Tetracycline tethered to titanium inhibits colonization by Gram‐negative bacteria

Abstract

As peri-prosthetic infection is one of the most devastating complications associated with implant placement, we have reasoned that such infection can be largely subverted by development of antibacterial implants. Our previous work demonstrated that covalent coupling of vancomycin to titanium alloy prevented colonization by the gram-positive pathogens, Staphylococcus aureus and Staphylococcus epidermidis. Some orthopaedic devices, including permanent prosthesis anchors, and most dental implants are transcutaneous or transmucosal and can be prone to colonization by Gram-negative pathogens. We report here the successful covalent coupling of the broad-spectrum antibiotic, tetracycline (TET), to titanium surfaces (Ti-TET) to retard Gram-negative colonization. Synthetic progress was followed by changes in water contact angle, while the presence of TET was confirmed by immunofluorescence. Ti-TET actively prevented colonization in the presence of bathing Escherichia coli, both by fluorescence microscopy and direct counting. Finally, the Ti-TET surface supported osteoblastic cell adhesion and proliferation over a 72 hour period. Thus, this new surface offers a powerful means to protect transcutaneous implants from adhesion of Gram-negative pathogens, decreasing the need for replacement of this hardware.

Biofunctionalization of titanium with bacitracin immobilization shows potential for anti-bacteria, osteogenesis and reduction of macrophage inflammation

“…However, previous studies have demonstrated that the tethered antibiotics such as vancomycin could block osseointegration processes by down-regulating the molecules required for pre-osteoblast recruitment, proliferation, differentiation and maturation [11,12,24]. Thus, given that the antibiotic itself appears to impair the process of osseointegration, development of an antibiotic possessing both antibacterial properties and the ability to promote osteogenic differentiation would be an ideal candidate for the biofunctionalization of the Ti.…”

“…Various approaches had been employed in the fabrication of a biofunctional Ti surface, including changes to surface coating or morphology and the use of covalent or controlled-release antibacterial or bioactive agents on the Ti surface [10][11][12]. However, these strategies have thus far been based on a simple design for singlebiofunctionalization of Ti to either confer an antibacterial property or promote osteogenic differentiation.…”

Antimicrobial dental implant functionalization strategies —A systematic review

“…An interactive implant surface with pH-dependent or infection-dependent antibiotic release might avoid this shortcoming, but has not yet been introduced to dental implant materials research. Antibiotics are capable of reducing bacterial colonization with S. mutans 22,39) S. epidermidis 31) and S.aureus 38) , P. gingivalis, A. actinomycetemcomitans, P. intermedia, P. aeruginosa 40) and E. coli 21,23,36) on titanium surfaces. Chlorhexidine (CHX)-loaded titanium surfaces reduce colonization with streptococci and S. aureus in comparison to titanium control [24][25][26] .…”

“…The results showed enhanced alkaline phosphatase activity and calcium deposition by osteoblast cells 27) . Antibiotic-releasing surfaces were non-toxic to osteoblast cells and showed good cytocompatibility compared to uncoated titanium 21,31,36) . Load concentrations of 1.4 and 0.7% CHX resulted in harmful changes in eukaryotic cell morphology, including shrinkage, smaller and pyknotic cells, and loss of cytoplasmic processes, which suggests that there are cytotoxic effects.…”

Cell Guidance on Nanostructured Metal Based Surfaces

“…Various solutions have been recently proposed to improve antibacterial properties of titanium implants: embedment of Ag nanoparticles, ion implantation of Ag, Cu, Zn ions, silver doped hydroxyapatite coatings, covalent coupling of antibiotics such as tetracyclin and vancomycin, ZnO coatings, immobilization of anhydride‐functional silane, chitosan/cefepime nanofiber coatings, etc. Here we discuss two strategies: (1) release of biocide agent; (2) formation of stimuli responsive coating to “push” bacteria “off” the surface.…”