing bacteria directly in contact with and/or in the vicinity of implants. These goals are accomplished through antifouling, quorum-sensing interfering, or bactericidal implant surface topographical engineering or surface coatings through chemical modifications. Surface topographical engineering of lotus leaf mimicking super-hydrophobic antifouling features and cicada wing-mimicking, bacterium-piercing nanopillars are both presented. Conventional physical coating/passive release of bactericidal agents is contrasted with their covalent tethering to implant surfaces through either stable linkages or linkages labile to bacterial enzyme cleavage or environmental perturbations. Pros and cons of these emerging anti-periprosthetic infection approaches are discussed in terms of their safety, efficacy, and translational potentials.

Keywords: antifouling coatings; bactericidal coatings; implant surface modifications; implant-related infections; surface topography.

Figure 1.

(A) Anti-fouling or QS-interfering surface modification strategies designed to inhibit bacterial adhesion, colonization and biofilm formation. These strategies involve coating surfaces with hydrophilic polymers, engineering superhydrophobic nanostructured surface topography to emulates the lotus leaf effect or applying coatings that releases agents interfering QS. (B) Bactericidal surface modification strategies designed to kill bacteria in direct contact with the surface and/or those in its vicinity. These strategies involve engineering nanostructured surface topography capable of physically rupturing bacteria, covalently tethering bactericidal agents to the surface with stable linkages or linkages labile to bacterial enzyme cleavage or pH perturbations, physically encapsulating bactericidal agents in surface coatings for passive releases, or applying photothermal/photodynamic responsive coatings (e.g. in response to near-infrared, or NIR, irradiation) designed to destruct established biofilms.

Figure 2.

SEM images of bacteria colonies after 2h on (A) NT, (B) NTS, and (C) TiS, and after 4h (D) NT, (E) NTS, and (F) TiS (×10K). Reproduced with the permission from ref . Copyright 2011 Hindawi.

Figure 3.

pSBMA grafted from the surface of Ti6Al4V IM pins combined with a single vancomycin injection (Ti-pSBMA+VAN) more effectively suppressed S. aureus periprosthetic infection in mouse femoral canals than pSMBA coating alone (Ti-pSBMA) or the single systemic vancomycin injection alone (Ti6Al4V+VAN). (a) μ-CT axial view of the femur at day 21 (pins contoured out). (b) μ-CT quantitation of bone volume fraction (BVF), bone mineral density (BMD) and cortical thickness (C. Th) at day 21. *P<0.05, **P<0.01, ***P<0.001. All femurs were inoculated with 40-CFU Xen 29 prior to pin insertion. Reproduced with the permission from ref . Copyright 2020 American Chemical Society.

Figure 4.

(A-D) SEM and fluorescence images of S. aureus attached for 24 h on the control (top) and black titanium (bottom) surfaces. Insets in panels A and C: enlarged views of live and dead bacteria on the respective surfaces. Reproduced with the permission from ref . Copyright 2017 Springer Nature.

Figure 5.

Schematic illustration of possible antibacterial mechanisms on the surface of Ti6Al4V5Cu implants. Ti6Al4V5Cu releases Cu ions. The released Cu ions could accumulate in the cell membrane affecting membrane permeability, disrupt the activity of respiratory chain, enter bacterial cells to generate ROS, and disrupt the gene replication of S. aureus. Reproduced with the permission from ref . Copyright 2015 Wiley Publication.

Figure 6

(a) IVIS images of mouse femurs injected with 40 CFU Xen-29 S. aureus and inserted with IM pins with PEGDMA-Oligo-Vanco or PEGDMA-Oligo coatings at 2, 7, 14, and 21 days. (b) Quantification of longitudinal bioluminescence signals of mouse femurs injected with 40 CFU Xen-29 S. aureus and inserted with the different hydrogel-coated pins at 2, 7, 14, and 21 days (n = 14). (c) S. aureus recovery from explanted pins at 21 days (n = 11). (d) 3D μCT axial images of the distal femoral region 21 days after the insertion of Ti6Al4V IM pins (pins excluded during contouring) with different hydrogel coatings, with or without the inoculation of 40-CFU Xen-29 S. aureus. Error bars represent standard deviations. * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001 (two-way ANOVA for part b; Student’s t-test for part c). Reproduced with the permission from ref . Copyright 2019 American Chemical Society.