Biological scaffolds generated from tissue-derived extracellular matrix (ECM) are commonly used clinically for soft tissue regeneration. Such biomaterials can enhance tissue-specific differentiation ...of adult stem cells, suggesting that structuring different ECMs into multi-layered scaffolds can form the basis of new strategies for regenerating damaged interfacial tissues such as the osteochondral unit. In this study, mass spectrometry is used to demonstrate that growth plate (GP) and articular cartilage (AC) ECMs contain a unique array of regulatory proteins that may be particularly suited to bone and cartilage repair respectively. Applying a novel iterative freeze-drying method, porous bi-phasic scaffolds composed of GP ECM overlaid by AC ECM are fabricated, which are capable of spatially directing stem cell differentiation in vitro, promoting the development of graded tissues transitioning from calcified cartilage to hyaline-like cartilage. Evaluating repair 12-months post-implantation into critically-sized caprine osteochondral defects reveals that these scaffolds promote regeneration in a manner distinct to commercial control-scaffolds. The GP layer supports endochondral bone formation, while the AC layer stimulates the formation of an overlying layer of hyaline cartilage with a collagen fiber architecture better recapitulating the native tissue. These findings support the use of a bi-layered, tissue-specific ECM derived scaffolds for regenerating spatially complex musculoskeletal tissues.
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The ability of nano‐hydroxyapatite (nHA) particles developed in‐house to act as non‐viral delivery vectors is assessed. These nHA particles are combined with collagen to yield bioactive, ...biodegradable collagen nano‐hydroxyapatite (coll‐nHA) scaffolds. Their ability to act as gene‐activated matrices for BMP2 delivery is demonstrated with successful transfection of mesenchymal stem cells (MSCs) resulting in high calcium production.
Emerging infectious diseases (EIDs) of plants continue to devastate ecosystems and livelihoods worldwide. Effective management requires surveillance to detect epidemics at an early stage. However, ...despite the increasing use of risk-based surveillance programs in plant health, it remains unclear how best to target surveillance resources to achieve this. We combine a spatially explicit model of pathogen entry and spread with a statistical model of detection and use a stochastic optimisation routine to identify which arrangement of surveillance sites maximises the probability of detecting an invading epidemic. Our approach reveals that it is not always optimal to target the highest-risk sites and that the optimal strategy differs depending on not only patterns of pathogen entry and spread but also the choice of detection method. That is, we find that spatial correlation in risk can make it suboptimal to focus solely on the highest-risk sites, meaning that it is best to avoid 'putting all your eggs in one basket'. However, this depends on an interplay with other factors, such as the sensitivity of available detection methods. Using the economically important arboreal disease huanglongbing (HLB), we demonstrate how our approach leads to a significant performance gain and cost saving in comparison with conventional methods to targeted surveillance.
The use of collagen-based scaffolds in orthopedic applications has been limited due to poor mechanical properties, but this may be overcome by the introduction of a stiffer supporting phase. Thus, we ...developed a synthesis technique to produce nonaggregating, stable nanohydroxyapatite (nHA) particles, permitting the fabrication of biomimetic-inspired scaffolds through the combination of nanosized HA with collagen, as found in native bone. This study evaluates the mechanical and biological impact of incorporating increasing concentrations of these nanoparticles into porous collagen scaffolds (1:1 and 5:1 weight ratios of nHA/collagen). Mechanical assessment demonstrated that increasing nHA incorporation correlated with increasing Young’s moduli, which could be further amplified using cross-linking treatments. Typically, the porosity of a scaffold is sacrificed to produce a stiffer material; however, through the use of nanosized particles the inclusion of up to 5:1 nHA/collagen content still preserved the high 99% porosity of the composite scaffold, allowing for maximum cell infiltration. Moreover, increasing nHA presence induced significant bioactive responses, achieving superior cellular attachment and enhanced osteogenesis, promoting earlier expression of bone markers and cell-mediated mineralization versus nHA-free collagen controls. Interestingly, these content-dependent results observed in vitro did not directly translate in vivo. Instead, similar levels of bone formation were achieved within critical-sized rat calvarial defects, independent of nHA content, following acellular implantation. The addition of nHA, both 1:1 and 5:1, induced significantly higher levels of mineralization and de novo bone ingrowth versus collagen controls as demonstrated by microcomputed tomography, histological, and histomorphometric analyses. Ultimately, these results demonstrate the immense osteoinductivity of nonaggregated nanoparticles of HA incorporated into collagen-composite scaffolds and emphasize the importance of in vivo-based evaluation of therapies intended for clinical use.
Bone regeneration requires scaffolds that possess suitable mechanical and biological properties. This study sought to develop a novel collagen-nHA biocomposite scaffold via two new methods. Firstly a ...stable nHA suspension was produced and added to a collagen slurry (suspension method), and secondly, porous collagen scaffolds were immersed in nHA suspension after freeze-drying (immersion method). Significantly stronger constructs were produced using both methods compared to collagen only scaffolds, with a high porosity maintained (>98.9%). It was found that Coll-nHA composite scaffolds produced by the suspension method were up to 18 times stiffer than the collagen control (5.50 ± 1.70 kPa vs. 0.30 ± 0.09 kPa). The suspension method was also more reproducible, and the quantity of nHA incorporated could be varied with greater ease than with the immersion technique. In addition, Coll-nHA composites display excellent biological activity, demonstrating their potential as bone graft substitutes in orthopaedic regenerative medicine.
Although local eradication is routinely attempted following introduction of disease into a new region, failure is commonplace. Epidemiological principles governing the design of successful control ...are not well-understood. We analyse factors underlying the effectiveness of reactive eradication of localised outbreaks of invading plant disease, using citrus canker in Florida as a case study, although our results are largely generic, and apply to other plant pathogens (as we show via our second case study, citrus greening). We demonstrate how to optimise control via removal of hosts surrounding detected infection (i.e. localised culling) using a spatially-explicit, stochastic epidemiological model. We show how to define optimal culling strategies that take account of stochasticity in disease spread, and how the effectiveness of disease control depends on epidemiological parameters determining pathogen infectivity, symptom emergence and spread, the initial level of infection, and the logistics and implementation of detection and control. We also consider how optimal culling strategies are conditioned on the levels of risk acceptance/aversion of decision makers, and show how to extend the analyses to account for potential larger-scale impacts of a small-scale outbreak. Control of local outbreaks by culling can be very effective, particularly when started quickly, but the optimum strategy and its performance are strongly dependent on epidemiological parameters (particularly those controlling dispersal and the extent of any cryptic infection, i.e. infectious hosts prior to symptoms), the logistics of detection and control, and the level of local and global risk that is deemed to be acceptable. A version of the model we developed to illustrate our methodology and results to an audience of stakeholders, including policy makers, regulators and growers, is available online as an interactive, user-friendly interface at http://www.webidemics.com/. This version of our model allows the complex epidemiological principles that underlie our results to be communicated to a non-specialist audience.
Alginates gel rapidly under ambient conditions and have widely documented potential to form protective matrices for sensitive bioactive cargo. Most commonly, alginate gelation occurs via calcium ...mediated electrostatic crosslinks between the linear polyuronic acid polymers. A recent breakthrough to form crosslinked alginate microcapsules (CLAMs) by in situ gelation during spray drying ("CLAMs process") has demonstrated applications in protection and controlled delivery of bioactives in food, cosmetics, and agriculture. The extent of crosslinking of alginates in CLAMs impacts the effectiveness of its barrier properties. For example, higher crosslinking extents can improve oxidative stability and limit diffusion of the encapsulated cargo. Crosslinking in CLAMs can be controlled by varying the calcium to alginate ratio; however, the choice of alginates used in the process also influences the ultimate extent of crosslinking. To understand how to select alginates to target crosslinking in CLAMs, we examined the roles of alginate molecular properties. A surprise finding was the formation of alginic acid gelling in the CLAMs that is a consequence of simultaneous and rapid pH reduction and moisture removal that occurs during spray drying. Thus, spray dried CLAMs gelation is due to calcium crosslinking and alginic acid formation, and unlike external gelation methods, is insensitive to the molecular composition of the alginates. The 'extent of gelation' of spray dried CLAMs is influenced by the molecular weights of the alginates at saturating calcium concentrations. Alginate viscosity correlates with molecular weight; thus, viscosity is a convenient criterion for selecting commercial alginates to target gelation extent in CLAMs.
Soft gamma-ray repeaters (SGRs) are a rare type of gamma-ray transient sources that are ocasionally detected as bursts in the high-energy sky. They are thought to be produced by magnetars, young ...neutron stars with very strong magnetic fields of the order of 10^(14-15) G. Only three such objects are known in our Galaxy, and a fourth one is associated with the supernova remnant N49 in the Large Magellanic Cloud. In none of these cases has an optical counterpart to either the gamma-ray flares or the quiescent source been identified. Here we present multi-wavelength observations of a puzzling source, SWIFT J195509+261406, for which we detected more than 40 flaring episodes in the optical band over a time span of 3 days, plus a faint infrared flare 11 days later, after which it returned to quiescence. We propose that SWIFT J195509+261406 is a member of a subgroup of SGRs for which the long-term X-ray emission is transient in nature. Furthermore, it is the first SGR for which bursts have been detected in the optical and near-infrared bands and maybe the link between the "persistent" SGRs and the dim isolated neutron stars.
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