Prevention of orthopaedic bacterial related infections by incorporating a single positive charge with particular hydrophobicity molecule

Abstract

Titanium and titanium alloys are widely applied in orthopaedics and other medical devices because of their good biocompatibility and mechanical strength. Examples of their applications include internal and external fixations and total joint replacement. However, surfaces of titanium implants often allow the adhesion of bacteria, promote their anchor and eventually lead to biofilm formation. Subsequent results include implant associated infections and osteomyelitis. Effectiveness, durability and cytocompatibility of the implants are the main issues when deciding what implants are suitable for different clinical uses. Failure in providing a long lasting antibacterial property of the implant, insufficiency of targeting a broad spectrum of bacteria, increase in the chance of developing drug resistance bacteria and the involvement of the complicated fabricating techniques are still major problems. Implant associated infections can lead to devastating consequences such as prolonged hospitalization in terms of systemic antibiotic therapy, wound debridement, removal of implants or even death.

There are two common treatment methods for solving the problem of osteomyelitis: either preventing the initial bacterial attachment or inhibiting the infection by tackling the biofilm. Biofilm itself produces a hydrated polymeric matrix which can subsequently prevent attack from antibiotics. Therefore, the current investigation could focus more on modifying the biomaterial surface in order to increase the initial bacterial adhesion resistance, including modifications to its surface topography and chemistry.

When modifying biomaterial surfaces, the important criteria for an effective and practical implant are its manufacturing cost and the ease of fabrication. It should be permanent and effective against a broad spectrum of bacteria in order to prevent the incidence of osteomyelitis, and widespread applicability is also another essential consideration.

In this project, a covalently bonded single positively charged small molecule with a certain degree of hydrophobicity, APTES, was coated onto the Ti alloy surface in order to prevent implant associated infection. The potential advantages of this small molecule were significant. It possessed a broad-spectrum antibacterial activity with over 90% reduction upon initial attachment against both gram positive and negative bacteria, including Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The coating can inhibit 75.5% of bacterial growth against S.aureus while maintaining cytocompatibility which was evaluated by MTT and LDH cytotoxicity assays. The mechanism of the antibacterial action of the APTES coated surface was also investigated by comparing it with other kinds of coating surfaces. The results indicated the functional group NH2 has one single positive charge with optimum hydrophobicity, which was essential in order to perform as an excellent antibacterial property.

The advantages of employing this small molecule were that it only involves simple procedures in fabrication, which can significantly reduce the manufacturing cost and time. This molecule is coated by a covalent bond and is not based on a releasing mechanism, and therefore its antibacterial property can be long lasting. Lastly, it was foreseeable that this cheap but effective implant coating method with good cytocompatibility could be widely applied in all kinds of medical devices for osteomyelitis prevention and could also eventually benefit patients suffering from orthopaedic conditions.