Characterization of high-fracture toughness K-fluorrichterite-fluorapatite glass ceramics

Stoichiometric K-fluorrichterite (Glass A) and the same composition with 2 mol% P2O5 added (Glass B) were prepared and then heat-treated isothermally from 550°1000°C with 50°C intervals. Samples were characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). The biaxial flexural strength and indentation fracture toughness of heat-treated glass specimens were also determined for both materials. XRD traces and TEM images showed similar phase evolution and fine microstructures for both systems at ≤950°C, with mica and diopside reacting with residual glass to form K-fluorrichterite as the temperature was increased from 650°C. However, in Glass B, fluorapatite was also present at >800°C. In contrast, coarser microstructures were observed at 1000°C, with larger K-fluorrichterite (20 μm) and enstatite (10 μm) crystals in Glasses A and B, respectively. The highest fracture toughness (2.69 ± 0.01 MPa·m(1/2)) and biaxial strength (242.6 ± 3.6 MPa) were recorded for Glass B heat-treated at 1000°C. This was attributed to the presence of enstatite coupled with an interlocked lath-like crystalline microstructure

The Effect of RANKL/OPG Balance on Reducing Implant Complications

Despite the phenomenal success of implants particularly in the realms of dentistry and orthopaedics, there are still challenges to overcome. The failure of implants resulting from infection, prosthetic loosening, and non-union continue to be the most notorious examples. The cascade of fracture healing and bone repair, especially with the presence of an implant, is complex because it involves a multifaceted immune response alongside the intricate process of bone formation and remodelling. Bone loss is a serious clinical problem that is frequently accompanied by chronic inflammation, illustrating that there is a convoluted relationship between inflammation and bone erosion. The effects of pro-inflammatory factors play a significant role in initiating and maintaining osteoclastogenesis that results in bone resorption by osteoclasts. This is because there is a disruption of the relative ratio between Receptor Activator of Nuclear Factor κB-Ligand (RANKL) and osteoprotegerin (OPG), which is central to modulating bone repair and remodelling. This review aims to provide a background to the bone remodelling process, the bone repair cascade post-implantation, and the associated complications. Furthermore, current clinical solutions that can influence bone formation via either internal or extrinsic mechanisms will be described. These efficacious treatments for osteolysis via targeting the RANKL/OPG ratio may be crucial to reducing the incidence of related implant failures in the future

Rapid Mix Preparation of Bioinspired Nanoscale Hydroxyapatite for Biomedical Applications

Hydroxyapatite (HA) has been widely used as a medical ceramic due to its good biocompatibility and osteoconductivity. Recently there has been interest regarding the use of bioinspired nanoscale hydroxyapatite (nHA). However, biological apatite is known to be calcium-deficient and carbonate-substituted with a nanoscale platelet-like morphology. Bioinspired nHA has the potential to stimulate optimal bone tissue regeneration due to its similarity to bone and tooth enamel mineral. Many of the methods currently used to fabricate nHA both in the laboratory and commercially, involve lengthy processes and complex equipment. Therefore, the aim of this study was to develop a rapid and reliable method to prepare high quality bioinspired nHA. The rapid mixing method developed was based upon an acid-base reaction involving calcium hydroxide and phosphoric acid. Briefly, a phosphoric acid solution was poured into a calcium hydroxide solution followed by stirring, washing and drying stages. Part of the batch was sintered at 1,000 °C for 2 h in order to investigate the products' high temperature stability. X-ray diffraction analysis showed the successful formation of HA, which showed thermal decomposition to β-tricalcium phosphate after high temperature processing, which is typical for calcium-deficient HA. Fourier transform infrared spectroscopy showed the presence of carbonate groups in the precipitated product. The nHA particles had a low aspect ratio with approximate dimensions of 50 x 30 nm, close to the dimensions of biological apatite. The material was also calcium deficient with a Ca:P molar ratio of 1.63, which like biological apatite is lower than the stoichiometric HA ratio of 1.67. This new method is therefore a reliable and far more convenient process for the manufacture of bioinspired nHA, overcoming the need for lengthy titrations and complex equipment. The resulting bioinspired HA product is suitable for use in a wide variety of medical and consumer health applications

An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering

Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function

Resin-based composite materials: elution and pollution

Pollution arises from all human activity and the provision of oral healthcare using resin-based composite restorative materials (RBCs) should be considered. This paper aims to provide a comprehensive review of the potential pollutant risk to the environment from the chemical compounds found in resin-based restorative materials, by including: 1) the principal pollutant compounds present in the resin matrix; 2) the degradation process of RBCs and its consequences; 3) the methods used for the detection and quantification of monomer elution and RBC microparticles; and 4) a review of the release mechanisms of eluates and RBC microparticles into the environment. RBCs are pollutants by virtue of the compounds created during the degradation processes. These are in the form of the constituent eluted monomers and microparticles. Their impact on the environment and biodiversity is unknown. These materials are currently one of the main direct-placement restorative materials and their success is unquestionable when used and maintained correctly. Mitigation strategies for reducing the impact of pollution on the environment should be considered and implemented by all stakeholders and processes in the supply chain, from manufacturing, clinical use and waste management

Medium-chain fatty acids released from polymeric electrospun patches inhibit Candida albicans growth and reduce the biofilm viability

Oral candidiasis is a very common oral condition among susceptible individuals, with the main causative organism being the fungus Candida albicans. Current drug delivery systems to the oral mucosa are often ineffective because of short drug/tissue contact times as well as increased prevalence of drug-resistant Candida strains. We evaluated the potency of saturated fatty acids as antifungal agents and investigated their delivery by novel electrospun mucoadhesive oral patches using agar disk diffusion and biofilm assays. Octanoic (C8) and nonanoic (C9) acids were the most effective at inhibiting C. albicans growth on disk diffusion assays, both in solution or when released from polycaprolactone (PCL) or polyvinylpyrrolidone/RS100 (PVP/RS100) electrospun patches. In contrast, dodecanoic acid (C12) displayed the most potent antifungal activity against pre-existing C. albicans biofilms in solution or when released by PCL or PVP/RS100 patches. Both free and patch-released saturated fatty acids displayed a significant toxicity to wild-type and azole-resistant strains of C. albicans. These data not only provide evidence that certain saturated fatty acids have the potential to be used as antifungal agents but also demonstrate that this therapy could be delivered directly to Candida-infected sites using electrospun mucoadhesive patches, demonstrating a potential new therapeutic approach to treat oral thrush

Mucoadhesive electrospun fibre-based technologies for oral medicine

Oral disease greatly affects quality of life, as the mouth is required for a wide range of activities including speech, food and liquid consumption. Treatment of oral disease is greatly limited by the dose forms that are currently available, which suffer from short contact times, poor site specificity, and sensitivity to mechanical stimulation. Mucoadhesive devices prepared using electrospinning offer the potential to address these challenges by allowing unidirectional site-specific drug delivery through intimate contact with the mucosa and with high surface areas to facilitate drug release. This review will discuss the range of electrospun mucoadhesive devices that have recently been reported to address oral inflammatory diseases, pain relief, and infections, as well as new treatments that are likely to be enabled by this technology in the future

Incorporation of lysozyme into a mucoadhesive electrospun patch for rapid protein delivery to the oral mucosa

The delivery of biopharmaceuticals to the oral mucosa offers a range of potential applications including antimicrobial peptides to treat resistant infections, growth factors for tissue regeneration, or as an alternative to injections for systemic delivery. Existing formulations targeting this site are typically non-specific and provide little control over dose. To address this, an electrospun dual-layer mucoadhesive patch was investigated for protein delivery to the oral mucosa. Lysozyme was used as a model antimicrobial protein and incorporated into poly(vinylpyrrolidone)/Eudragit RS100 polymer nanofibers using electrospinning from an ethanol/water mixture. The resulting fibrous membranes released the protein at a clinically desirable rate, reaching 90 ± 13% cumulative release after 2 h. Dual fluorescent fibre labelling and confocal microscopy demonstrated the homogeneity of lysozyme and polymer distribution. High encapsulation efficiency and preservation of enzyme activity were achieved (93.4 ± 7.0% and 96.1 ± 3.3% respectively). The released lysozyme inhibited the growth of the oral bacterium Streptococcus ratti, providing further evidence of retention of biological activity and illustrating a potential application for treating and preventing oral infections. An additional protective poly(caprolactone) backing layer was introduced to promote unidirectional delivery, without loss of enzyme activity, and the resulting dual-layer patches displayed long residence times using an in vitro test, showing that the adhesive properties were maintained. This study demonstrates that the drug delivery system has great potential for the delivery of therapeutic proteins to the oral mucosa

Osteosarcoma growth on trabecular bone mimicking structures manufactured via laser direct write

This paper describes the direct laser write of a photocurable acrylate-based PolyHIPE (High Internal Phase Emulsion) to produce scaffolds with both macro- and microporosity, and the use of these scaffolds in osteosarco-ma-based 3D cell culture. The macroporosity was introduced via the application of stereolithography to produce a clas-sical woodpile structure with struts having an approximate diameter of 200 ?m and pores were typically around 500 ?m in diameter. The PolyHIPE retained its microporosity after stereolithographic manufacture, with a range of pore sizes typically between 10 and 60 ?m (with most pores between 20 and 30 ?m). The resulting scaffolds were suitable substrates for further modification using acrylic acid plasma polymerisation. This scaffold was used as a structural mimic of the trabecular bone and in vitro determination of biocompatibility using cultured bone cells (MG63) demon-strated that cells were able to colonise all materials tested, with evidence that acrylic acid plasma polymerisation im-proved biocompatibility in the long term. The osteosarcoma cell culture on the 3D printed scaffold exhibits different growth behaviour than observed on tissue culture plastic or a flat disk of the porous material; tumour spheroids are ob-served on parts of the scaffolds. The growth of these spheroids indicates that the osteosarcoma behave more akin to in vivo in this 3D mimic of trabecular bone. It was concluded that PolyHIPEs represent versatile biomaterial systems with considerable potential for the manufacture of complex devices or scaffolds for regenerative medicine. In particular, the possibility to readily mimic the hierarchical structure of native tissue enables opportunities to build in vitro models closely resembling tumour tissue

Osteosarcoma growth on trabecular bone mimicking structures manufactured via laser direct write

This paper describes the direct laser write of a photocurable acrylate-based PolyHIPE (High Internal Phase Emulsion) to produce scaffolds with both macro- and microporosity, and the use of these scaffolds in osteosarco-ma-based 3D cell culture. The macroporosity was introduced via the application of stereolithography to produce a clas-sical woodpile structure with struts having an approximate diameter of 200 ?m and pores were typically around 500 ?m in diameter. The PolyHIPE retained its microporosity after stereolithographic manufacture, with a range of pore sizes typically between 10 and 60 ?m (with most pores between 20 and 30 ?m). The resulting scaffolds were suitable substrates for further modification using acrylic acid plasma polymerisation. This scaffold was used as a structural mimic of the trabecular bone and in vitro determination of biocompatibility using cultured bone cells (MG63) demon-strated that cells were able to colonise all materials tested, with evidence that acrylic acid plasma polymerisation im-proved biocompatibility in the long term. The osteosarcoma cell culture on the 3D printed scaffold exhibits different growth behaviour than observed on tissue culture plastic or a flat disk of the porous material; tumour spheroids are ob-served on parts of the scaffolds. The growth of these spheroids indicates that the osteosarcoma behave more akin to in vivo in this 3D mimic of trabecular bone. It was concluded that PolyHIPEs represent versatile biomaterial systems with considerable potential for the manufacture of complex devices or scaffolds for regenerative medicine. In particular, the possibility to readily mimic the hierarchical structure of native tissue enables opportunities to build in vitro models closely resembling tumour tissue