Adhesion of bioactive glass-based adhesive to bone.

Understanding the failure modes and the fracture resistance is critical in evaluating the performance of an adhesive for sternal fixation. In this paper, a fracture mechanics testing methodology was used to assess the adhesion of a bioactive glass-based adhesive to bovine bone in terms of a measured mode I critical strain energy release rate (GIC). Reinforced double cantilever beam (DCB) samples were observed to produce repeatable values of GIC. The measured GIC was found to increase significantly from 5.41 to 12.60 J/m2 with an increase in adhesive thickness from 390 to 990 µm because of the constraint from the two adherends regulating the plastic zone size ahead of the crack. The specimens failed cohesively in all cases demonstrating that there was good adhesion to bone, a condition necessary to restrict micromotion and thus provide rigid sternal fixation when used along with sternal wires. It was also found that when the bone was flooded with liquid during adhesive application a much lower GIC of between 0.69 and 1.15 J/m2 was measured. Overall, the results demonstrate that the fracture mechanics approach can be used to provide a quantitative measure of the adhesion of the bioactive glass-based adhesive to the bone and that the adhesive should only be applied to clean bone in a dry environment.

Comparative Evaluation of Two Glass Polyalkenoate Cements: An In Vivo Pilot Study Using a Sheep Model.

Poly(methyl methacrylate) (PMMA) is used to manage bone loss in revision total knee arthroplasty (rTKA). However, the application of PMMA has been associated with complications such as volumetric shrinkage, necrosis, wear debris, and loosening. Glass polyalkenoate cements (GPCs) have potential bone cementation applications. Unlike PMMA, GPC does not undergo volumetric shrinkage, adheres chemically to bone, and does not undergo an exothermic setting reaction. In this study, two different compositions of GPCs (GPCA and GPCB), based on the patented glass system SiO2-CaO-SrO-P2O5-Ta2O5, were investigated. Working and setting times, pH, ion release, compressive strength, and cytotoxicity of each composition were assessed, and based on the results of these tests, three sets of samples from GPCA were implanted into the distal femur and proximal tibia of three sheep (alongside PMMA as control). Clinical CT scans and micro-CT images obtained at 0, 6, and 12 weeks revealed the varied radiological responses of sheep bone to GPCA. One GPCA sample (implanted in the sheep for 12 weeks) was characterized with no bone resorption. Furthermore, a continuous bone-cement interface was observed in the CT images of this sample. The other implanted GPCA showed a thin radiolucent border at six weeks, indicating some bone resorption occurred. The third sample showed extensive bone resorption at both six and 12 weeks. Possible speculative factors that might be involved in the varied response can be: excessive Zn2+ ion release, low pH, mixing variability, and difficulty in inserting the samples into different parts of the sheep bone.

In vivo analysis of a proprietary glass-based adhesive for sternal fixation and stabilization using rabbit and sheep models.

Wire cerclage remains the standard method of care for sternal fixation, following median sternotomy, despite being beset with complications. An emerging treatment option has been to augment the wires with an adhesive. A patented ionomeric glass (mole fraction: SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04) has been used to formulate GPC+, a glass polyalkenoate cement (GPC), by mixing it with poly(acrylic) acid (PAA) and de-ionized water. In a human cadaver study, this material, when applied with wire cerclage, was able to significantly reduce sternal instability. However, the material has yet to be tested in pertinent animal models. Here, after a series of physical and mechanical tests to confirm suitability of the experimental material for implantation, three samples of GPC+ were implanted in either the tibia or femur of three different rabbits, alongside sham defects, for two different time modalities. A further seven samples of GPC+ and one poly(methyl methacrylate) control (PMMA) were implanted in either the tibia or femur of two different sheep. The sheep containing the PMMA was sacrificed at 8 weeks and the other at 16 weeks, to evaluate time dependent biological response. Upon sacrifice, microCT images were acquired and histology slides prepared for analysis. All three GPC+ samples implanted in the rabbit model, for the two time modalities, were characterized by minimal bone resorption along with a mild inflammatory response. Five of the seven GPC+ materials implanted in the sheep model (all three implanted for 8 weeks and two of those implanted for 16 weeks) were associated with mild to moderate immune response, comparable to that observed with PMMA, as well as mild bone resorption. The remaining two GPC + materials (implanted in the sheep model for 16 weeks) exhibited no bone resorption or inflammatory response and appeared to stimulate increased bone density at the implant site. These results suggest that GPC + can be a viable bone adhesive for use in hard tissue applications such as sternal fixation and stabilization. Experiments performed to synthesize & test Sr-doped glass adhesive for sternal fixation. (1) Sr-doped ionomeric glass fired, ground down and mixed with aqueous polyacrylic acid to produce the adhesive. (2) Adhesive characterized and tested by a suite of laboratory-based tests to ensure suitability for implantation. (3) Adhesive implanted into a rabbit model (distal femur, 12 weeks post implantation) where micro-CT images confirmed an excellent bone/cement interface, no evidence of bone resorption and some bone remodelling. (4) Adhesive subsequently implanted into a sheep model; at 16-weeks, a continuous bone-adhesive interface is seen suggesting no bone resorption. There was an increase in the peri-implant radiodensity, suggesting enhanced mineral content of the bone surrounding the GPC+ implant.

Bone cement as a local chemotherapeutic drug delivery carrier in orthopedic oncology: A review.

Metastatic bone lesions are common among patients with advanced cancers. While chemotherapy and radiotherapy may be prescribed immediately after diagnosis, the majority of severe metastatic bone lesions are treated by reconstructive surgery, which, in some cases, is followed by postoperative radiotherapy or chemotherapy. However, despite recent advancements in orthopedic surgery, patients undergoing reconstruction still have the risk of developing severe complications such as tumor recurrence and reconstruction failure. This has led to the introduction and evaluation of poly (methyl methacrylate) and inorganic bone cements as local carriers for chemotherapeutic drugs (usually, antineoplastic drugs (ANPDs)). The present work is a critical review of the literature on the potential use of these cements in orthopedic oncology. While several studies have demonstrated the benefits of providing high local drug concentrations while minimizing systemic side effects, only six studies have been conducted to assess the local toxic effect of these drug-loaded cements and they all reported negative effects on healthy bone structure. These findings do not close the door on chemotherapeutic bone cements; rather, they should assist in materials selection when designing future materials for the treatment of metastatic bone disease.

In vitro evaluation of novel titania-containing borate bioactive glass scaffolds.

Titanium-containing borate bioactive glass scaffolds (0, 5, 15, and 20 mol %, identified as BRT0, BRT1, BRT3, and BRT4) with a microstructure similar to that of human trabecular bone were prepared and evaluated in vitro for potential bone loss applications in revision total knee arthroplasty (rTKA). Methyl thiazolyl tetrazolium (MTT) cell viability assays of scaffold ion release extracts revealed that BRT0 scaffolds (0 mol % titanium) inhibited cell proliferation and activity at day 14. At day 30, all scaffold extracts decreased cell proliferation and activity significantly. However, live/dead cell assay results demonstrated that degradation products from all the scaffolds had no inhibitory effect on cell viability. Significant bactericidal efficacies of BRT3 extracts against Escherishia coli (Gram-negative) and BRT1 extracts against Staphylococcus aureus and Staphylococcus epidermidis (both Gram-positive bacteria) were demonstrated. Finally, evaluation of the cell/bioactive glass surface interactions showed well-spread cells on the surface of the BRT3 glass discs and BRT1 and BRT3 scaffolds, when compared to BRT0 and BRT4 scaffolds. The results indicate that by changing the Ti4+ :B3+ ratio, the ion release and consequently cell proliferation could be improved. in vitro results in this study demonstrate that BRT3 scaffolds could be a promising candidate for addressing bone loss in rTKAs; however, in vivo studies would be required to evaluate the effect of a dynamic environment on the cell and tissue response to the fabricated scaffolds.

Tantalum-containing mesoporous bioactive glass powder for hemostasis.

This study evaluates the hemostatic properties of tantalum-containing mesoporous bioactive glasses (Ta-MBGs) through a suite of in-vitro methods: hemolysis percentage, zeta potential, blood coagulation assays (Activated Partial Thromboplastin Time - APTT and Prothrombin Time - PT) and cytotoxicity tests. Five compositions of Ta-MBG, with x mol% Ta2O5 added to the glass series (80-x)SiO2-15CaO-5P2O5-xTa2O5 where x=0 (0Ta), x=0.5 (0.5Ta), x=1 (1Ta), x=5 (5Ta), and x=10 (10Ta) mol%, were synthesised. The hemostatic potential of all the Ta-MBGs was confirmed by their negative zeta potential (-23 to -31 mV), which enhances the intrinsic pathway of blood coagulation. The hemolysis percentages of all Ta-MBGs except 10Ta showed statistically significant reductions compared to the same experiments carried out both in the absence of a sample ('no treatment' group) and in the presence of 10Ta. These observations validate the consideration of Ta-MBGs as hemostatic agents as they do not cause significant lysis of red blood cells. Cytotoxicity analysis revealed that Ta-MBGs had no effect on bovine fibroblast viability. Furthermore, a reduction in both APTT (a test to evaluate the intrinsic pathway of coagulation) and PT (a test to evaluate the extrinsic pathway) signified enhancement of hemostasis: 5Ta caused a significant reduction in APTT compared to 'no treatment', 1Ta and 10Ta and a significant reduction in PT compared to 0Ta. Therefore, we conclude that 5mol% of Ta optimised the hemostatic properties of these mesoporous bioactive glasses.

Calcium sulfate-containing glass polyalkenoate cement for revision total knee arthroplasty fixation.

Poly(methyl methacrylate) (PMMA) bone cement is used as a minor void filler in revision total knee arthroplasty (rTKA). The application of PMMA is indicated only for peripheral bone defects with less than 5 mm depth and that cover less than 50% of the bone surface. Treating bone defects with PMMA results in complications as a result of volumetric shrinkage, bone necrosis, and aseptic loosening. These concerns have driven the development of alternative bone cements. We report here on novel modified glass polyalkenoate cements (mGPCs) containing 1, 5 and 15 wt% calcium sulfate (CaSO4 ) and how the modified cements' properties compare to those of PMMA used in rTKA. CaSO4 is incorporated into the mGPC to improve both osteoconductivity and bioresorbability. The results confirm that the incorporation of CaSO4 into mGPCs decreases the setting time and increases release of therapeutic ions such as Ca2+ and Zn2+ over 30 days of maturation in deionized (DI) water. Moreover, the compressive strength for 5 and 15 wt% CaSO4 addition increased to over 30 MPa after 30 day maturation. Although the overall initial compressive strength of the mGPC (~ 30 MPa) is less than PMMA (~ 95 MPa), the compressive strength of mGPC is closer to that of cancellous bone (~ 1.2-7.8 MPa). CaSO4 addition did not affect biaxial flexural strength. Fourier transform infrared analysis indicated no cross-linking between CaSO4 and the GPC after 30 days. in vivo tests are required to determine the effects the modified GPCs as alternative on PMMA in rTKA.

The Role of Poly(Methyl Methacrylate) in Management of Bone Loss and Infection in Revision Total Knee Arthroplasty: A Review.

Poly(methyl methacrylate) (PMMA) is widely used in joint arthroplasty to secure an implant to the host bone. Complications including fracture, bone loss and infection might cause failure of total knee arthroplasty (TKA), resulting in the need for revision total knee arthroplasty (rTKA). The goals of this paper are: (1) to identify the most common complications, outside of sepsis, arising from the application of PMMA following rTKA, (2) to discuss the current applications and drawbacks of employing PMMA in managing bone loss, (3) to review the role of PMMA in addressing bone infection following complications in rTKA. Papers published between 1970 to 2018 have been considered through searching in Springer, Google Scholar, IEEE Xplore, Engineering village, PubMed and weblinks. This review considers the use of PMMA as both a bone void filler and as a spacer material in two-stage revision. To manage bone loss, PMMA is widely used to fill peripheral bone defects whose depth is less than 5 mm and covers less than 50% of the bone surface. Treatment of bone infections with PMMA is mainly for two-stage rTKA where antibiotic-loaded PMMA is inserted as a spacer. This review also shows that using antibiotic-loaded PMMA might cause complications such as toxicity to surrounding tissue, incomplete antibiotic agent release from the PMMA, roughness and bacterial colonization on the surface of PMMA. Although PMMA is the only commercial bone cement used in rTKA, there are concerns associated with using PMMA following rTKA. More research and clinical studies are needed to address these complications.

Effect of TiO2 doping on degradation rate, microstructure and strength of borate bioactive glass scaffolds.

A titanium-containing borate glass series based on the system (52-X) B2O3-12CaO-6P2O5-14Na2O-16ZnO-XTiO2 with X varying from 0, 5 and 15 mol% of TiO2 incorporated, identified as BRT0, BRT1 and BRT3, respectively, were used in this study. Scaffolds (pore sizes, 165-230 µm and porosity, 53.51-69.51%) were prepared using a polymer foam replication technique. BRT3 scaffolds exhibited higher compressive strength (7.16 ±â€¯0.22 MPa) when compared to BRT0 (6.02 ±â€¯0.47 MPa) and BRT1 (5.65 ±â€¯0.28 MPa) scaffolds with lower, or no, TiO2 content. The solubility of the scaffolds decreased as the TiO2 content increased up to 15 mol% when samples of each scaffold were immersed in DI water and the pH of all these extracts went up from 7.0 to 8.5 in 30 days. The cumulative ion release from the scaffolds showed significant difference with respect to TiO2 content; addition of 5 mol% TiO2 at the expense of borate (B2O3) decreased the ion release remarkably. Furthermore, it was found that for all three scaffolds, cumulative ion release increased with incubation time. The results indicate that the degradation rates and compressive strengths of borate bioactive glass scaffolds could be controlled by varying the amount of TiO2 incorporated, confirming their potential as scaffolds in TKA and rTKA.

A review of materials for managing bone loss in revision total knee arthroplasty.

In 2014-2015, 61,421 total knee arthroplasties (TKAs) were performed in Canada; an increase of about 20% over 2000-2001. Revision total knee arthroplasties (rTKAs) accounted for 6.8% of TKAs performed between 2014 and 2015, and this is estimated to grow another 12% by 2025. rTKAs are typically more complicated than primary TKAs due to the significant loss of femoral and tibial bone stock. The escalating demand and limitations associated with total knee arthroplasty and their revision drives the development of novel treatments. A variety of materials have been utilized to facilitate regeneration of healthy bone around the site of a knee arthroplasty. The selection of these materials is based on the bone defect size and includes bone grafts, graft substitutes and cements. However, all these materials have certain disadvantages such as blood loss, disease transmission (bone grafts), inflammatory response, insufficient mechanical properties (bone graft substitutes) thermal necrosis and stress shielding (bone cement). Recently, the use of metal augments for large bone defects has attracted attention, however they can undergo fretting, corrosion, and stress shielding. All things considered, this review indicates the necessity of developing augments that have structural integrities and biodegradation rates similar to that of human bone. Therefore, the future of bone loss management may lie in fabricating novel bioactive glass augments as they can promote bone healing and implant stability and can degrade with time.

Measurement of Adhesion of Sternal Wires to a Novel Bioactive Glass-Based Adhesive.

Stainless steel wires are the standard method for sternal closure because of their strength and rigidity, the simplicity of the process, and the short healing time that results from their application. Despite this, problems still exist with sternal stability due to micromotion between the two halves of the dissected and wired sternum. Recently, a novel glass-based adhesive was developed which, in cadaveric trials and in conjunction with wiring, was shown to restrict this micromotion. However, in order to avoid complications during resternotomy, the adhesive should adhere only to the bone and not the sternal wire. In this study, sternal wires were embedded in 8 mm discs manufactured from the novel glass-based adhesive and the constructs were then incubated at 37 °C for one, seven, and 30 days. The discs were manufactured in two different thicknesses: 2 and 3 mm. Wire pull-out tests were then performed on the constructs at three different strain rates (1, 0.1, and 0.01 mm/min). No statistically significant difference in pull-out force was found regardless of incubation time, loading rate, or construct thickness. The pull-out forces recorded were consistent with static friction between the wire and adhesive, rather than the adhesion between them. Scanning electron micrographs provided further proof of this. These results indicate that the novel adhesive may be suitable for sternal fixation without complicating a potential resternotomy.

Novel adhesives for sternal fixation and stabilization: A biomechanical analysis.

BACKGROUND: Cerclage wires remain the current standard of care following median sternotomy, despite significant complications including dehiscence and infection. This study uses a human cadaveric model to investigate the use of glass polyalkenoate cements formulated from two glasses, A (mole fraction: SiO2:0.48, ZnO:0.36, CaO:0.12, SrO:0.04) and B (mole fraction: SiO2:0.48, ZnO:0.355, CaO:0.06, SrO:0.08, P2O5:0.02, Ta2O5:0.005), to improve wired sternal fixation. METHODS: Median sternotomies were performed on fifteen cadaveric sterna. Fixation was performed with either traditional wire cerclage or adhesive-enhanced wire cerclage; the adhesive based on either Glass A or Glass B. Cyclic tensile loading of 10 N to 100 N was applied. Every 30 cycles, the maximum load was increased by 100 N up to a maximum of 500 N. Two adhered sterna were tested beyond 500 N. Mid-sternal displacement was measured to assess fixation stability. FINDINGS: Displacement for adhesive-enhanced sternal closures were significantly less (p < 0.05) than standard wire cerclage. There was no significant difference between adhesives. Up to 500 N, no adhesive-enhanced sternum experienced a pathological sternal displacement (>2 mm), while three out of five of traditional wire fixations did. Of the two adhered samples tested beyond 500 N, one showed pathological displacement at 800 N and the other at 1100 N. Failure of adhered sterna appeared to initiate within the trabecular bone rather than in the adhesive. INTERPRETATION: The adhesives were capable of providing immediate bone stability, significantly reducing sternal displacement. In vivo investigations are warranted to determine the effect the adhesives have on bone remodelling.

The effect of tantalum incorporation on the physical and chemical properties of ternary silicon-calcium-phosphorous mesoporous bioactive glasses.

Synthesis and characterization of the first mesoporous bioactive glasses (MBGs) containing tantalum are reported here, along with their potential application as hemostats. Silica MBGs were synthesized using with the molar composition of (80-x)% Si, 15% Ca, 5% P, and x% Ta. It was found that incorporation of >1 mol % Ta into the MBGs changes their physical and chemical properties. Increasing Ta content from 0 to 10 mol % causes a decrease in the surface area and pore volume of ~20 and ~35%, respectively. This is due to the increase in nonbridging oxygens and mismatch of thermal expansion coefficient which created discontinuities in the ordered channel structure. However, the effect is not significant on the amount of ions (Si, Ca, P, and Ta) released, from the sample into deionized water, for short durations (<60 min). In a mouse tail-cut model, a significant decrease in bleeding time (≥50% of average bleeding time) was found for Ta-MBGs compared to having no treatment, Arista, and MBG without Ta. Further studies are proposed to determine the mechanism of Ta involvement with the hemostatic process. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2229-2237, 2019.

Novel adhesives for distal radius fixation: A biomechanical analysis.

Wrist fractures can be difficult to treat due to advanced age of the patient, medical co-morbidities, and comminution of the bone. This study examines the effectiveness of two injectable glass polyalkenoate cements (GPCs), derived from two different glasses (A and B), as minimally invasive treatments for distal radius fractures. Twenty-seven fresh cadaveric radial pairs were tested either in compressive fatigue or to quasi-static compressive failure. The radii tested to failure had one pair fixated with a GPC while the other was left intact. The radii tested under fatigue had one pair fixated with a GPC and the other with a volar locking plate. A wedge osteotomy was used to simulate a severely comminuted fracture. When loaded to failure, the radii fixated with a GPC made from glass A or B were found to be, respectively, at least 57% and 62% as strong as their intact biological pair (95% Confidence Interval, Lower). Using a paired t-test, the radii fixated with either adhesive were found to be significantly stiffer than their biological pairs fixated with a volar locking plate for all cycles of fatigue loading. The adhesives under investigation demonstrate promise as treatment for distal radius fractures. In vivo investigations are warranted to determine the effect that the adhesives have on the bone remodelling process.

Well-ordered mesoporous silica and bioactive glasses: promise for improved hemostasis.

Immediate control of uncontrolled bleeding and infection are essential for saving lives in both combat and civilian arenas. Inorganic well-ordered mesoporous silica and bioactive glasses have recently shown great promise for accelerating hemostasis and infection control. However, to date, there has been no comprehensive report assessing their specific mechanism of action in accelerating the hemostasis process and exerting an antibacterial effect. After providing a brief overview of the hemostasis process, this review presents a critical overview of the recently developed inorganic mesoporous silica and bioactive glass-based materials proposed for hemostatic clinical applications and specifically investigates their unique characteristics that render them applicable for hemostatic applications and preventing infections. This article also identifies promising new research directions that should be undertaken to ascertain the effectiveness of these materials for hemostatic applications.

Incorporating Germanium Oxide into the Glass Phase of Novel Zinc/Magnesium-Based GPCs Designed for Bone Void Filling: Evaluating Their Physical and Mechanical Properties.

The structural role of Germanium (Ge), when substituting for Zinc (Zn) up to 8 mol % in the 0.48SiO2⁻0.12CaO⁻0.36ZnO⁻0.04MgO glass series, was investigated with respect to both the glass chemistry and also the properties of glass polyalkenoate cements (GPCs) manufactured from them. The Network connectivity (NC) of the glass was calculated to increase from 1.83 to 2.42 with the addition of GeO2 (0⁻8 mol %). Differential thermal analysis (DTA) results confirmed an increase in the glass transition temperature (Tg) of the glass series with GeO2 content. X-ray photoelectron spectroscopy (XPS) showed an increase in the ratio of bridging oxygens (BO) to non-bridging oxygens (NBO) with the addition of GeO2, supporting the NC and DTA results. 29Si magic angle spinning nuclear magnetic resonance spectroscopy (29Si MAS-NMR) determined a chemical shift from -80.3 to -83.7 ppm as the GeO2 concentration increased. These ionomeric glasses were subsequently used as the basic components in a series of GPCs by mixing them with aqueous polyacrylic acid (PAA). The handling properties of the GPCs resulting were evaluated with respect to the increasing concentration of GeO2 in the glass phase. It was found that the working times of these GPCs increased from 3 to 15 min, while their setting times increased from 4 to 18 min, facilitating the injectability of the Zn/Mg-GPCs through a 16-gauge needle. These Ge-Zn/Mg-GPCs were found to be injectable up to 96% within 12 min. Zn/Mg-GPCs containing GeO2 show promise as injectable cements for use in bone void filling.

Rapidly-Dissolving Silver-Containing Bioactive Glasses for Cariostatic Applications.

A novel bioactive glass series containing incremental amounts of silver oxide was synthesized, ground down, and subsequently incorporated into a dentifrice for the purpose of reducing the incidence of dental caries and lesion formation. Three glasses were synthesized using the melt quench route: Si-Control (70SiO2-12CaO-3P2O5-15Na2O, mol %), Si-02 and Si-05, where 0.2 and 0.5 mol % Ag2O were substituted, respectively, for SiO2 in Si-Control. The glasses were then ground, sieved, characterized, and dissolved in Tris buffer solution (pH = 7.30) for 6, 12, and 24 h, with the pH of the resultant solution being recorded and the ions that were released into solution quantified. Samples of each glass were subsequently embedded into a non-fluoridated, commercially available toothpaste which was then used to brush resin-mounted lamb molars which, up to the point of testing, had been stored in a 1.0 M HCl solution. Knoop microhardness measurements of the molars were recorded before and after brushing to determine the presence of remineralization on the surface of the teeth (surface hardness loss of 37%, 35%, and 34% for Si-Control, Si-02 and Si-05, respectively, after 24 h). Four oral cavity bacterial strains were isolated through swabs of the inner cheek, gums, and teeth surfaces of three volunteers, and placed on agar discs. Of each glass, 0.5 g was placed onto the discs, and the resultant inhibition zones were measured after 6, 12, and 24 h. Si-05 performed better than Si-02 on two strains after 24 h, while exhibiting similar behavior for the remaining two strains after 24 h; the largest inhibition zone measured was 2.8 mm, for Si-05 after 12 h. Si-Control exhibited no antibacterial effect at any time point, providing evidence for the role of silver oxide as the antibacterial component of these glasses.

A Preliminary Evaluation of the Ability of Keratotic Tissue to Act as a Prognostic Indicator of Hip Fracture Risk.

Studies have shown that Raman spectroscopic analysis of fingernail clippings can help differentiate between post-menopausal women who have and who have not suffered a fracture. However, all studies to date have been retrospective in nature, comparing the proteins in nails sourced from women, post-fracture. The objective of this study was to investigate the potential of a prospective test for hip fracture based on spectroscopic analysis of nail tissue. Archived toenail samples from post-menopausal women aged 50 to 63 years in the Nurses' Health Study were obtained and analysed by Raman spectroscopy. Nails were matched case-controls sourced from 161 women; 82 who underwent a hip fracture up to 20 years after nail collection and 81 age-matched controls. A number of clinical risk factors (CRFs) from the Fracture Risk Assessment (FRAX) tool had been assessed at toenail collection. Using 80% of the spectra, models were developed for increasing time periods between nail collection and fracture. Scores were calculated from these models for the other 20% of the sample and the ability of the score to predict hip fracture was tested in model with and without the CRFs by comparing the odds ratios (ORs) per 1 SD increase in standardised predictive values. The Raman score successfully distinguished between hip fracture cases and controls. With only the score as a predictor, a statistically significant OR of 2.2 (95% confidence interval [CI]: 1.5-3.1) was found for hip fracture for up to 20 years after collection. The OR increased to 3.8 (2.6-5.4) when the CRFs were added to the model. For fractures limited to 13 years after collection, the OR was 6.3 (3.0-13.1) for the score alone. The test based on Raman spectroscopy has potential for identifying individuals who may suffer hip fractures several years in advance. Higher powered studies are required to evaluate the predictive capability of this test.

Development of a novel bioactive glass suitable for osteosarcoma-related bone grafts.

In this study, zinc borate-based glasses with increasing gallium content (0, 2.5, 5, 10, and 15 wt % Ga) were synthesized and their effect on the viability and proliferation of preosteoblasts and osteosarcoma cancer cells were investigated. Methyl thiazolyl tetrazolium (MTT) cell viability assays using glass degradation extracts revealed that the extracts from glasses with lower Ga contents could enhance the viability of preosteoblasts, while extracts from the glass composition with 15 wt % Ga caused statistically significant reduction of their viability. MTT cell viability assays using the extracts and osteosarcoma cells showed that only extracts from the glass composition with 5 wt % Ga (G3) did not cause a statistically significant increase in the viability of cancer cells for all degradation periods (1 day, 7 days, and 28 days). G3 was selected as the most suitable composition for the osteosarcoma-related graft operations as it could improve the viability of preosteoblasts without increasing the viability of cancer cells. The viability of preosteoblasts and osteosarcoma cells in contact with the glass powders were also investigated using MTT assays. The results showed that the G3 powders could enhance the viability of preosteoblasts while decreasing the viability of osteosarcoma cells. Finally, live/dead assays revealed that suppression of proliferation appeared to be the mechanism causing the observed reductions in the viability of osteosarcoma cells exposed to G3 powders. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1186-1193, 2018.