The Use of Biomaterials in Internal Radiation Therapy

Radiotherapy has become one of the most prominent and effective modalities for cancer treatment and care. Ionising radiation, delivered either from external or internal sources, can be targeted to cancerous cells causing damage to DNA that can induce apoptosis. External beam radiotherapy delivers either photon radiation (x-rays or gamma rays) or particle radiation (neutrons or protons) in a targeted manner to specific tumour locations. Internal radiotherapy involves placing radioactive sources within the body to deliver localised doses of therapeutic radiation to tumours using short range radionuclides. Biomaterials have been developed to allow more precise targeting of radiotherapy in order to reduce toxicity to surrounding healthy tissues and increase treatment efficacy. These unique biomaterials have been developed from polymers, glasses and ceramics. Polymeric materials have been used to both displace healthy tissue from tumours receiving radiation, and to deliver radioactive sources into the body. These polymers can respond to various stimuli, such as radiation or reactive oxygen species, to deliver therapeutic payloads to target tissue during or post radiotherapy. Glass-based biomaterials doped with radionuclides have also been developed to provide in situ radiotherapy. Novel biomaterials that can enhance the synergistic effect of other treatment modalities, such as chemotherapy and immunotherapy, continue to be developed. Theranostic materials that are capable of providing diagnostic information whilst simultaneously delivering a therapeutic effect to enhance radiotherapy are also briefly reviewed

Rheological, Surface Tension and Conductivity Insights on the Electrospinnability of Poly(lactic-co-glycolic acid)-hyaluronic Acid Solutions and Their Correlations with the Nanofiber Morphological Characteristics

In this study, solutions were prepared with fixed concentrations of hyaluronic acid (HA) but varied concentrations of poly (lactic-co-glycolic acid) (PLGA) to emphasize the effects of PLGA concentration and HA addition on solution properties and to further evaluate their electrospinning performance. The dependence of specific viscosity on PLGA concentration was studied to determine the concentration regimes and evaluate the critical concentration (Ce) for successful fiber generation. The Ce of PLGA solutions is 12.07% compared to 10.09% for PLGA-HA solutions. Blending with HA results in a lower concentration dependence and better consistency to the theoretical scaling mechanisms due to the additional topological constrains, which thus result in more chain entanglements. Solutions in semi-dilute entangled regimes show the crossover of complex moduli, verifying the stable and reliable entanglement network. Higher concentrations and HA addition both led to lower crossover frequencies and, thus, a longer relaxation time. The effects of a higher PLGA concentration and HA addition on the surface tension were not evident. However, the HA addition significantly improved the solution conductivity up to three times in the pure PLGA solutions due to its polyelectrolyte nature. Defect-free and uniform nanofibers were generated from 35% to 40% of the PLGA-HA solutions, yet fibers with bead-on-string structures were produced from all studied pure PLGA solutions. Such solution characteristics and parametric correlations can provide predictive insights on tailoring the morphological characteristics of nanofibers for specific applications

Developing unique geometries of phosphate-based glasses and their prospective biomedical applications

© 2019 Johnson Matthey Phosphate-based glasses are promising materials for a range of applications including biomedical, veterinary and optical. These glasses are distinguished by the presence of at least one terminal oxygen atom, which gives phosphate-based glasses unique properties of which the most interesting is their easily controllable degradation profiles. This article describes the main structural features and applications of phosphate-based glass materials focusing primarily on biomedical applications. The processes utilised for developing varying geometries such as fibres, solid and porous microspheres and coatings are also explored

Developing unique geometries of phosphate-based glasses and their prospective biomedical applications

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L-DOPA coating improved phosphate glass fibre strength and fibre/matrix interface

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Live quantitative monitoring of mineral deposition in stem cells using tetracycline hydrochloride

The final stage of in vitro osteogenic differentiation is characterized by the production of mineral deposits containing calcium cations and inorganic phosphates, which populate the extracellular matrix surrounding the cell monolayer. Conventional histological techniques for the assessment of mineralization, such as Von Kossa and Alizarin Red S staining, are end-point techniques requiring cell fixation. Moreover, in both cases staining quantitation requires dye extraction which irreversibly alters the ECM conformation and structure, therefore preventing the use of the sample for further analysis. In this study, the use of Tetracycline hydrochloride (TC) is proposed for the non-destructive staining, quantitation and imaging of mineralizing bone-like nodules in live cultures of human bone marrow mesenchymal stem cells (MSCs) cultured under osteogenic conditions. Overnight administration of TC to living cells was shown not to alter the metabolic activity or the progression of cell differentiation. When applied to differentiating cultures, cell exposure to serial doses of TC was found to produce quantifiable fluorescence emission specifically in osteogenic cultures. Incubation with TC enabled fluorescence imaging of mineralised areas in live cultures and the combination with other fluorophores using appropriate filters. These results demonstrate that serial TC administration over the differentiation time course provides a qualitative and quantitative tool for the monitoring and evaluation of the differentiation process in live cells

One-step fabrication of superhydrophobic P(VDF-co-HFP) nanofibre membranes using electrospinning technique

© 2019 Wiley Periodicals, Inc. In this study, superhydrophobic electrospun P(VDF-co-HFP) membranes were fabricated in a one-step electrospinning process. The effects of the key parameters of electrospinning (solution concentration, electrical potential, flow rate, and solvent) on the surface roughness, fiber formation, and hydrophobicity of the membranes were evaluated using Taguchi method. A 4 × 3 orthogonal array was utilized, and the results indicated that the solvent played the critical role in producing the superhydrophobic nanofibre membranes. It was demonstrated that it is possible to produce superhydrophobic membranes with P(VDF-co-HFP) without additional functionalisation and fillers. The highest water contact angle and the lowest contact angle hysteresis obtained were 156° and 5°, respectively, and the roughness values varied from 0.15 to 5.74 μm for the produced P(VDF-co-HFP) nanofibre membranes. The surface superhydrophobicity of the membranes was attributed to the specific structures consisting of a combination of beads and nanofibres. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48817

Patient Perspectives on Use of Stem Cells to Treat Osteoporosis

Osteoporosis is a systemic skeletal disease leading to increased risk of fragility fractures. These fractures lead to significant patient morbidity, increased mortality and substantial health and social care costs. The use of stem cells for cell-based therapies is currently an exciting, promising and growing area for disease treatment and regenerative medicine. However, the attitudes of participants towards the use of stem cells for regenerative medicine applications, particularly for therapeutic interventions amongst the older population, have not been well explored. This study explored patient perceptions of a proposed new treatment utilising a novel orthobiologic stem cell therapy. An online questionnaire for participants affected b

Live Simultaneous Monitoring of Mineral Deposition and Lipid Accumulation in Differentiating Stem Cells

Mesenchymal stem cells (MSCs) are progenitors for bone-forming osteoblasts and lipid-storing adipocytes, two major lineages co-existing in bone marrow. When isolated in vitro, these stem cells recapitulate osteoblast or adipocyte formation if treated with specialised media, modelling how these lineages interact in vivo. Osteogenic differentiation is characterised by mineral deposits accumulating in the extracellular matrix, typically assessed using histological techniques. Adipogenesis occurs with accumulation of intracellular lipids that can be routinely visualised by Oil Red O staining. In both cases, staining requires cell fixation and is thus limited to end-point assessments. Here, a vital staining approach was developed to simultaneously detect mineral deposits and lipid droplets in differentiating cultures. Stem cells induced to differentiate produced mixed cultures containing adipocytes and bone-like nodules, and after two weeks live cultures were incubated with tetracycline hydrochloride and Bodipy to label mineral- and lipid-containing structures, respectively. Fluorescence microscopy showed the simultaneous visualisation of mineralised areas and lipid-filled adipocytes in live cultures. Combined with the nuclear stain Hoechst 33258, this approach further enabled live confocal imaging of adipogenic cells interspersed within the mineralised matrix. This multiplex labelling was repeated at subsequent time-points, demonstrating the potential of this new approach for the real-time high-precision imaging of live stem cells

Formulating injectable pastes of porous calcium phosphate glass microspheres for bone regeneration applications

Current trends in regenerative medicine treatments for bone repair applications focus on cell-based therapies. These aim to deliver the treatment via a minimally invasive injection to reduce patient trauma and to improve efficacy. This paper describes the injectability of porous calcium phosphate glass microspheres to be used for bone repair based on their formulation, rheology and flow behavior. The use of excipients (xanthan gum, methyl cellulose and carboxyl methyl cellulose) were investigated to improve flow performance. Based on our results, the flow characteristics of the glass microsphere pastes vary according to particle size, surface area, and solid to liquid ratio, as well as the concentration of viscosity modifiers used. The optimal flow characteristics of calcium phosphate glass microsphere pastes was found to contain 40 mg/mL of xanthan gum which increased viscosity whilst providing elastic properties (∼29,000 Pa) at shear rates that mirror the injection process and the resting period post injection, preventing the glass microspheres from both damage and dispersion. It was established that a base formulation must contain 1 g of glass microspheres (60–125 μm in size) per 1 mL of cell culture media, or 0.48 g of glass microspheres of sizes between 125 and 200 μm. Furthermore, the glass microsphere formulations with xanthan gum were readily injectable via a syringe-needle system (3–20 mL, 18G and 14G needles), and have the potential to be utilized as a cell (or other biologics) delivery vehicle for bone regeneration applications