A COVID-19-Based Modified Epidemiological Model and Technological Approaches to Help Vulnerable Individuals Emerge from the Lockdown in the UK.

COVID-19 has shown a relatively low case fatality rate in young healthy individuals, with the majority of this group being asymptomatic or having mild symptoms. However, the severity of the disease among the elderly as well as in individuals with underlying health conditions has caused significant mortality rates worldwide. Understanding this variance amongst different sectors of society and modelling this will enable the different levels of risk to be determined to enable strategies to be applied to different groups. Long-established compartmental epidemiological models like SIR and SEIR do not account for the variability encountered in the severity of the SARS-CoV-2 disease across different population groups. The objective of this study is to investigate how a reduction in the exposure of vulnerable individuals to COVID-19 can minimise the number of deaths caused by the disease, using the UK as a case study. To overcome the limitation of long-established compartmental epidemiological models, it is proposed that a modified model, namely SEIR-v, through which the population is separated into two groups regarding their vulnerability to SARS-CoV-2 is applied. This enables the analysis of the spread of the epidemic when different contention measures are applied to different groups in society regarding their vulnerability to the disease. A Monte Carlo simulation (100,000 runs) along the proposed SEIR-v model is used to study the number of deaths which could be avoided as a function of the decrease in the exposure of vulnerable individuals to the disease. The results indicate a large number of deaths could be avoided by a slight realistic decrease in the exposure of vulnerable groups to the disease. The mean values across the simulations indicate 3681 and 7460 lives could be saved when such exposure is reduced by 10% and 20% respectively. From the encouraging results of the modelling a number of mechanisms are proposed to limit the exposure of vulnerable individuals to the disease. One option could be the provision of a wristband to vulnerable people and those without a smartphone and contact-tracing app, filling the gap created by systems relying on smartphone apps only. By combining very dense contact tracing data from smartphone apps and wristband signals with information about infection status and symptoms, vulnerable people can be protected and kept safer.

Mechanical stretch and chronotherapeutic techniques for progenitor cell transplantation and biomaterials.

In the body, mesenchymal progenitor cells are subjected to a substantial amount external force from different mechanical stresses, each potentially influences their behaviour and maintenance differentially. Tensile stress, or compression loading are just two of these forces, and here we examine the role of cyclical or dynamic mechanical loading on progenitor cell proliferation and differentiation, as well as on other cellular processes including cell morphology, apoptosis and matrix mineralisation. Moreover, we also examine how mechanical stretch can be used to optimise and ready biomaterials before their implantation, and examine the role of the circadian rhythm, the body's innate time keeping system, on biomaterial delivery and acceptance. Finally, we also investigate the effect of mechanical stretch on the circadian rhythm of progenitor cells, as research suggests that mechanical stimulation may be sufficient in itself to synchronise the circadian rhythm of human adult progenitor cells alone, and has also been linked to progenitor cell function. If proven correct, this could offer a novel, non-intrusive method by which human adult progenitor cells may be activated or preconditioned, being readied for differentiation, so that they may be more successfully integrated within a host body, thereby improving tissue engineering techniques and the efficacy of cellular therapies.

The effect of PLGA doping of polycaprolactone films on the control of osteoblast adhesion and proliferation in vitro.

Poly(epsilon-caprolactone) (PCL) film was modified using specified amounts of poly(d,l-lactide-co-glycolide) (PLGA) to provide a means to control polymer degradation. The aim of the study was to determine the effects of doping PCL with PLGA on the materials degradation, morphology and cell adhesion, to determine the significant variables within the process that could provide further control of cell adhesion. PLGA-doped PCL films were aged in osteogenic medium at 37 degrees C for up to 28 days. The aged samples were analysed in terms of weight loss or weight gain, molecule deposition and surface morphology. Molecule deposition was determined using Fourier transform infrared spectroscopy in attenuated total reflectance mode (FTIR-ATR) and morphology was determined using scanning electron microscopy and interferometric microscopy. The loss of the PLGA doping during degradation enhanced the formation of nano-porous structures in the remaining PCL domains, which attracted the deposition of substances from the osteogenic medium, which favoured the attachment and growth of human osteoblasts. The growth of osteoblasts was influenced by the controlled release of acidic products through polymer blending. Two pairs of FTIR-ATR absorption bands at 1090 and 1110 cm(-1), and at 1180 and 1190 cm(-1) were found to correlate to both PLGA and PCL, respectively. Changing the level of PLGA doping in PCL provided an approach to control the acidic products which can direct the growth of osteoblast cells.

The effect of particulate material on the regulation of chemokine receptor expression in leukocytes.

Cellular chemotaxis is one of the most significant components of the host response to implanted materials. However, the effect of materials and their particulates on the regulation of chemokine receptor expression is not well known. This study investigated the effects of alloy particulates on the regulation of CXCR1 and CXCR2 expression on leukocytes from whole blood and purified leukocyte cultures. The volumetric particle concentration and opsonisation dependent manner of CXCR1 and CXCR2 expression on neutrophils and CCR1 and CCR2 expression on monocytes/macrophages was analysed using both flow cytometry (FACS) and real time-PCR. Variation in volumetric concentrations of particulates demonstrated that cell:particulate ratios of 1:1 of non-opsonised NiCr alloy induced the down regulation of CXCR1, and 1:0.25 of opsonised NiCr induced the up regulation of CXCR2. CoCr alloy particulates had no effect on CXCR expression. This study demonstrated that the regulation of chemokine receptor expression could be effected by the properties of materials and the expression of these receptors may contribute to host cellular reactions such as chemotaxis. This study also demonstrated that the response of leukocytes can be demonstrated using a whole blood assay for the study of chemokine receptor expression after direct contact with materials.

The design and production of Co-Cr alloy implants with controlled surface topography by CAD-CAM method and their effects on osseointegration.

Improved fixation and increased longevity are still important performance criteria in the development of orthopaedic prostheses. The osseointegration of a series of implant designs made of conventional cobalt-chromium alloy was investigated, the shape of each implant being the critical variable. The shape was defined by computer-aided design with a view to maximising interdigitation of new bone with the implant. Two different process routes, conventional casting and selective laser sintering were employed, each process yielded implants that had identical surface topology but different microstructures. Hydroxyapatite (HA) was used to coat some samples by plasma spraying. Bone formation associated with each implant design was delineated through the administration of fluorescent vital dyes at three time points following their implantation into New Zealand white rabbits. After one month, specimens were harvested, resin embedded, serial sectioned and examined under fluorescent light microscopy. The amount of bone growth was quantified using image analysis. Plasma spray HA-coated samples promoted better osteogenesis and integration than uncoated samples. The extent of bone growth associated with identically shaped specimens fabricated by the SLS route was markedly greater, attributed to the microstructure of these implants.

The inflammatory potential of biphasic calcium phosphate granules in osteoblast/macrophage co-culture.

Some biological properties of a range of biphasic calcium phosphate (BCP) granules were quantified using a co-culture model of primary unstimulated human osteoblasts and macrophages. The BCP granules were classified in terms of diameter and the ratio of tricalcium phosphate (TCP): hydroxyapatite (HA). All granules were 50% porous and sterilised by gamma-irradiation. Primary unstimulated human osteoblasts and macrophages were cultured in contact with the range of BCP granules for 1, 7 and 14 days. The response of the cells was determined and quantified by the assessment of viable cell adhesion to the substrate, using lactate dehydrogenase assay, and the production and release of the cytokines; interleukin 1beta, (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and prostaglandin E2 (PGE2). Throughout the test period viable cell adhesion on all BCP granules was significantly lower than the tissue culture polystyrene control. Higher content TCP materials, (80% and 100% TCP) did not support viable cell adhesion after 1 day, lower content TCP materials, (20% and 50% TCP) granules did support viable cell adhesion throughout the time period. The percentage content of TCP was a more significant factor than granule size within the test conditions at all time points.