Antibacterial surface treatment for orthopaedic implants

Abstract

It is expected that the projected increased usage of implantable devices in medicine will result in a natural rise in the number of infections related to these cases. Some patients are unable to autonomously prevent formation of biofilm on implant surfaces. Suppression of the local peri-implant immune response is an important contributory factor. Substantial avascular scar tissue encountered during revision joint replacement surgery places these cases at an especially high risk of periprosthetic joint infection. A critical pathogenic event in the process of biofilm formation is bacterial adhesion. Prevention of biomaterial-associated infections should be concurrently focused on at least two targets: inhibition of biofilm formation and minimizing local immune response suppression. Current knowledge of antimicrobial surface treatments suitable for prevention of prosthetic joint infection is reviewed. Several surface treatment modalities have been proposed. Minimizing bacterial adhesion, biofilm formation inhibition, and bactericidal approaches are discussed. The ultimate anti-infective surface should be "smart" and responsive to even the lowest bacterial load. While research in this field is promising, there appears to be a great discrepancy between proposed and clinically implemented strategies, and there is urgent need for translational science focusing on this topic.

Figure 1

Schematic illustration of the process of biomaterial colonization starting from individual bacteria adhesion across micro-colonies towards formation and maturation of biofilm (1); Bacteria cannot activate the biofilm-related phenotype before they firmly attach to the substrate. After attachment and change in the phenotype they are able to produce the matrix of extracellular polymeric substances that protect them against host immune response and antibiotics. If host cell achieves irreversible attachments on the biomaterial surface first (i.e., if they are the winner) it is difficult for bacterial cells to start with biofilm formation (2); The period before firm attachment and phenotypic change is therefore the window of opportunity for almost all antibiofilm strategies (3). During that time these strategies compete with bacteria for implant surface attachment and microenvironment. ATB = antibiotics.

Figure 2

Ideas of multifunctional surfaces in total hip arthroplasty designed to simultaneously or successively respond to various biological and mechanical tasks. The response depends on the specific abilities of the coatings acquired during the manufacturing process.

Figure 3

The relationship between biomaterial surface roughness/chemistry and bacterial attachment is intricate. Bacterial attachment is facilitated by increased surface microscale roughness since larger surface areas (especially when irregular) provide binding sites and protection. Increased smoothness of the surface should prevent bacterial colonization. A similar scenario is found with corrosion associated surface micro-cracks that are prone to infection. On the other hand, exceptionally smooth materials can increase the bacterial attachment via physical forces such as van der Waals interactions (double rows) and by providing a number of molecular contact points.

Figure 4

Potential mechanisms by which antibacterial substances kill bacteria; critical targets include bacterial cells genome, metabolic and respiration pathways, cell envelope synthesis and membrane disruptors (e.g., reactive oxygen species).

Figure 5

Two examples of antibacterial effect located on the surface of an implant. The first example demonstrates Vancomycin linkage to a carrier polymer; the second example shows tethered cationic antimicrobial peptides creating a contact killing surface utilizing recombinant human β-defensin-2 (rHUβD2).

Figure 6

Plasma-surface modification techniques creating a special type of antimicrobial surface involving silver (Ag) nanoparticles embedded into titanium (Ti); it is proposed that Ag and Ti represent a micro-galvanic pair with different potentials in the presence of electrolyte solution; the cathodic reaction will create a proton-depleted region between bacterial membrane and Ti substrate, which leads to disruption of the adenosine triphosphate synthesis and bacteria death.

Figure 7

Smart coatings continuously screen the local effective space using molecular receptors specific to a surrounding target’s signals. Stimulation of target-sensitive receptors triggers a cascade of events resulting in outflow of specific substance(s) that affect the target.