Extensively Microtwinned Diamond with Nanolaminates of Lonsdaleite Formed by Flash Laser Heating of Glassy Carbon.

Diamond's unique properties on the nanoscale make it one of the most important materials for use in biosensors and quantum computing and for components that can withstand the harsh environments of space. We synthesize oriented, faceted diamond particles by flash laser heating of glassy carbon at 16 GPa and 2300 K. Detailed transmission electron microscopy shows them to consist of a mosaic of diamond nanocrystals frequently joined at twin boundaries forming microtwins. Striking 3-fold translational periodicity was observed in both imaging and diffraction. This periodicity was shown to originate from nanodimensional wedge-shaped overlapping regions of twinned diamond and not from a possible 9R polytype, which has also been reported in other group IVa elements and water ice. Extended bilayers of hexagonal layer stacking were observed, forming lonsdaleite nanolaminates. The particles exhibited optical fluorescence with a rapid quench time (<1 ns) attributed to their unique twinned microstructure.

Investigation of Room Temperature Formation of the Ultra-Hard Nanocarbons Diamond and Lonsdaleite.

Diamond is an attractive material due to its extreme hardness, high thermal conductivity, quantum optical, and biomedical applications. There is still much that is not understood about how diamonds form, particularly at room temperature and without catalysts. In this work, a new route for the formation of nanocrystalline diamond and the diamond-like phase lonsdaleite is presented. Both diamond phases are found to form together within bands with a core-shell structure following the high pressure treatment of a glassy carbon precursor at room temperature. The crystallographic arrangements of the diamond phases revealed that shear is the driving force for their formation and growth. This study gives new understanding of how shear can lead to crystallization in materials and helps elucidate how diamonds can form on Earth, in meteorite impacts and on other planets. Finally, the new shear induced formation mechanism works at room temperature, a key finding that may enable diamond and other technically important nanomaterials to be synthesized more readily.

Covalent Immobilization of N-Acetylcysteine on a Polyvinyl Chloride Substrate Prevents Bacterial Adhesion and Biofilm Formation.

Biofilm formation and antimicrobial resistance at surgical implant sites result in high morbidity and mortality. Identifying novel molecules that inhibit biofilm formation to coat surgical biomaterials is essential. One such compound is N-acetylcysteine (NAC), a potent antioxidant precursor for glutathione, necessary in mammalian cells and known to disrupt/prevent biofilms. In this study, NAC was covalently immobilized onto functionalized polyvinyl chloride surfaces using plasma immersion ion implantation (PIII) treatment that achieves covalent binding without the need for linker groups. NAC immobilization was characterized using water contact angles, Fourier-transform infrared, and X-ray photoelectron spectroscopy techniques. Bacterial viability and biofilm formation on NAC surfaces were assessed using resazurin assays, phase contrast microscopy, and colony counting experiments. Effect of NAC on bacterial polysaccharide production and DNA cleaving was investigated using the phenol-sulfuric acid method and the Qubit fluorometer. Surface thermodynamics between the NAC coating and bacterial cells were measured using the Lewis acid-base method. Surface characterization techniques demonstrated superficial changes after PIII treatment and subsequent covalent NAC immobilization. NAC-coated surfaces significantly reduced biofilm viability and the presence of Gram-negative and Gram-positive bacteria. NAC also decreased polysaccharide production and degraded DNA. This led to unfavorable conditions for biofilm formation on NAC-coated surfaces, as demonstrated by surface thermodynamic analysis. NAC-coated surfaces showed no cytotoxicity to human fibroblast cells. This study has successfully utilized NAC as an antibiofilm coating, which may pave the way for improved prophylactic coatings on medical implant devices in the future.

Tin oxide artificial synapses for low power temporal information processing.

Lateral memristors configured with inert Pt contacts and mixed phase tin oxide layers have exhibited immediate, forming-free, low-power bidirectional resistance switching. Activity dependent conductance and relaxation in the low resistance state resembled short term potentiation in biological synapses. After scanning probe microscopy, x-ray photoelectron spectroscopy and electrical measurements, the device characteristics were attributed to Joule heating induced decomposition of the minority SnO phase and formation of a SnO2 conducting filament with higher effective n-type doping. Finally, the devices recognized input voltage pulse sequences and spectral data by returning unique conductance states, suggesting suitability for bio-inspired pattern recognition systems.

Linker-protein G mediated functionalization of polystyrene-encapsulated upconversion nanoparticles for rapid gene assay using convective PCR.

The authors report on a simplified approach to encapsulate upconversion nanoparticles (UCNPs) in polystyrene spheres by mini-emulsion polymerisation. The resulting particles (PS-UCNP) are hydrophilic, stable and suitable for biomolecular recognition and biosensing applications. Also, a strategy was developed for bioconjugation of antibodies onto the surface of the PS-UCNPs by using the bifunctional fusion protein linker-protein G (LPG). LPG mediates the functionalisation of PS-UCNPs with antibodies against digoxigenin allowing for specific labelling of convective PCR (cPCR) amplicons. Lambda DNA was amplified using cPCR on a heat block for 30 min using the digoxigenin labelled forward and biotin labelled reverse primers. The antibody functionalised PS-UCNPs bind to the digoxigenin end of the cPCR amplicons. Finally, the streptavidin labelled magnetic beads were used to selectively capture the PS-UCNP-labelled cPCR amplicons and the upconversion signal was detected at 537 nm under 980 nm excitation. This sandwich approach enables direct recognition of the target lambda DNA with a detection limit of 103 copies µL-1. The upconversion signal decreased proportionally to the concentration of the lambda DNA with a linear response between 107 and 103 copies of DNA. Graphical abstract Schematic representation of polystyrene-encapsulated upconversion nanoparticles (PS-UCNPs) prepared by mini-emulsion polymerisation. The PS-UCNPs were functionalised with anti-digoxigenin antibody using the fusion protein linker-protein G (LPG). Detection of digoxigenin-labelled amplicons is achieved (a) by using the antibody-functionalised LPG@PS-UCNP labels; (b) magnetic separation, and (c) 980 nm laser light for detection of the green upconversion luminescence peaking at 537 nm.

Models for the bystander effect in gradient radiation fields: Range and signalling type.

Bystander responses to radiation are responsible for a significant fraction of cell death, but are not included in the conventional linear-quadratic (LQ) radiobiological model. Strong dose gradients in radiation fields affect the distribution of bystander signals and can be used to decrease the survival of cancer cells. Predictive models incorporating bystander effects are needed to design the dose gradients in modulated fields to improve cancer treatments. Fundamental questions concern the nature and range of bystander signalling. Some authors propose bystander signals are carried by diffusing molecular factors expressed into the extracellular medium and that strong dose gradients drive their diffusion. Others propose bystander effects occur between neighbouring cells through gap-junctions, leaving no universal agreement. Here we test three assumptions concerning the effective range of bystander signals using both average and local measures of survival. Model 1 assumes short range signalling (e.g. gap-junction mediated) proportional to the local dose gradient, without relying on diffusion across the extracellular medium; Model 2 assumes metabolite diffusion governed by Fick's second law with either negative or both signs of bystander effect; Model 3 assumes that the extent of signal production is dependent on the average of the dose gradient over the field and that the signals have long range distribution. A single bystander parameter for each model was fitted to observed average survival of cancer cells in uniform and modulated fields. All models gave better fits than the classical LQ model. Model 2 fitted best with one sign of bystander effect on survival. Model 3 gave the best overall fit of average survival. The models were then used to predict local survival and survival as a function of dose in modulated fields, using independent datasets, without changing the bystander parameter. Model 3 gave the best overall prediction. This study demonstrates that the bystander effect can be controlled by design of the radiation field modulation.

Plasma processing of PDMS based spinal implants for covalent protein immobilization, cell attachment and spreading.

PDMS is widely used for prosthetic device manufacture. Conventional ion implantation is not a suitable treatment to enhance the biocompatibility of poly dimethyl siloxane (PDMS) due to its propensity to generate a brittle silicon oxide surface layer which cracks and delaminates. To overcome this limitation, we have developed new plasma based processes to balance the etching of carbon with implantation of carbon from the plasma source. When this carbon was implanted from the plasma phase it resulted in a surface that was structurally similar and intermixed with the underlying PDMS material and not susceptible to delamination. The enrichment in surface carbon allowed the formation of carbon based radicals that are not present in conventional plasma ion immersion implantation (PIII) treated PDMS. This imparts the PDMS surfaces with covalent protein binding capacity that is not observed on PIII treated PDMS. The change in surface energy preserved the function of bound biomolecules and enhanced the attachment of MG63 osteosarcoma cells compared to the native surface. The attached cells, an osteoblast interaction model, showed increased spreading on the treated over untreated surfaces. The carbon-dependency for these beneficial covalent protein and cell linkage properties was tested by incorporating carbon from a different source. To this end, a second surface was produced where carbon etching was balanced against implantation from a thin carbon-based polymer coating. This had similar protein and cell-binding properties to the surfaces generated with carbon inclusion in the plasma phase, thus highlighting the importance of balancing carbon etching and deposition. Additionally, the two effects of protein linkage and bioactivity could be combined where the cell response was further enhanced by covalently tethering a biomolecule coating, as exemplified here with the cell adhesive protein tropoelastin. Providing a balanced carbon source in the plasma phase is applicable to prosthetic device fabrication as illustrated using a 3-dimensional PDMS balloon prosthesis for spinal implant applications. Consequently, this study lays the groundwork for effective treatments of PDMS to selectively recruit cells to implantable PDMS fabricated biodevices.

Grid therapy using high definition multileaf collimators: realizing benefits of the bystander effect.

BACKGROUND: In microbeam radiotherapy (MRT), parallel arrays of high-intensity synchrotron x-ray beams achieve normal tissue sparing without compromising tumor control. Grid-therapy using clinical linacs has spatial modulation on a larger scale and achieves promising results for palliative treatments of bulky tumors. The availability of high definition multileaf collimators (HDMLCs) with 2.5 mm leaves provides an opportunity for grid-therapy to more closely approach MRT. However, challenges to the wider implementation of grid-therapy remain because spatial modulation of the target volume runs counter to current radiotherapy practice and mechanisms for the beneficial effects of MRT are not fully understood. Without more knowledge of cell dose responses, a quantitative basis for planning treatments is difficult. The aim of this study is to determine if therapeutic benefits of MRT can be achieved using a linac with HDMLCs and if so, to develop a predictive model to support treatment planning. MATERIAL AND METHODS: HD120-MLCs of a Varian Novalis TXTM were used to generate grid patterns of 2.5 and 5.0 mm spacing, which were characterized dosimetrically using GafchromicTM EBT3 film. Clonogenic survival of normal (HUVEC) and cancer (NCI-H460, HCC-1954) cell lines following irradiation under the grid and open fields using a 6 MV photon beam were compared in-vitro for the same average dose. RESULTS AND CONCLUSIONS: Relative to an open field, survival of normal cells in a 2.5 mm striped field was the same, while the survival of both cancer cell lines was significantly lower. A mathematical model was developed to incorporate dose gradients of the spatial modulation into the standard linear quadratic model. Our new bystander extended LQ model assumes spatial gradients drive the diffusion of soluble factors that influence survival through bystander effects, successfully predicting the experimental results that show an increased therapeutic ratio. Our results challenge conventional radiotherapy practice and propose that additional gain can be realized by prescribing spatially modulated treatments to harness the bystander effect.

The physics of confined flow and its application to water leaks, water permeation and water nanoflows: a review.

This review assesses the current state of understanding of the calculation of the rate of flow of gases, vapours and liquids confined in channels, in porous media and in permeable materials with an emphasis on the flow of water and its vapour. One motivation is to investigate the relation between the permeation rate of moisture and that of a noncondensable test gas such as helium, another is to assist in unifying theory and experiment across disparate fields. Available theories of single component ideal gas flows in channels of defined geometry (cylindrical, rectangular and elliptical) are described and their predictions compared with measurement over a wide range of conditions defined by the Knudsen number. Theory for two phase flows is assembled in order to understand the behaviour of four standard water leak configurations: vapour, slug, Washburn and liquid flow, distinguished by the number and location of phase boundaries (menisci). Air may or may not be present as a background gas. Slip length is an important parameter that greatly affects leak rates. Measurements of water vapour flows confirm that water vapour shows ideal gas behaviour. Results on carbon nanotubes show that smooth walls may lead to anomalously high slip lengths arising from the properties of 'confined' water. In porous media, behaviour can be matched to the four standard leaks. Traditional membrane permeation models consider that the permeant dissolves, diffuses and evaporates at the outlet side, ideas we align with those from channel flow. Recent results on graphite oxide membranes show examples where helium which does not permeate while at the same time moisture is almost unimpeded, again a result of confined water. We conclude that while there is no a priori relation between a noncondensable gas flow and a moisture flow, measurements using helium will give results within two orders of magnitude of the moisture flow rate, except in the case where there is anomalous slip or confined water, when moisture specific measurements are essential.

Small field detector correction factors: effects of the flattening filter for Elekta and Varian linear accelerators.

Flattening filter-free (FFF) beams are becoming the preferred beam type for stereotactic radiosurgery (SRS) and stereotactic ablative radiation therapy (SABR), as they enable an increase in dose rate and a decrease in treatment time. This work assesses the effects of the flattening filter on small field output factors for 6 MV beams generated by both Elekta and Varian linear accelerators, and determines differences between detector response in flattened (FF) and FFF beams. Relative output factors were measured with a range of detectors (diodes, ionization cham-bers, radiochromic film, and microDiamond) and referenced to the relative output factors measured with an air core fiber optic dosimeter (FOD), a scintillation dosimeter developed at Chris O'Brien Lifehouse, Sydney. Small field correction factors were generated for both FF and FFF beams. Diode measured detector response was compared with a recently published mathematical relation to predict diode response corrections in small fields. The effect of flattening filter removal on detector response was quantified using a ratio of relative detector responses in FFF and FF fields for the same field size. The removal of the flattening filter was found to have a small but measurable effect on ionization chamber response with maximum deviations of less than ± 0.9% across all field sizes measured. Solid-state detectors showed an increased dependence on the flattening filter of up to ± 1.6%. Measured diode response was within ± 1.1% of the published mathematical relation for all fields up to 30 mm, independent of linac type and presence or absence of a flattening filter. For 6 MV beams, detector correction factors between FFF and FF beams are interchangeable for a linac between FF and FFF modes, providing that an additional uncertainty of up to ± 1.6% is accepted.

Science of Water Leaks: Validated Theory for Moisture Flow in Microchannels and Nanochannels.

Water is ubiquitous; the science of its transport in micro- and nanochannels has applications in electronics, medicine, filtration, packaging, and earth and planetary science. Validated theory for water vapor and two-phase water flows is a "missing link"; completing it enables us to define and quantify flow in a set of four standard leak configurations with dimensions from the nanoscale to the microscale. Here we report the first measurements of water vapor flow rates through four silica microchannels as a function of humidity, including under conditions when air is present as a background gas. An important finding is that the tangential momentum accommodation coefficient (TMAC) is strongly modified by surface layers of adsorbed water molecules, in agreement with previous work on the TMAC for nitrogen molecules impacting a silica surface in the presence of moisture. We measure enhanced flow rates for two-phase flows in silica microchannels driven by capillary filling. For the measurement of flows in nanochannels we use heavy water mass spectrometry. We construct the theory for the flow rates of the dominant modes of water transport through each of the four standard configurations and benchmark it against our new measurements in silica and against previously reported measurements for nanochannels in carbon nanotubes, carbon nanopipes, and porous alumina. The findings show that all behavior can be described by the four standard leak configurations and that measurements of leak behavior made using other molecules, such as helium, are not reliable. Single-phase water vapor flow is overestimated by a helium measurement, while two-phase flows are greatly underestimated for channels larger than 100 nm or for all channels when boundary slip applies, to an extent that depends on the slip length for the liquid-phase flows.

Free radical functionalization of surfaces to prevent adverse responses to biomedical devices.

Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surfaces do not induce denaturation of immobilized protein but exhibit a low binding affinity for protein. Here, we describe an energetic ion-assisted plasma process that can make any surface hydrophilic and at the same time enable it to covalently immobilize functional biological molecules. We show that the modification creates free radicals that migrate to the surface from a reservoir beneath. When they reach the surface, the radicals form covalent bonds with biomolecules. The kinetics and number densities of protein molecules in solution and free radicals in the reservoir control the time required to form a full protein monolayer that is covalently bound. The shelf life of the covalent binding capability is governed by the initial density of free radicals and the depth of the reservoir. We show that the high reactivity of the radicals renders the binding universal across all biological macromolecules. Because the free radical reservoir can be created on any solid material, this approach can be used in medical applications ranging from cardiovascular stents to heart-lung machines.

Protecting Orthopaedic Implants from Infection: Antimicrobial Peptide Mel4 Is Non-Toxic to Bone Cells and Reduces Bacterial Colonisation When Bound to Plasma Ion-Implanted 3D-Printed PAEK Polymers.

Even with the best infection control protocols in place, the risk of a hospital-acquired infection of the surface of an implanted device remains significant. A bacterial biofilm can form and has the potential to escape the host immune system and develop resistance to conventional antibiotics, ultimately causing the implant to fail, seriously impacting patient well-being. Here, we demonstrate a 4 log reduction in the infection rate by the common pathogen S. aureus of 3D-printed polyaryl ether ketone (PAEK) polymeric surfaces by covalently binding the antimicrobial peptide Mel4 to the surface using plasma immersion ion implantation (PIII) treatment. The surfaces with added texture created by 3D-printed processes such as fused deposition-modelled polyether ether ketone (PEEK) and selective laser-sintered polyether ketone (PEK) can be equally well protected as conventionally manufactured materials. Unbound Mel4 in solution at relevant concentrations is non-cytotoxic to osteoblastic cell line Saos-2. Mel4 in combination with PIII aids Saos-2 cells to attach to the surface, increasing the adhesion by 88% compared to untreated materials without Mel4. A reduction in mineralisation on the Mel4-containing surfaces relative to surfaces without peptide was found, attributed to the acellular portion of mineral deposition.

A Preclinical Trial Protocol Using an Ovine Model to Assess Scaffold Implant Biomaterials for Repair of Critical-Sized Mandibular Defects.

The present work describes a preclinical trial (in silico, in vivo and in vitro) protocol to assess the biomechanical performance and osteogenic capability of 3D-printed polymeric scaffolds implants used to repair partial defects in a sheep mandible. The protocol spans multiple steps of the medical device development pipeline, including initial concept design of the scaffold implant, digital twin in silico finite element modeling, manufacturing of the device prototype, in vivo device implantation, and in vitro laboratory mechanical testing. First, a patient-specific one-body scaffold implant used for reconstructing a critical-sized defect along the lower border of the sheep mandible ramus was designed using on computed-tomographic (CT) imagery and computer-aided design software. Next, the biomechanical performance of the implant was predicted numerically by simulating physiological load conditions in a digital twin in silico finite element model of the sheep mandible. This allowed for possible redesigning of the implant prior to commencing in vivo experimentation. Then, two types of polymeric biomaterials were used to manufacture the mandibular scaffold implants: poly ether ether ketone (PEEK) and poly ether ketone (PEK) printed with fused deposition modeling (FDM) and selective laser sintering (SLS), respectively. Then, after being implanted for 13 weeks in vivo, the implant and surrounding bone tissue was harvested and microCT scanned to visualize and quantify neo-tissue formation in the porous space of the scaffold. Finally, the implant and local bone tissue was assessed by in vitro laboratory mechanical testing to quantify the osteointegration. The protocol consists of six component procedures: (i) scaffold design and finite element analysis to predict its biomechanical response, (ii) scaffold fabrication with FDM and SLS 3D printing, (iii) surface treatment of the scaffold with plasma immersion ion implantation (PIII) techniques, (iv) ovine mandibular implantation, (v) postoperative sheep recovery, euthanasia, and harvesting of the scaffold and surrounding host bone, microCT scanning, and (vi) in vitro laboratory mechanical tests of the harvested scaffolds. The results of microCT imagery and 3-point mechanical bend testing demonstrate that PIII-SLS-PEK is a promising biomaterial for the manufacturing of scaffold implants to enhance the bone-scaffold contact and bone ingrowth in porous scaffold implants. MicroCT images of the harvested implant and surrounding bone tissue showed encouraging new bone growth at the scaffold-bone interface and inside the porous network of the lattice structure of the SLS-PEK scaffolds.

Novel Sheep Model to Assess Critical-Sized Bone Regeneration with Periosteum for In Vivo Bioreactors.

Considerable research is being undertaken to develop novel biomaterials-based approaches for surgical reconstruction of bone defects. This extends to three-dimensional (3D) printed materials that provide stable, structural, and functional support in vivo. However, few preclinical models can simulate in vivo human biological conditions for clinically relevant testing. In this study we describe a novel ovine model that allows evaluation of in vivo osteogenesis via contact with bone and/or periosteum interfaced with printed polymer bioreactors loaded with biomaterial bone substitutes. The infraspinous scapular region of 14 Dorset cross sheep was exposed. Vascularized periosteum was elevated either attached to the infraspinatus muscle or separately. In both cases, the periosteum was supplied by the periosteal branch of the circumflex scapular vessels. In eight sheep, a 3D printed 4-chambered polyetheretherketone bioreactor was wrapped circumferentially in vascularized periosteum. In 6 sheep, 12 double-sided 3D printed 2-chambered polyetherketone bioreactors were secured to the underlying bone allowing direct contact with the bone on one side and periosteum on the other. Our model enabled simultaneous testing of up to 24 (12 double-sided) 10 × 10 × 5 mm bioreactors per scapula in the flat contact approach or a single 40 × 10 mm four-chambered bioreactor per scapula using the periosteal wrap. De novo bone growth was evaluated using histological and radiological analysis. Of importance, the experimental model was well tolerated by the animals and provides a versatile approach for comparing the osteogenic potential of cambium on the bone surface and elevated with periosteum. Furthermore, the periosteal flaps were sufficiently large for encasing bioreactors containing biomaterial bone substitutes for applications such as segmental mandibular reconstruction.

Neuromorphic sensing of biomolecules covalently immobilised on polydimethyl glutarimide.

Polydimethyl glutarimide (PMGI) layers with sub-micron thicknesses have been modified in a 2.5 kV Ar plasma immersion ion implantation (PIII) process to introduce free radical covalent binding sites. The surface roughness of the PMGI increased after the PIII treatment but no through-layer defects were observed. When applied to the treated PMGI, horseradish peroxidase (HRP) enzyme remained bound to the surface after extended immersion in sodium dodecyl sulfate solution (SDS). Hence, covalent binding between the activated surface and enzyme was confirmed. This covalent binding was achieved up to 24-h after the PIII process. The treated PMGI was then incorporated as a gate dielectric layer within a lateral three-terminal electrolyte-gated device. The device output characteristics resembled those of post-synaptic outputs; as successive (pre-synaptic) voltage pulses were applied to the gate, paired pulse depression and spike rate dependent plasticity were observed in the source-drain (post-synaptic) current. These characteristics were altered by the presence of HRP immobilised on the plasma-modified PMGI gate dielectric layer thus providing readout detection. These results and preliminary device characteristics show the potential for the plasma functionalized PMGI as a sensitive and reproducible biosensing technology.

An omics approach to delineating the molecular mechanisms that underlie the biological effects of physical plasma.

The use of physical plasma to treat cancer is an emerging field, and interest in its applications in oncology is increasing rapidly. Physical plasma can be used directly by aiming the plasma jet onto cells or tissue, or indirectly, where a plasma-treated solution is applied. A key scientific question is the mechanism by which physical plasma achieves selective killing of cancer over normal cells. Many studies have focused on specific pathways and mechanisms, such as apoptosis and oxidative stress, and the role of redox biology. However, over the past two decades, there has been a rise in omics, the systematic analysis of entire collections of molecules in a biological entity, enabling the discovery of the so-called "unknown unknowns." For example, transcriptomics, epigenomics, proteomics, and metabolomics have helped to uncover molecular mechanisms behind the action of physical plasma, revealing critical pathways beyond those traditionally associated with cancer treatments. This review showcases a selection of omics and then summarizes the insights gained from these studies toward understanding the biological pathways and molecular mechanisms implicated in physical plasma treatment. Omics studies have revealed how reactive species generated by plasma treatment preferentially affect several critical cellular pathways in cancer cells, resulting in epigenetic, transcriptional, and post-translational changes that promote cell death. Finally, this review considers the outlook for omics in uncovering both synergies and antagonisms with other common cancer therapies, as well as in overcoming challenges in the clinical translation of physical plasma.

A Comparison of In Vivo Bone Tissue Generation Using Calcium Phosphate Bone Substitutes in a Novel 3D Printed Four-Chamber Periosteal Bioreactor.

Autologous bone replacement remains the preferred treatment for segmental defects of the mandible; however, it cannot replicate complex facial geometry and causes donor site morbidity. Bone tissue engineering has the potential to overcome these limitations. Various commercially available calcium phosphate-based bone substitutes (Novabone®, BioOss®, and Zengro®) are commonly used in dentistry for small bone defects around teeth and implants. However, their role in ectopic bone formation, which can later be applied as vascularized graft in a bone defect, is yet to be explored. Here, we compare the above-mentioned bone substitutes with autologous bone with the aim of selecting one for future studies of segmental mandibular repair. Six female sheep, aged 7-8 years, were implanted with 40 mm long four-chambered polyether ether ketone (PEEK) bioreactors prepared using additive manufacturing followed by plasma immersion ion implantation (PIII) to improve hydrophilicity and bioactivity. Each bioreactor was wrapped with vascularized scapular periosteum and the chambers were filled with autologous bone graft, Novabone®, BioOss®, and Zengro®, respectively. The bioreactors were implanted within a subscapular muscle pocket for either 8 weeks (two sheep), 10 weeks (two sheep), or 12 weeks (two sheep), after which they were removed and assessed by microCT and routine histology. Moderate bone formation was observed in autologous bone grafts, while low bone formation was observed in the BioOss® and Zengro® chambers. No bone formation was observed in the Novabone® chambers. Although the BioOss® and Zengro® chambers contained relatively small amounts of bone, endochondral ossification and retained hydroxyapatite suggest their potential in new bone formation in an ectopic site if a consistent supply of progenitor cells and/or growth factors can be ensured over a longer duration.

Real-time scintillation array dosimetry for radiotherapy: the advantages of photomultiplier detectors.

PURPOSE: In this paper, a photomultiplier tube (PMT) array dosimetry system has been developed and tested for the real-time readout of multiple scintillation signals from fiber optic dosimeters. It provides array dosimetry with the advantages in sensitivity provided by a PMT, but without the need for a separate PMT for each detector element. METHODS: The PMT array system consisted of a multianode PMT, a multichannel data acquisition system, housing and optic fiber connections suitable for clinical use. The reproducibility, channel uniformity, channel crosstalk, acquisition speed, and sensitivity of the PMT array were quantified using a constant light source. Its performance was compared to other readout systems used in scintillation dosimetry. An in vivo HDR brachytherapy treatment was used as an example of a clinical application of the dosimetry system to the measurement of dose at multiple sites in the rectum. The PMT array system was also tested in the pulsed beam of a linear accelerator to test its response speed and its application with two separate methods of Cerenkov background removal. RESULTS: The PMT array dosimetry system was highly reproducible with a measurement uncertainty of 0.13% for a 10 s acquisition period. Optical crosstalk between neighboring channels was accounted for by omitting every second channel. A mathematical procedure was used to account for the crosstalk in next-neighbor channels. The speed and sensitivity of the PMT array system were found be superior to CCD cameras, allowing for measurement of more rapid changes in dose rate. This was further demonstrated by measuring the dose delivered by individual photon pulses of a linear accelerator beam. CONCLUSIONS: The PMT array system has advantages over CCD camera-based systems for the readout of scintillation light. It provided a more sensitive, more accurate, and faster response to meet the demands of future developments in treatment delivery.

Optimisation of exposure conditions for in vitro radiobiology experiments.

Despite the long history of using cell cultures in vitro for radiobiological studies, there is to date no study specifically addressing the dosimetric implications of flask selection and exposure environment in clonogenic assays. The consequent variability in dosimetry between laboratories impedes the comparison of results. In this study we compare the dose to cells adherent to the base of three types of commonly used culture flasks or plates. The cells are exposed to a 6MV clinical photon beam using either an open or a half blocked field. The depth of medium in each flask is varied with the medium surrounding the flask either water or air. The results show that the dose to the cells is more affected by the scattering conditions surrounding the flasks than by the level of filling within the flask. It is recommended that water or a water equivalent phantom material is used to surround the flasks or plates to approximate full scatter conditions at the cell layer. However for modulated fields, surrounding the 24 well plates with water-equivalent material is inadequate because of the large volume of air surrounding individual wells. Our results stress the importance of measuring the dose for new experimental configurations.