-
Accounts of Chemical Research Apr 2021In spite of the importance of energetic materials to a broad range of military (munitions, missiles) and civilian (mining, space exploration) technologies, the...
In spite of the importance of energetic materials to a broad range of military (munitions, missiles) and civilian (mining, space exploration) technologies, the introduction of new chemical entities in the field occurs at a very slow pace. This situation is understandable considering the stringent requirements for cost and safety that must be met for new chemical entities to be fielded. If existing manufacturing infrastructure could be leveraged, then this would offer a fundamental shift in the discovery paradigm. Cocrystallization is an approach poised to realize this goal because it can use existing materials and make new chemical compositions through the assembly of multiple unique components in the solid state. This account describes early proof-of-principle studies with widely used energetics in the field, including 2,4,6-trinitrotoluene (TNT) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), forming cocrystals with nonenergetic coformers that alter key properties such as density, sensitivity, and morphology. The evolution of these studies to produce cocrystals between two energetic components is detailed, including those exploiting new intermolecular interaction motifs that drive assembly such as halogen bonding. Implications of cocrystallization for performance, sensitivity to external stimuli, and manufacturability are explored at each stage. The derivation of many of these cocrystals from energetic materials in common use satisfies the goal of using materials already demonstrated to be cost-effective at scale and with well-understood safety profiles. The account concludes with a discussion of cocrystallizing molecules having excess of oxidizing power with those that are oxygen-deficient to push the limits of explosive performance to unprecedented levels. The purposeful production of an arbitrary combination of two solid components into a cocrystal is far from certain, but the studies described motivate the continued exploration of novel materials and the development of predictive models for identifying crystallization partners. When such cocrystals form, many of their most important properties cannot be predicted, pointing to another challenge for the purposeful development of energetic materials based on cocrystallization.
PubMed: 33723995
DOI: 10.1021/acs.accounts.0c00830 -
BMC Veterinary Research Mar 2021Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and...
BACKGROUND
Mesenchymal stem cells (MSCs) have generated a great amount of interest in recent years as a novel therapeutic application for improving the quality of pet life and helping them free from painful conditions and diseases. It has now become critical to address the challenges related to the safety and efficacy of MSCs expanded in vitro. In this study, we establish a standardized process for manufacture of canine adipose-derived MSCs (AD-MSCs), including tissue sourcing, cell isolation and culture, cryopreservation, thawing and expansion, quality control and testing, and evaluate the safety and efficacy of those cells for clinical applications.
RESULTS
After expansion, the viability of AD-MSCs manufactured under our standardized process was above 90 %. Expression of surface markers and differentiation potential was consistent with ISCT standards. Sterility, mycoplasma, and endotoxin tests were consistently negative. AD-MSCs presented normal karyotype, and did not form in vivo tumors. No adverse events were noted in the case treated with intravenously AD-MSCs.
CONCLUSIONS
Herein we demonstrated the establishment of a feasible bioprocess for manufacturing and banking canine AD-MSCs for veterinary clinical use.
Topics: Adipose Tissue; Animals; Carcinogenicity Tests; Cell Culture Techniques; Cell Separation; Cryopreservation; Dogs; Female; Leukopenia; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice, SCID; Parvoviridae Infections; Parvovirus; Quality Control; Tissue Banks; Mice
PubMed: 33648493
DOI: 10.1186/s12917-021-02791-3 -
Bio Systems Sep 2021As shown by Hofmeyr, the processes in the living cell can be divided into three classes of efficient causes that produce each other, so making the cell closed to...
As shown by Hofmeyr, the processes in the living cell can be divided into three classes of efficient causes that produce each other, so making the cell closed to efficient causation, the hallmark of an organism. They are the enzyme catalysts of covalent metabolic chemistry, the intracellular milieu that drives the supramolecular processes of chaperone-assisted folding and self-assembly of polypeptides and nucleic acids into functional catalysts and transporters, and the membrane transporters that maintain the intracellular milieu, in particular its electrolyte composition. Each class of efficient cause can be modelled as a relational diagram in the form of a mapping in graph-theoretic form, and a minimal model of a self-manufacturing system that is closed to efficient causation can be constructed from these three mappings using the formalism of relational biology. This fabrication-assembly or (F,A)-system serves as an alternative to Robert Rosen's replicative metabolism-repair or (M,R)-system, which has been notoriously problematic to realise in terms of real biochemical processes. A key feature of the model is the explicit incorporation of formal cause, which arrests the infinite regress that plagues all relational models of the cell. The (F,A)-system is extended into a detailed relational model of the self-manufacturing cell that has a clear biochemical realisation. This (F,A) cell model allows the interpretation and visualisation of concepts such as the metabolism and repair components of Rosen's (M,R)-system, John von Neumann's universal constructor, Howard Pattee's symbol-function split via the symbol-folding transformation, Marcello Barbieri's genotype-ribotype-phenotype ontology, and Tibor Gánti's chemoton.
Topics: Animals; Cell Body; Cell Membrane; Humans; Models, Biological; Systems Biology
PubMed: 34166730
DOI: 10.1016/j.biosystems.2021.104463 -
Acta Biomaterialia Oct 2019A broad range of synthetic trabecular-like metallic lattices are 3D printed, to study the extra design freedom conferred by this new manufacturing process. The aim is to...
A broad range of synthetic trabecular-like metallic lattices are 3D printed, to study the extra design freedom conferred by this new manufacturing process. The aim is to propose new conceptual types of implant structures for superior bio-mechanical matching and osseo-integration: synthetic bone. The target designs are 3D printed in Ti-6Al-4V alloy using a laser-bed process. Systematic evaluation is then carried out: (i) their accuracy is characterised at high spatial resolution using computed X-ray tomography, to assess manufacturing robustness with respect to the original geometrical design intent and (ii) the mechanical properties - stiffness and strength - are experimentally measured, evaluated, and compared. Finally, this new knowledge is synthesised in a conceptual framework to allow the construction of so-called implant design maps, to define the processing conditions of bone tailored substitutes, with focus on spine fusion devices. The design criteria emphasise the bone stiffness-matching, preferred range of pore structure for bone in-growth, manufacturability of the device and choice of inherent materials properties which are needed for durable implants. Examples of the use of such maps are given with focus on spine fusion devices, emphasising the stiffness-matching, osseo-integration properties and choice of inherent materials properties which are needed for durable implants. STATEMENT OF SIGNIFICANCE: We present a conceptual bio-engineering design methodology for new biomedical lattices produced by additive manufacturing, which addresses some of the critical points in currently existing porous implant materials. Amongst others: (i) feasibility and accuracy of manufacturing, (ii) design to the elastic properties of bone, and (iii) sensible pores sizes for osseointegration. This has inspired new and novel geometrical latticed designs which aim at improving the properties of intervertebral fusion devices. In their fundamental form, these structures are here fabricated and tested. When integrated into medical devices, these concepts could offer superior medical outcomes.
Topics: Alloys; Bone Substitutes; Humans; Implants, Experimental; Printing, Three-Dimensional; Titanium; Tomography, X-Ray Computed
PubMed: 31394295
DOI: 10.1016/j.actbio.2019.07.049 -
Burns & Trauma 2018Material extrusion additive manufacturing has rapidly grown in use for tissue engineering research since its adoption in the year 2000. It has enabled researchers to... (Review)
Review
Material extrusion additive manufacturing has rapidly grown in use for tissue engineering research since its adoption in the year 2000. It has enabled researchers to produce scaffolds with intricate porous geometries that were not feasible with traditional manufacturing processes. Researchers can control the structural geometry through a wide range of customisable printing parameters and design choices including material, print path, temperature, and many other process parameters. Currently, the impact of these choices is not fully understood. This review focuses on how the position and orientation of extruded filaments, which sometimes referred to as the print path, lay-down pattern, or simply "scaffold design", affect scaffold properties and biological performance. By analysing trends across multiple studies, new understanding was developed on how filament position affects mechanical properties. Biological performance was also found to be affected by filament position, but a lack of consensus between studies indicates a need for further research and understanding. In most research studies, scaffold design was dictated by capabilities of additive manufacturing software rather than free-form design of structural geometry optimised for biological requirements. There is scope for much greater application of engineering innovation to additive manufacture novel geometries. To achieve this, better understanding of biological requirements is needed to enable the effective specification of ideal scaffold geometries.
PubMed: 29988731
DOI: 10.1186/s41038-018-0121-4 -
Lab on a Chip Oct 2019A scalable, generic wireless colour detector for point-of-care diagnostics in resource-limited settings is presented. The challenges faced in these settings have limited...
A scalable, generic wireless colour detector for point-of-care diagnostics in resource-limited settings is presented. The challenges faced in these settings have limited the effectiveness of point-of-care diagnostics. By combining the growing fields of paper-based diagnostics and printed electronics with Southern African clinic perspectives, a mass-producible, low-cost, paper-based solution for result readout and communication was developed. Printed radio frequency identification devices with sensing capabilities were manufactured, targeting colour detection from lateral flow test strip devices and other typical paper-based rapid test formats. The results were compared to those obtained from a commercial lateral flow test strip reader and image analysis using ImageJ, and demonstrate suitability for delivering automated readout and communication of results. The wireless colour detector is compatible with different test strip form factors, providing a modular solution and reducing the need for training. The solution is low cost and maintenance free, and thus fitting for resource-limited settings. A scalable version of the solution has been developed, making use of standard manufacturing processes for printing and packaging industries, initially using sheet-to-sheet formats, but with the goal of being scalable to roll-to-roll processes. This would enable the possibility of local manufacture, and mass distribution of the devices to those resource-limited areas where they are most needed, and where they will have the greatest impact on point-of-care testing.
Topics: Biosensing Techniques; Colorimetry; Electrochemical Techniques; Humans; Point-of-Care Testing
PubMed: 31502631
DOI: 10.1039/c9lc00552h -
International Journal of Molecular... Oct 2021The use of alloplastic materials instead of autologous cartilage grafts offers a new perspective in craniofacial reconstructive surgery. Particularly for regenerative...
The use of alloplastic materials instead of autologous cartilage grafts offers a new perspective in craniofacial reconstructive surgery. Particularly for regenerative approaches, customized implants enable the surgeon to restore the cartilaginous framework of the ear without donor site morbidity. However, high development and production costs of commercially available implants impede clinical translation. For this reason, the usability of a low-cost 3D printer (Ultimaker 2+) as an inhouse-production tool for cheap surgical implants was investigated. The open software architecture of the 3D printer was modified in order to enable printing of biocompatible and biologically degradable polycaprolactone (PCL). Firstly, the printing accuracy and limitations of a PCL implant were compared to reference materials acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA). Then the self-made PCL-scaffold was seeded with adipose-tissue derived stem cells (ASCs), and biocompatibility was compared to a commercially available PCL-scaffold using a cell viability staining (FDA/PI) and a dsDNA quantification assay (PicoGreen). Secondly, porous and solid patient-customized ear constructs were manufactured from mirrored CT-imagining data using a computer-assisted design (CAD) and computer-assisted manufacturing (CAM) approach to evaluate printing accuracy and reproducibility. The results show that printing of a porous PCL scaffolds was possible, with an accuracy equivalent to the reference materials at an edge length of 10 mm and a pore size of 0.67 mm. Cell viability, adhesion, and proliferation of the ASCs were equivalent on self-made and the commercially available PCL-scaffolds. Patient-customized ear constructs could be produced well in solid form and with limited accuracy in porous form from all three thermoplastic materials. Printing dimensions and quality of the modified low-cost 3D printer are sufficient for selected tissue engineering applications, and the manufacturing of personalized ear models for surgical simulation at manufacturing costs of EUR 0.04 per cell culture scaffold and EUR 0.90 (0.56) per solid (porous) ear construct made from PCL. Therefore, in-house production of PCL-based tissue engineering scaffolds and surgical implants should be further investigated to facilitate the use of new materials and 3D printing in daily clinical routine.
Topics: Computer-Aided Design; Ear Auricle; Humans; Polyesters; Printing, Three-Dimensional; Tissue Scaffolds
PubMed: 34769096
DOI: 10.3390/ijms222111667 -
Molecular Therapy. Methods & Clinical... Dec 2023Base editing is a revolutionary gene-editing technique enabling the introduction of point mutations into the genome without generating detrimental DNA double-stranded...
Base editing is a revolutionary gene-editing technique enabling the introduction of point mutations into the genome without generating detrimental DNA double-stranded breaks. Base-editing enzymes are commonly delivered in the form of modified linear messenger RNA (mRNA) that is costly to produce. Here, we address this problem by developing a simple protocol for manufacturing base-edited cells using circular RNA (circRNA), which is less expensive to synthesize. Compared with linear mRNA, higher editing efficiencies were achieved with circRNA, enabling an 8-fold reduction in the amount of RNA required. We used this protocol to manufacture a clinical dose (1 × 10 cells) of base-edited chimeric antigen receptor (CAR) T cells lacking expression of the inhibitory receptor, PD-1. Editing efficiencies of up to 86% were obtained using 0.25 μg circRNA/1 × 10 cells. Increased editing efficiencies with circRNA were attributed to more efficient translation. These results suggest that circRNA, which is less expensive to produce than linear mRNA, is a viable option for reducing the cost of manufacturing base-edited cells at scale.
PubMed: 37886606
DOI: 10.1016/j.omtm.2023.101123 -
International Journal of Environmental... Nov 2018More and more countries employ the Carbon Cap and Trade mechanism (CCT-mechanism) to stimulate the manufacturer to produce much more eco-friendly products. In this...
More and more countries employ the Carbon Cap and Trade mechanism (CCT-mechanism) to stimulate the manufacturer to produce much more eco-friendly products. In this paper, we study how the CCT-mechanism affects competitive manufacturers' product design and pricing strategies. Assume that there are two competitive manufacturers; we give the optimal closed form solutions of the carbon emission reduction rates and retail prices in the Nash game model and the Stackelberg game model with CCT-mechanism, respectively. Additionally, we also discuss the impacts of CCT-mechanism, consumer environmental awareness (CEA), and the sensitivity of switchovers toward price on the optimal carbon emission reduction rates, retail prices, and manufacturers' profits. We find that (i) when the carbon quota is not enough, there is a trade off between investing in producing much greener product and purchasing carbon quota; when the carbon price is not high, the manufacturer tends to purchase the carbon quota; and when the carbon price is much higher, the manufacturer is more willing to increase the environmental quality of the product; (ii) manufacturer's size affects product's emission reduction rate and manufacturer's optimal profit; larger manufacturer tends to produce much greener product, but it does not mean that he could obtain much more money than the small manufacturer; and (iii) the decision sequence changes manufacturer's strategies; the optimal emission reduction rate in Nash and Stackelberg game models are almost the same, but the differences of prices and profits between Nash and Stackelberg model's are much bigger.
Topics: Carbon; Consumer Behavior; Costs and Cost Analysis; Decision Making; Economic Competition
PubMed: 30453588
DOI: 10.3390/ijerph15112570