Osteochondral Tissue Engineering: The Potential of Electrospinning and Additive Manufacturing

The socioeconomic impact of osteochondral (OC) damage has been increasing steadily over time in the global population, and the promise of tissue engineering in generating biomimetic tissues replicating the physiological OC environment and architecture has been falling short of its projected potential. The most recent advances in OC tissue engineering are summarised in this work, with a focus on electrospun and 3D printed biomaterials combined with stem cells and biochemical stimuli, to identify what is causing this pitfall between the bench and the patients' bedside. Even though significant progress has been achieved in electrospinning, 3D-(bio)printing, and induced pluripotent stem cell (iPSC) technologies, it is still challenging to artificially emulate the OC interface and achieve complete regeneration of bone and cartilage tissues. Their intricate architecture and the need for tight spatiotemporal control of cellular and biochemical cues hinder the attainment of long-term functional integration of tissue-engineered constructs. Moreover, this complexity and the high variability in experimental conditions used in different studies undermine the scalability and reproducibility of prospective regenerative medicine solutions. It is clear that further development of standardised, integrative, and economically viable methods regarding scaffold production, cell selection, and additional biochemical and biomechanical stimulation is likely to be the key to accelerate the clinical translation and fill the gap in OC treatment

An investigation of alkaline phosphatase enzymatic activity after electrospinning and electrospraying

The high target specificity and multifunctionality of proteins has led to great interest in their clinical use. To this end, the development of delivery systems capable of preserving their bioactivity and improving bioavailability is pivotal to achieve high effectiveness and satisfactory therapeutic outcomes. Electrohydrodynamic (EHD) techniques, namely electrospinning and electrospraying, have been widely explored for protein encapsulation and delivery. In this work, monoaxial and coaxial electrospinning and electrospraying were used to encapsulate alkaline phosphatase (ALP) into poly(ethylene oxide) fibres and particles, respectively, and the effects of the processing techniques on the integrity and bioactivity of the enzyme were assessed. A full morphological and physicochemical characterisation of the blend and core-shell products was performed. ALP was successfully encapsulated within monolithic and core-shell electrospun fibres and electrosprayed particles, with drug loadings and encapsulation efficiencies of up to 21% and 99%, respectively. Monoaxial and coaxial electrospinning were equally effective in preserving ALP function, leading to no activity loss compared to fresh aqueous solutions of the enzyme. While the same result was observed for monoaxial electrospraying, coaxial electrospraying of ALP caused a 40% reduction in its bioactivity, which was attributed to the high voltage (22.5 kV) used during processing. This demonstrates that choosing between blend and coaxial EHD processing for protein encapsulation is not always straightforward, being highly dependent on the chosen therapeutic agent and the effects of the processing conditions on bioactivity

Protein encapsulation by electrospinning and electrospraying

Given the increasing interest in the use of peptide- and protein-based agents in therapeutic strategies, it is fundamental to develop delivery systems capable of preserving the biological activity of these molecules upon administration, and which can provide tuneable release profiles. Electrohydrodynamic (EHD) techniques, encompassing electrospinning and electrospraying, allow the generation of fibres and particles with high surface area-to-volume ratios, versatile architectures, and highly controllable release profiles. This review is focused on exploring the potential of different EHD methods (including blend, emulsion, and co−/multi-axial electrospinning and electrospraying) for the development of peptide and protein delivery systems. An overview of the principles of each technique is first presented, followed by a survey of the literature on the encapsulation of enzymes, growth factors, antibodies, hormones, and vaccine antigens using EHD approaches. The possibility for localised delivery using stimuli-responsive systems is also explored. Finally, the advantages and challenges with each EHD method are summarised, and the necessary steps for clinical translation and scaled-up production of electrospun and electrosprayed protein delivery systems are discussed

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Synergies for Improving Oil Palm Production and Forest Conservation in Floodplain Landscapes

Lowland tropical forests are increasingly threatened with conversion to oil palm as global demand and high profit drives crop expansion throughout the world’s tropical regions. Yet, landscapes are not homogeneous and regional constraints dictate land suitability for this crop. We conducted a regional study to investigate spatial and economic components of forest conversion to oil palm within a tropical floodplain in the Lower Kinabatangan, Sabah, Malaysian Borneo. The Kinabatangan ecosystem harbours significant biodiversity with globally threatened species but has suffered forest loss and fragmentation. We mapped the oil palm and forested landscapes (using object-based-image analysis, classification and regression tree analysis and on-screen digitising of high-resolution imagery) and undertook economic modelling. Within the study region (520,269 ha), 250,617 ha is cultivated with oil palm with 77% having high Net-Present-Value (NPV) estimates ($413/ha?yr–$637/ha?yr); but 20.5% is under-producing. In fact 6.3% (15,810 ha) of oil palm is commercially redundant (with negative NPV of $-299/ha?yr-$-65/ha?yr) due to palm mortality from flood inundation. These areas would have been important riparian or flooded forest types. Moreover, 30,173 ha of unprotected forest remain and despite its value for connectivity and biodiversity 64% is allocated for future oil palm. However, we estimate that at minimum 54% of these forests are unsuitable for this crop due to inundation events. If conversion to oil palm occurs, we predict a further 16,207 ha will become commercially redundant. This means that over 32,000 ha of forest within the floodplain would have been converted for little or no financial gain yet with significant cost to the ecosystem. Our findings have globally relevant implications for similar floodplain landscapes undergoing forest transformation to agriculture such as oil palm. Understanding landscape level constraints to this crop, and transferring these into policy and practice, may provide conservation and economic opportunities within these seemingly high opportunity cost landscapes

Abnormal NK cell lymphocytosis detected after splenectomy: association with repeated infections, relapsing neutropenia, and persistent polyclonal B-cell proliferation

Abnormal NK cell lymphocytosis detected after splenectomy: association with repeated infections, relapsing neutropenia, and persistent polyclonal B-cell proliferation. Granjo E, Lima M, Fraga M, Santos F, Magalhães C, Queirós ML, Moreira I, Rocha S, Silva AS, Rebelo I, Quintanilha A, Ribeiro ML, Candeias J, Orfão A. Department of Hematology, Hospital S. João, Porto, Portugal. [email protected] Abstract We report the case of a boy with hereditary spherocytosis who presented with mild microcytic hypochromic anemia and recurrent leg ulcers that had been present since childhood. Chronic natural killer (NK) cell and B-cell lymphocytosis was detected 1 year after therapeutic splenectomy during investigation of recurrent episodes of neutropenia and persistent lymphocytosis. NK cells proved to be abnormal at immunophenotyping studies, and B-cells were polyclonal and displayed a normal immunophenotype. Genotypic analysis of T-cell receptor (TCR)-beta and TCR-gamma genes showed a germ-line pattern. The clinical course of this patient was characterized by multiple pulmonary infections and amygdalitis. We discuss the potential roles of persistent immune stimulation due to chronic hemolysis and severe leg ulcers and of splenectomy in the origin of NK cell lymphocytosis and the relationship between NK cells and recurrent infections, relapsing neutropenia, and polyclonal B-cell response

The role of climate, marine influence and sedimentation rates in late-Holocene estuarine evolution (SW Portugal)

Estuaries are sensitive to changes in global to regional sea level, to climate-driven variation in rainfall and to fluvial discharge. In this study, we use source and environmentally sensitive proxies together with radiocarbon dating to examine a 7-m-thick sedimentary record from the Sado estuary accumulated throughout the last 3.6 kyr. The lithofacies, geochemistry and diatom assemblages in the sediments accumulated between 3570 and 3240 cal. BP indicate a mixture between terrestrial and marine sources. The relative contribution of each source varied through time as sedimentation progressed in a low intertidal to high subtidal and low-energy accreting tidal flat. The sedimentation proceeded under a general pattern of drier and higher aridity conditions, punctuated by century-long changes of the rainfall regime that mirror an increase in storminess that affected SW Portugal and Europe. The sediment sequence contains evidence of two periods characterized by downstream displacement of the estuarine/freshwater transitional boundary, dated to 3570-3400 cal. BP and 3300-3240 cal. BP. These are intercalated by one episode where marine influence shifted upstream. All sedimentation episodes developed under high terrestrial sediment delivery to this transitional region, leading to exceptionally high sedimentation rates, independently of the relative expression of terrestrial/marine influences in sediment facies. Our data show that these disturbances are mainly climate-driven and related to variations in rainfall and only secondarily with regional sea-level oscillations. From 3240 cal. BP onwards, an abrupt change in sediment facies is noted, in which the silting estuarine bottom reaches mean sea level and continued accreting until present under prevailing freshwater conditions, the tidal flat changing to an alluvial plain. The environmental modification is accompanied by a pronounced change in sedimentation rate that decreased by two orders of magnitude, reflecting the loss of accommodation space rather than the influence of climate or regional sea-level drivers.FCT by Spanish Ministry of Science and Innovation [SFRH/BD/110270/2015, HAR2014-51830-P, HAR2011-29907-C03-00]FCTPortuguese Foundation for Science and Technology [PTDC/HISARQ/121592/2010]Instituto Dom Luiz-IDL [UID/GEO/50019/2013]info:eu-repo/semantics/publishedVersio

Changes in grassland management and linear infrastructures associated to the decline of an endangered bird population

European grassland birds are experiencing major population declines, mainly due to changes in farmland management. We analyzed the role of habitat availability, grazing management and linear infrastructures (roads and power lines) in explaining spatial and temporal variation in the population density of little bustards (Tetrax tetrax) in Portugal, during a decade in which the species population size halved. We used data from 51 areas (totaling ca. 1,50,000 ha) that were sampled in two different periods (2003–2006 and 2016). In 2003–2006, when the species occurred at high densities, habitat availability was the only factor affecting spatial variation in bustard density. In the 2016 survey, variation in density was explained by habitat availability and livestock management, with reduced bird numbers in areas with higher proportions of cattle. Population declines across the study period were steeper in areas that initially held higher densities of bustards and in areas with a higher proportion of cattle in the total stocking rate. Areas with higher densities of power lines also registered greater density declines, probably due to avoidance behavior and to increased mortality. Overall, our results show little bustards are currently lacking high quality grassland habitat, whose persistence depends on extensive grazing regimes and low linear infrastructure densitiesinfo:eu-repo/semantics/publishedVersio