Modal analysis of novel coronavirus (SARS COV-2) using finite element methodology.

Many new engineering and scientific innovations have been proposed to date to passivate the novel coronavirus (SARS CoV-2), with the aim of curing the related disease that is now recognised as COVID-19. Currently, vaccine development remains the most reliable solution available. Efforts to provide solutions as alternatives to vaccinations are growing and include established control of behaviours such as self-isolation, social distancing, employing facial masks and use of antimicrobial surfaces. The work here proposes a novel engineering method employing the concept of resonant frequencies to denature SARS CoV-2. Specifically, "modal analysis" is used to computationally analyse the Eigenvalues and Eigenvectors i.e. frequencies and mode shapes to denature COVID-19. An average virion dimension of 63 nm with spike proteins number 6, 7 and 8 were examined, which revealed a natural frequency of a single virus in the range of 88-125 MHz. The information derived about the natural frequency of the virus through this study will open newer ways to exploit medical solutions to combat future pandemics.

Biomimetic generation of the strongest known biomaterial found in limpet tooth.

The biomaterial with the highest known tensile strength is a unique composite of chitin and goethite (α-FeO(OH)) present in teeth from the Common Limpet (Patella vulgata). A biomimetic based on limpet tooth, with corresponding high-performance mechanical properties is highly desirable. Here we report on the replication of limpet tooth developmental processes ex vivo, where isolated limpet tissue and cells in culture generate new biomimetic structures. Transcriptomic analysis of each developmental stage of the radula, the organ from which limpet teeth originate, identifies sequential changes in expression of genes related to chitin and iron processing. We quantify iron and chitin metabolic processes in the radula and grow isolated radula cells in vitro. Bioinspired material can be developed with electrospun chitin mineralised by conditioned media from cultured radula cells. Our results inform molecular processes behind the generation of limpet tooth and establish a platform for development of a novel biomimetic with comparable properties.

Resilient and agile engineering solutions to address societal challenges such as coronavirus pandemic.

The world is witnessing tumultuous times as major economic powers including the US, UK, Russia, India, and most of Europe continue to be in a state of lockdown. The worst-hit sectors due to this lockdown are sales, production (manufacturing), transport (aerospace and automotive) and tourism. Lockdowns became necessary as a preventive measure to avoid the spread of the contagious and infectious "Coronavirus Disease 2019" (COVID-19). This newly identified disease is caused by a new strain of the virus being referred to as Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS CoV-2; formerly called 2019-nCoV). We review the current medical and manufacturing response to COVID-19, including advances in instrumentation, sensing, use of lasers, fumigation chambers and development of novel tools such as lab-on-the-chip using combinatorial additive and subtractive manufacturing techniques and use of molecular modelling and molecular docking in drug and vaccine discovery. We also offer perspectives on future considerations on climate change, outsourced versus indigenous manufacturing, automation, and antimicrobial resistance. Overall, this paper attempts to identify key areas where manufacturing can be employed to address societal challenges such as COVID-19.

Evaluation of X-ray tomography contrast agents: A review of production, protocols, and biological applications.

X-ray computed tomography is a strong tool that finds many applications both in medical applications and in the investigation of biological and nonbiological samples. In the clinics, X-ray tomography is widely used for diagnostic purposes whose three-dimensional imaging in high resolution helps physicians to obtain detailed image of investigated regions. Researchers in biological sciences and engineering use X-ray tomography because it is a nondestructive method to assess the structure of their samples. In both medical and biological applications, visualization of soft tissues and structures requires special treatment, in which special contrast agents are used. In this detailed report, molecule-based and nanoparticle-based contrast agents used in biological applications to enhance the image quality were compiled and reported. Special contrast agent applications and protocols to enhance the contrast for the biological applications and works to develop nanoparticle contrast agents to enhance the contrast for targeted drug delivery and general imaging applications were also assessed and listed.

Full-Field Strain Analysis of Bone-Biomaterial Systems Produced by the Implantation of Osteoregenerative Biomaterials in an Ovine Model.

Osteoregenerative biomaterials for the treatment of bone defects are under much development, with the aim of favoring osteointegration up to complete bone regeneration. A detailed investigation of bone-biomaterial integration is vital to understand and predict the ability of such materials to promote bone formation, preventing further bone damage and supporting load-bearing regions. This study aims to characterize the ex vivo micromechanics and microdamage evolution of bone-biomaterial systems at the tissue level, combining high-resolution synchrotron microcomputed tomography, in situ mechanics and digital volume correlation. Results showed that the main microfailure events were localized close to or within the newly formed bone tissue, in proximity to the bone-biomaterial interface. The apparent nominal compressive load applied to the composite structures resulted in a complex loading scenario, mainly due to the higher heterogeneity but also to the different biomaterial degradation mechanisms. The full-field strain distribution allowed characterization of microdamage initiation and progression. The findings reported in this study provide a deeper insight into bone-biomaterial integration and micromechanics in relation to the osteoregeneration achieved in vivo for a variety of biomaterials. This could ultimately be used to improve bone tissue regeneration strategies.

Pore shape and size dependence on cell growth into electrospun fiber scaffolds for tissue engineering: 2D and 3D analyses using SEM and FIB-SEM tomography.

Electrospun nanofibers have ability to boost cell proliferation in tissue engineered scaffolds as their structure remind cells extra cellular matrix of the native tissue. The complex architecture and network of nanofibrous scaffolds requires advanced characterization methods to understand interrelationship between cells and nanofibers. In our study, we used complementary 2D and 3D analyses of electrospun polylactide-co-glycolide acid (PLGA) scaffolds in two configurations: aligned and randomly oriented nanofibers. Sizes of pores and fibers, pores shapes and porosity, before and after cell culture, were verified by imaging with scanning electron microscopy (SEM) and combination of focus ion beam (FIB) and SEM to obtain 3D reconstructions of samples. Using FIB-SEM tomography for 3D reconstructions and 2D analyses, a unique set of data allowing understanding cell proliferation mechanism into the electrospun scaffolds, was delivered. Critically, the proliferation of cells into nanofibers network depends mainly on the pore shape and pores interconnections, which allow deep integration between cells and nanofibers. The proliferation of cells inside the network of fibers is much limited for aligned fibers comparing to randomly oriented fibers. For random fibers cells have easier way to integrate inside the scaffold as the circularity of pores and their sizes are larger than for aligned scaffolds. The complex architecture of electrospun scaffolds requires appropriate, for tissue engineering needs, cell seeding and culture methods, to maximize tissue growth in vitro environment.

Preservation of Bone Tissue Integrity with Temperature Control for In Situ SR-MicroCT Experiments.

Digital volume correlation (DVC), combined with in situ synchrotron microcomputed tomography (SR-microCT) mechanics, allows for 3D full-field strain measurement in bone at the tissue level. However, long exposures to SR radiation are known to induce bone damage, and reliable experimental protocols able to preserve tissue properties are still lacking. This study aims to propose a proof-of-concept methodology to retain bone tissue integrity, based on residual strain determination using DVC, by decreasing the environmental temperature during in situ SR-microCT testing. Compact and trabecular bone specimens underwent five consecutive full tomographic data collections either at room temperature or 0 °C. Lowering the temperature seemed to reduce microdamage in trabecular bone but had minimal effect on compact bone. A consistent temperature gradient was measured at each exposure period, and its prolonged effect over time may induce localised collagen denaturation and subsequent damage. DVC provided useful information on irradiation-induced microcrack initiation and propagation. Future work is necessary to apply these findings to in situ SR-microCT mechanical tests, and to establish protocols aiming to minimise the SR irradiation-induced damage of bone.

Effect of SR-microCT radiation on the mechanical integrity of trabecular bone using in situ mechanical testing and digital volume correlation.

The use of synchrotron radiation micro-computed tomography (SR-microCT) is becoming increasingly popular for studying the relationship between microstructure and bone mechanics subjected to in situ mechanical testing. However, it is well known that the effect of SR X-ray radiation can considerably alter the mechanical properties of bone tissue. Digital volume correlation (DVC) has been extensively used to compute full-field strain distributions in bone specimens subjected to step-wise mechanical loading, but tissue damage from sequential SR-microCT scans has not been previously addressed. Therefore, the aim of this study is to examine the influence of SR irradiation-induced microdamage on the apparent elastic properties of trabecular bone using DVC applied to in situ SR-microCT tomograms obtained with different exposure times. Results showed how DVC was able to identify high local strain levels (> 10,000 µÎµ) corresponding to visible microcracks at high irradiation doses (~ 230 kGy), despite the apparent elastic properties remained unaltered. Microcracks were not detected and bone plasticity was preserved for low irradiation doses (~ 33 kGy), although image quality and consequently, DVC performance were reduced. DVC results suggested some local deterioration of tissue that might have resulted from mechanical strain concentration further enhanced by some level of local irradiation even for low accumulated dose.

Hydration dependent mechanical performance of denture adhesive hydrogels.

OBJECTIVE: Hydration in denture adhesives regulates the formation of complex morphologies and mechanical function. Multiscale experimental approaches are required to evaluate the impact of hydration on the inherent heterogeneity of denture adhesive-based hydrogels at different length scales and the impact of such phenomena on adhesion performance. METHODS: The morphology of hydrated denture adhesives was examined via cryo-scanning electron microscopy (cryo-SEM). The rheological and thermodynamic behaviour of bulk hydrated deture adhesives was examined by rheology and differential scanning Calorimetry (DSC). The microscopic mechanical properties of the denture adhesives were characterised by atomic force microscopy (AFM) and compared to the properties measured at the macroscopic scale. RESULTS: The rheological and mechanical properties of commerically available denture adhesive hydrogels were found to be critically dependent on both the formulation of the adhesives and their hydration level. Clear progression of phase separation was observed in hydrated denture adhesives as hydration increased and changed the mechanical properties of the adhesives at multiple length scales. The adhesives displaying more heterogeneous structures, which were associated with the presence of hydrophobic and organic compounds in the formulation, exhibited more variable mechanical behaviour and weaker rheological properties, but stronger adhesive properties. SIGNIFICANCE: Our results are important in defining the relationships between hydrophilicity, hydration, mechanical and adhesive properties of denture adhesives, allowing the development of improved chemical formulations that control the fixation of dentures.

X-ray Imaging of Transplanar Liquid Transport Mechanisms in Single Layer Textiles.

Understanding the penetration of liquids within textile fibers is critical for the development of next-generation smart textiles. Despite substantial research on liquid penetration in the plane of the textile, little is known about how the liquid penetrates in the thickness direction. Here we report a time-resolved high-resolution X-ray measurement of the motion of the liquid-air interface within a single layer textile, as the liquid is transported across the textile thickness following the deposition of a droplet. The measurement of the time-dependent position of the liquid meniscus is made possible by the use of ultrahigh viscosity liquids (dynamic viscosity from 105 to 2.5 × 106 times larger than water). This approach enables imaging due to the slow penetration kinetics. Imaging results suggest a three-stage penetration process with each stage being associated with one of the three types of capillary channels existing in the textile geometry, providing insights into the effect of the textile structure on the path of the three-dimensional liquid meniscus. One dimensional kinetics studies show that our data for the transplanar penetration depth ΔxL vs time do not conform to a power law, and that the measured rate of penetration for long times is smaller than that predicted by Lucas-Washburn kinetics, challenging commonly held assumptions regarding the validity of power laws when applied to relatively thin textiles.

Micro-mechanical properties of the tendon-to-bone attachment.

The tendon-to-bone attachment (enthesis) is a complex hierarchical tissue that connects stiff bone to compliant tendon. The attachment site at the micrometer scale exhibits gradients in mineral content and collagen orientation, which likely act to minimize stress concentrations. The physiological micromechanics of the attachment thus define resultant performance, but difficulties in sample preparation and mechanical testing at this scale have restricted understanding of structure-mechanical function. Here, microscale beams from entheses of wild type mice and mice with mineral defects were prepared using cryo-focused ion beam milling and pulled to failure using a modified atomic force microscopy system. Micromechanical behavior of tendon-to-bone structures, including elastic modulus, strength, resilience, and toughness, were obtained. Results demonstrated considerably higher mechanical performance at the micrometer length scale compared to the millimeter tissue length scale, describing enthesis material properties without the influence of higher order structural effects such as defects. Micromechanical investigation revealed a decrease in strength in entheses with mineral defects. To further examine structure-mechanical function relationships, local deformation behavior along the tendon-to-bone attachment was determined using local image correlation. A high compliance zone near the mineralized gradient of the attachment was clearly identified and highlighted the lack of correlation between mineral distribution and strain on the low-mineral end of the attachment. This compliant region is proposed to act as an energy absorbing component, limiting catastrophic failure within the tendon-to-bone attachment through higher local deformation. This understanding of tendon-to-bone micromechanics demonstrates the critical role of micrometer scale features in the mechanics of the tissue. STATEMENT OF SIGNIFICANCE: The tendon-to-bone attachment (enthesis) is a complex hierarchical tissue with features at a numerous scales that dissipate stress concentrations between compliant tendon and stiff bone. At the micrometer scale, the enthesis exhibits gradients in collagen and mineral composition and organization. However, the physiological mechanics of the enthesis at this scale remained unknown due to difficulty in preparing and testing micrometer scale samples. This study is the first to measure the tensile mechanical properties of the enthesis at the micrometer scale. Results demonstrated considerably enhanced mechanical performance at the micrometer length scale compared to the millimeter tissue length scale and identified a high-compliance zone near the mineralized gradient of the attachment. This understanding of tendon-to-bone micromechanics demonstrates the critical role of micrometer scale features in the mechanics of the tissue.

Failure mechanisms in denture adhesives.

OBJECTIVE: The mechanical properties of bio adhesives in oral care application are expected to be critical in defining the stability and release of devices such as dentures from the oral tissue. A multiscale experimental mechanical approach is used to evaluate the performance of denture adhesive materials. METHODS: The inherent mechanical behavior of denture fixatives was examined by separating adhesive material from a representative polymethyl methacrylate (PMMA) surface using atomic force microscopy (AFM) approaches and compared to macroscopic mechanical testing. RESULTS: Failure of denture adhesive material was found to be critically dependent on the formation of fibrillar structures within the adhesive. Small scale mechanical testing provided evidence for the mechanical properties of the fibrillar structures formed within the adhesive in macroscopic mechanical testing and indicated the importance of the forces required to fail the adhesive at these small length scales in controlling both the maximum forces sustained by the bulk material as well as the ease of separating the adhesive from PMMA surfaces. SIGNIFICANCE: Our results are important in defining the performance of denture fixative materials and their control of adhesive behavior, allowing the potential to tune properties required in the adhesion and removal of dentures.

Type VI Collagen Regulates Dermal Matrix Assembly and Fibroblast Motility.

Type VI collagen is a nonfibrillar collagen expressed in many connective tissues and implicated in extracellular matrix (ECM) organization. We hypothesized that type VI collagen regulates matrix assembly and cell function within the dermis of the skin. In the present study we examined the expression pattern of type VI collagen in normal and wounded skin and investigated its specific function in new matrix deposition by human dermal fibroblasts. Type VI collagen was expressed throughout the dermis of intact human skin, at the expanding margins of human keloid samples, and in the granulation tissue of newly deposited ECM in a mouse model of wound healing. Generation of cell-derived matrices (CDMs) by human dermal fibroblasts with stable knockdown of COL6A1 revealed that type VI collagen-deficient matrices were significantly thinner and contained more aligned, thicker, and widely spaced fibers than CDMs produced by normal fibroblasts. In addition, there was significantly less total collagen and sulfated proteoglycans present in the type VI collagen-depleted matrices. Normal fibroblasts cultured on de-cellularized CDMs lacking type VI collagen displayed increased cell spreading, migration speed, and persistence. Taken together, these findings indicate that type VI collagen is a key regulator of dermal matrix assembly, composition, and fibroblast behavior and may play an important role in wound healing and tissue regeneration.

Evaluation of bioprosthetic heart valve failure using a matrix-fibril shear stress transfer approach.

A matrix-fibril shear stress transfer approach is devised and developed in this paper to analyse the primary biomechanical factors which initiate the structural degeneration of the bioprosthetic heart valves (BHVs). Using this approach, the critical length of the collagen fibrils l c and the interface shear acting on the fibrils in both BHV and natural aortic valve (AV) tissues under physiological loading conditions are calculated and presented. It is shown that the required critical fibril length to provide effective reinforcement to the natural AV and the BHV tissue is l c  = 25.36 µm and l c  = 66.81 µm, respectively. Furthermore, the magnitude of the required shear force acting on fibril interface to break a cross-linked fibril in the BHV tissue is shown to be 38 µN, while the required interfacial force to break the bonds between the fibril and the surrounding extracellular matrix is 31 µN. Direct correlations are underpinned between these values and the ultimate failure strength and the failure mode of the BHV tissue compared with the natural AV, and are verified against the existing experimental data. The analyses presented in this paper explain the role of fibril interface shear and critical length in regulating the biomechanics of the structural failure of the BHVs, for the first time. This insight facilitates further understanding into the underlying causes of the structural degeneration of the BHVs in vivo.

3D nanomechanical evaluations of dermal structures in skin.

Skin is a multilayered multiscale composite material with a range of mechanical and biochemical functions. The mechanical properties of dermis are important to understand in order to improve and compare on-going in vitro experiments to physiological conditions, especially as the mechanical properties of the dermis can play a crucial role in determining cell behaviour. Spatial and isotropy variations in dermal mechanics are thus critical in such understanding of complex skin structures. Atomic force microscopy (AFM) based indentation was used in this study to quantify the three dimensional mechanical properties of skin at nanoscale resolution over micrometre length scales. A range of preparation methods was examined and a mechanically non-evasive freeze sectioning followed by thawing method was found to be suitable for the AFM studies. Subsequent mechanical evaluations established macroscale isotropy of the dermis with the ground substance of the dermis dominating the mechanical response. Mechanical analysis was extended to show significant variation in the elastic modulus of the dermis between anatomical locations that suggest changes in the physiological environment influence local mechanical properties. Our results highlight dependence between an isotropic mechanical response of the dermal microenvironment at the nanoscale and anatomical location that define the variable mechanical behaviour of the dermis.

Microscopy and supporting data for osteoblast integration within an electrospun fibrous network.

This data article contains data related to the research article entitled "3D imaging of cell interactions with electrospun PLGA nanofiber membranes for bone regeneration" by Stachewicz et al. [1]. In this paper we include additional data showing degradation analysis of poly(d,l-lactide-co-glycolide acid) (PLGA) electrospun fibers in medium and air using fiber diameter distribution histograms. We also describe the steps used in "slice and view" tomography techniques with focused ion beam (FIB) microscopy and scanning electron microscopy (SEM) and detail the image analysis to obtain 3D reconstruction of osteoblast cell integration with electrospun network of fibers. Further supporting data and detailed information on the quantification of cell growth within the electrospun nanofiber membranes is provided.

The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes.

The transmission of mechanical forces to the nucleus is important for intracellular positioning, mitosis and cell motility, yet the contribution of specific components of the cytoskeleton to nuclear mechanotransduction remains unclear. In this study, we examine how crosstalk between the cytolinker plectin and F-actin controls keratin network organisation and the 3D nuclear morphology of keratinocytes. Using micro-patterned surfaces to precisely manipulate cell shape, we find that cell adhesion and spreading regulate the size and shape of the nucleus. Disruption of the keratin cytoskeleton through loss of plectin facilitated greater nuclear deformation, which depended on acto-myosin contractility. Nuclear morphology did not depend on direct linkage of the keratin cytoskeleton with the nuclear membrane, rather loss of plectin reduced keratin filament density around the nucleus. We further demonstrate that keratinocytes have abnormal nuclear morphologies in the epidermis of plectin-deficient, epidermolysis bullosa simplex patients. Taken together, our data demonstrate that plectin is an essential regulator of nuclear morphology in vitro and in vivo and protects the nucleus from mechanical deformation.

3D imaging of cell interactions with electrospun PLGA nanofiber membranes for bone regeneration.

The interaction between resident cells and electrospun nanofibers is critical in determining resultant osteoblast proliferation and activity in orthopedic tissue scaffolds. The use of techniques to evaluate cell-nanofiber interactions is critical in understanding scaffold function, with visualization promising unparalleled access to spatial information on such interactions. 3D tomography exploiting focused ion beam (FIB)-scanning electron microscopy (SEM) was used to examine electrospun nanofiber scaffolds to understand the features responsible for (osteoblast-like MC3T3-E1 and UMR106) cell behavior and resultant scaffold function. 3D imaging of cell-nanofiber interactions within a range of electrospun poly(d,l-lactide-co-glycolide acid) (PLGA) nanofiber scaffold architectures indicated a coherent interface between osteoblasts and nanofiber surfaces, promoting osteoblast filopodia formation for successful cell growth. Coherent cell-nanofiber interfaces were demonstrated throughout a randomly organized and aligned nanofiber network. Gene expression of UMR106 cells grown on PLGA fibers did not deviate significantly from those grown on plastic, suggesting maintenance of phenotype. However, considerably lower expression of Ibsp and Alpl on PLGA fibers might indicate that these cells are still in the proliferative phase compared with a more differentiated cell on plastic. This work demonstrates the synergy between designing electrospun tissue scaffolds and providing comprehensive evaluation through high resolution imaging of resultant 3-dimensional cell growth within the scaffold. STATEMENT OF SIGNIFICANCE: Membranes made from electrospun nanofibers are potentially excellent for promoting bone growth for next-generation tissue scaffolds. The effectiveness of an electrospun membrane is shown here using high resolution 3D imaging to visualize the interaction between cells and the nanofibers within the membrane. Nanofibers that are aligned in one direction control cell growth at the surface of the membrane whereas random nanofibers cause cell growth into the membrane. Such observations are important and indicate that lateral cell growth at the membrane surface using aligned nanofibers could be used for rapid tissue repair whereas slower but more extensive tissue production is promoted by membranes containing random nanofibers.

Wetting Hierarchy in Oleophobic 3D Electrospun Nanofiber Networks.

Wetting behavior between electrospun nanofibrous networks and liquids is of critical importance in many applications including filtration and liquid-repellent textiles. The relationship between intrinsic nanofiber properties, including surface characteristics, and extrinsic nanofibrous network organization on resultant wetting characteristics of the nanofiber network is shown in this work. Novel 3D imaging exploiting focused ion beam (FIB) microscopy and cryo-scanning electron microscopy (cryo-SEM) highlights a wetting hierarchy that defines liquid interactions with the network. Specifically, small length scale partial wetting between individual electrospun nanofibers and low surface tension liquids, measured both using direct SEM visualization and a nano Wilhelmy balance approach, provides oleophobic surfaces due to the high porosity of electrospun nanofiber networks. These observations conform to a metastable Cassie-Baxter regime and are important in defining general rules for understanding the wetting behavior between fibrous solids and low surface tension liquids for omniphobic functionality.

Structural orientation dependent sub-lamellar bone mechanics.

The lamellar unit is a critical component in defining the overall mechanical properties of bone. In this paper, micro-beams of bone with dimensions comparable to the lamellar unit were fabricated using focused ion beam (FIB) microscopy and mechanically tested in bending to failure using atomic force microscopy (AFM). A variation in the mechanical properties, including elastic modulus, strength and work to fracture of the micro-beams was observed and related to the collagen fibril orientation inferred from back-scattered scanning electron microscopy (SEM) imaging. Established mechanical models were further applied to describe the relationship between collagen fibril orientation and mechanical behaviour of the lamellar unit. Our results highlight the ability to measure mechanical properties of discrete bone volumes directly and correlate with structural orientation of collagen fibrils.