A novel chlorhexidine-hexametaphosphate coating for titanium with antibiofilm efficacy and stem cell cytocompatibility

Abstract Dental implants are an increasingly popular way to replace missing teeth. Whilst implant survival rates are high, a small number fail soon after placement, with various factors, including bacterial contamination, capable of disrupting osseointegration. This work describes the development of chlorhexidine-hexametaphosphate coatings for titanium that hydrolyse to release the antiseptic agent chlorhexidine. The aim was to develop a coating for titanium that released sufficient chlorhexidine to prevent biofilm formation, whilst simultaneously maintaining cytocompatibility with cells involved in osseointegration. The coatings were characterised with respect to physical properties, after which antibiofilm efficacy was investigated using a multispecies biofilm model, and cytocompatibility determined using human mesenchymal stem cells. The coatings exhibited similar physicochemical properties to some implant surfaces in clinical use, and significantly reduced formation of multispecies biofilm biomass up to 72 h. One coating had superior cytocompatibility, with mesenchymal stem cells able to perform normal functions and commence osteoblastic differentiation, although at a slower rate than those grown on uncoated titanium. With further refinement, these coatings may have application in the prevention of bacterial contamination of dental implants at the time of surgery. This could aid a reduction in rates of early implant failure

O-mannosylation in Candida albicans enables development of interkingdom biofilm communities

Peer reviewedPublisher PD

Understanding the Matrix:The Role of Extracellular DNA in Oral Biofilms

Dental plaque is the key etiological agent in caries formation and the development of the prevalent chronic oral inflammatory disease, periodontitis. The dental plaque biofilm comprises a diverse range of microbial species encased within a rich extracellular matrix, of which extracellular DNA (eDNA) has been identified as an important component. The molecular mechanisms of eDNA release and the structure of eDNA have yet to be fully characterized. Nonetheless, key functions that have been proposed for eDNA include maintaining biofilm structural integrity, initiating adhesion to dental surfaces, acting as a nutrient source, and facilitating horizontal gene transfer. Thus, eDNA is a potential therapeutic target for the management of oral disease–associated biofilm. This review aims to summarize advances in the understanding of the mechanisms of eDNA release from oral microorganisms and in the methods of eDNA detection and quantification within oral biofilms

Osteogenic and bactericidal surfaces from hydrothermal titania nanowires on titanium substrates

Nanotopographical cues on Ti have been shown to elicit different cell responses such as cell differentiation and selective growth. Bone remodelling is a constant process requiring specific cues for optimal bone growth and implant fixation. Moreover, biofilm formation and the resulting infection on surgical implants is a major issue. Our aim is to identify nanopatterns on Ti surfaces that would be optimal for both bone remodelling and for reducing risk of bacterial infection. Primary human osteoblast/osteoclast co-cultures were seeded onto Ti substrates with TiO2 nanowires grown under alkaline conditions at 240 °C for different times (2, 2.5 or 3 h). Cell growth and behaviour was assessed by scanning electron microscopy (SEM), immunofluorescence microscopy, histochemistry and quantitative RT-PCR methods. Bacterial colonisation of the nanowire surfaces was also assessed by confocal microscopy and SEM. From the three surfaces tested the 2 h nanowire surface supported osteoblast and to a lesser extent osteoclast growth and differentiation. At the same time bacterial viability was reduced. Hence the 2 h surface provided optimal bone remodeling in vitro conditions while reducing infection risk, making it a favourable candidate for future implant surfaces

The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism

Adherence of bacteria to biotic or abiotic surfaces is a prerequisite for host colonization and represents an important step in microbial pathogenicity. This attachment is facilitated by bacterial adhesins at the cell surface. Because of their size and often elaborate multidomain architectures, these polypeptides represent challenging targets for detailed structural and functional characterization. The multifunctional fibrillar adhesin CshA, which mediates binding to both host molecules and other microorganisms, is an important determinant of colonization by Streptococcus gordonii, an oral commensal and opportunistic pathogen of animals and humans. CshA binds the high-molecular-weight glycoprotein fibronectin (Fn) via an N-terminal non-repetitive region, and this protein-protein interaction has been proposed to promote S. gordonii colonization at multiple sites within the host. However, the molecular details of how these two proteins interact have yet to be established. Here we present a structural description of the Fn binding N-terminal region of CshA, derived from a combination of X-ray crystallography, small angle X-ray scattering, and complementary biophysical methods. In vitro binding studies support a previously unreported two-state “catch-clamp” mechanism of Fn binding by CshA, in which the disordered N-terminal domain of CshA acts to “catch” Fn, via formation of a rapidly assembled but also readily dissociable pre-complex, enabling its neighboring ligand binding domain to tightly clamp the two polypeptides together. This study presents a new paradigm for target binding by a bacterial adhesin, the identification of which will inform future efforts toward the development of anti-adhesive agents that target S. gordonii and related streptococci