Antibacterial surface modification of titanium implants in orthopaedics

The use of biomaterials in orthopaedics for joint replacement, fracture healing and bone regeneration is a rapidly expanding field. Infection of these biomaterials is a major healthcare burden, leading to significant morbidity and mortality. Furthermore, the cost to healthcare systems is increasing dramatically. With advances in implant design and production, research has predominately focussed on osseointegration; however, modification of implant material, surface topography and chemistry can also provide antibacterial activity. With the increasing burden of infection, it is vitally important that we consider the bacterial interaction with the biomaterial and the host when designing and manufacturing future implants. During this review, we will elucidate the interaction between patient, biomaterial surface and bacteria. We aim to review current and developing surface modifications with a view towards antibacterial orthopaedic implants for clinical applications

Embedded disposable functionalized electrochemical biosensor with a 3D-printed flow cell for detection of hepatic oval cells (HOCs)

Hepatic oval cells (HOCs) are considered the progeny of the intrahepatic stem cells that are found in a small population in the liver after hepatocyte proliferation is inhibited. Due to their small number, isolation and capture of these cells constitute a challenging task for immunosensor technology. This work describes the development of a 3D-printed continuous flow system and exploits disposable screen-printed electrodes for the rapid detection of HOCs that over-express the OV6 marker on their membrane. Multiwall carbon nanotube (MWCNT) electrodes have a chitosan film that serves as a scaffold for the immobilization of oval cell marker antibodies (anti-OV6-Ab), which enhance the sensitivity of the biomarker and makes the designed sensor specific for oval cells. The developed sensor can be easily embedded into the 3D-printed flow cell to allow cells to be exposed continuously to the functionalized surface. The continuous flow is intended to increase capture of most of the target cells in the specimen. Contact angle measurements were performed to characterize the nature and quality of the modified sensor surface, and electrochemical measurements (cyclic voltammetry (CV) and square wave voltammetry (SWV)) were performed to confirm the efficiency and selectivity of the fabricated sensor to detect HOCs. The proposed method is valuable for capturing rare cells and could provide an effective tool for cancer diagnosis and detection

Role of polymers in microfluidic devices

Polymers are sustainable and renewable materials that are in high demand due to their excellent properties. Natural and synthetic polymers with high flexibility, good biocompatibility, good degradation rate, and stiffness are widely used for various applications, such as tissue engineering, drug delivery, and microfluidic chip fabrication. Indeed, recent advances in microfluidic technology allow the fabrication of polymeric matrix to construct microfluidic scaffolds for tissue engineering and to set up a well-controlled microenvironment for manipulating fluids and particles. In this review, polymers as materials for the fabrication of microfluidic chips have been highlighted. Successful models exploiting polymers in microfluidic devices to generate uniform particles as drug vehicles or artificial cells have been also discussed. Additionally, using polymers as bioink for 3D printing or as a matrix to functionalize the sensing surface in microfluidic devices has also been mentioned. The rapid progress made in the combination of polymers and microfluidics presents a low-cost, reproducible, and scalable approach for a promising future in the manufacturing of biomimetic scaffolds for tissue engineering

Impact of surface topography and coating on osteogenesis and bacterial attachment on titanium implants

Titanium (Ti) plays a predominant role as the material of choice in orthopaedic and dental implants. Despite the majority of Ti implants having long-term success, premature failure due to unsuccessful osseointegration leading to aseptic loosening is still too common. Recently, surface topography modification and biological/non-biological coatings have been integrated into orthopaedic/dental implants in order to mimic the surrounding biological environment as well as reduce the inflammation/infection that may occur. In this review, we summarize the impact of various Ti coatings on cell behaviour both in vivo and in vitro. First, we focus on the Ti surface properties and their effects on osteogenesis and then on bacterial adhesion and viability. We conclude from the current literature that surface modification of Ti implants can be generated that offer both osteoinductive and antimicrobial properties

Enhanced and stem-cell-compatible effects of nature-inspired antimicrobial nanotopography and antimicrobial peptides to combat implant-associated infection

Nature-inspired antimicrobial surfaces and antimicrobial peptides (AMPs) have emerged as promising strategies to combat implant-associated infections. In this study, a bioinspired antimicrobial peptide was functionalized onto a nanospike (NS) surface by physical adsorption with the aim that its gradual release into the local environment would enhance inhibition of bacterial growth. Peptide adsorbed on a control flat surface exhibited different release kinetics compared to the nanotopography, but both surfaces showed excellent antibacterial properties. Functionalization with peptide at micromolar concentrations inhibited Escherichia coli growth on the flat surface, Staphylococcus aureus growth on the NS surface, and Staphylococcus epidermidis growth on both the flat and NS surfaces. Based on these data, we propose an enhanced antibacterial mechanism whereby AMPs can render bacterial cell membranes more susceptible to nanospikes, and the membrane deformation induced by nanospikes can increase the surface area for AMPs membrane insertion. Combined, these effects enhance bactericidal activity. Since functionalized nanostructures are highly biocompatible with stem cells, they make promising candidates for next generation antibacterial implant surfaces

Materials-driven fibronectin assembly on nanoscale topography enhances mesenchymal stem cell adhesion, protecting cells from bacterial virulence factors and preventing biofilm formation

Dataset files were updated on 2021-12-09 to include additional files

Materials-driven fibronectin assembly on nanoscale topography enhances mesenchymal stem cell adhesion, protecting cells from bacterial virulence factors and preventing biofilm formation

Post-operative infection is a major complication in patients recovering from orthopaedic surgery. As such, there is a clinical need to develop biomaterials for use in regenerative surgery that can promote mesenchymal stem cell (MSC) osteospecific differentiation and that can prevent infection caused by biofilm-forming pathogens. Nanotopographical approaches to pathogen control are being identified, including in orthopaedic materials such as titanium and its alloys. These topographies use high aspect ratio nanospikes or nanowires to prevent bacterial adhesion but these features also significantly reduce MSC adhesion and activity. Here, we use a poly (ethyl acrylate) (PEA) polymer coating on titanium nanowires to spontaneously organise fibronectin (FN) and to deliver bone morphogenetic protein 2 (BMP2) to enhance MSC adhesion and osteospecific signalling. Using a novel MSC-Pseudomonas aeruginosa co-culture, we show that the coated nanotopographies protect MSCs from cytotoxic quorum sensing and signalling molecules, enhance MSC adhesion and osteoblast differentiation and reduce biofilm formation. We conclude that the PEA polymer-coated nanotopography can both support MSCs and prevent pathogens from adhering to a biomaterial surface, thus protecting from biofilm formation and bacterial infection, and supporting osteogenic repair

Materials-driven Fibronectin Assembly on Nanoscale Topography Enhances Mesenchymal Stem Cell Adhesion, Protecting Cells from Bacterial Virulence Factors and Preventing Biofilm Formation

Post-operative infection is a major complication in patients recovering from orthopaedic surgery. As such, there is a clinical need to develop biomaterials for use in regenerative surgery that can promote mesenchymal stem cell (MSC) osteospecific differentiation and that can prevent infection caused by biofilm-forming pathogens. Nanotopographical approaches to pathogen control are being identified, including in orthopaedic materials such as titanium and its alloys. These topographies use high aspect ratio nanospikes or nanowires to prevent bacterial adhesion but these features also significantly reduce MSC adhesion and activity. Here, we use a poly (ethyl acrylate) (PEA) polymer coating on titanium nanowires to spontaneously organise fibronectin (FN) and to deliver bone morphogenetic protein 2 (BMP2) to enhance MSC adhesion and osteospecific signalling. Using a novel MSC–Pseudomonas aeruginosa co-culture, we show that the coated nanotopographies protect MSCs from cytotoxic quorum sensing and signalling molecules, enhance MSC adhesion and osteoblast differentiation and reduce biofilm formation. We conclude that the PEA polymer-coated nanotopography can both support MSCs and prevent pathogens from adhering to a biomaterial surface, thus protecting from biofilm formation and bacterial infection, and supporting osteogenic repair