Analytical and computational studies predict negligible risk of cell death from eddy generation off flat surfaces in cell culture flow systems

Cell-based therapies represent the current frontier of biomedical innovations, with the technologies required underpinning treatments as broad as CAR-T cell therapies, stem cell treatments, genetic therapies and mRNA manufacture. A key bottleneck in the manufacturing process for each of these lies in the expansion of cells within a bioreactor vessel, requiring by far the greatest share of time for what are often time-critical therapies. While various designs, culture feeding and mixing methods are employed in these bioreactors, a common concern among manufacturers and researchers lies in whether shear stresses generated by culture media flow will damage cells and inhibit expansion. This study develops an analytical tool to link macro-scale measures of flow to risk of cell death using relationships with eddy size and dissipation rates, from eddies generated off flat surfaces. This analytical tool was then employed using computational fluid dynamics (CFD) to replicate a range of generic bioreactor geometries and flow conditions. We found that no combination of flow condition or design parameter was predicted by the tool to cause cell death within eddies, indicating negligible risk of cell death due to eddy formation within cell culture systems. While this requires experimental validation, and does not apply when cells are expanded using microcarriers, this tool nonetheless provides reassurance and accessible prediction of bioreactor design parameters that could result in cell death. Finally, our findings show that bioreactor design can be tailored such that the shear stress stimulation of cells can be selectively altered through small changes in flow rate

An argument for pandemic risk management using a multidisciplinary One Health approach to governance: an Australian case study

The emergence of SARS-CoV-2 and the subsequent COVID-19 pandemic has resulted in significant global impact. However, COVID-19 is just one of several high-impact infectious diseases that emerged from wildlife and are linked to the human relationship with nature. The rate of emergence of new zoonoses (diseases of animal origin) is increasing, driven by human-induced environmental changes that threaten biodiversity on a global scale. This increase is directly linked to environmental drivers including biodiversity loss, climate change and unsustainable resource extraction. Australia is a biodiversity hotspot and is subject to sustained and significant environmental change, increasing the risk of it being a location for pandemic origin. Moreover, the global integration of markets means that consumption trends in Australia contributes to the risk of disease spill-over in our regional neighbours in Asia-Pacific, and beyond. Despite the clear causal link between anthropogenic pressures on the environment and increasing pandemic risks, Australia’s response to the COVID-19 pandemic, like most of the world, has centred largely on public health strategies, with a clear focus on reactive management. Yet, the span of expertise and evidence relevant to the governance of pandemic risk management is much wider than public health and epidemiology. It involves animal/wildlife health, biosecurity, conservation sciences, social sciences, behavioural psychology, law, policy and economic analyses to name just a few. The authors are a team of multidisciplinary practitioners and researchers who have worked together to analyse, synthesise, and harmonise the links between pandemic risk management approaches and issues in different disciplines to provide a holistic overview of current practice, and conclude the need for reform in Australia. We discuss the adoption of a comprehensive and interdisciplinary ‘One Health’ approach to pandemic risk management in Australia. A key goal of the One Health approach is to be proactive in countering threats of emerging infectious diseases and zoonoses through a recognition of the interdependence between human, animal, and environmental health. Developing ways to implement a One Health approach to pandemic prevention would not only reduce the risk of future pandemics emerging in or entering Australia, but also provide a model for prevention strategies around the world

Influence of contact pressure, cross-shear and counterface material on the wear of PEEK and CFR-PEEK for orthopaedic applications

Total joint replacement is a successful surgical intervention for the treatment of the degeneration of many joints, particularly the hip and knee. As the demand for joint replacement grows, and the life expectancy of the population increases, the performance requirements of these implants also changes. New materials, to improve longevity and enhance performance have been explored including PEEK and CFR-PEEK. This study investigated whether CFR-PEEK and PEEK were appropriate materials for total joint replacement by examining wear performance in simple configuration studies articulating against cobalt chrome under a range of cross-shear and contact pressure conditions. Simple geometry pin on plate studies were conducted for one million cycles for each test condition, with the contact pressure and cross-shear conditions representing a range in which the material may need to operate in-vivo. The wear factor for PEEK was significantly higher than CFR-PEEK and conventional polyethylene under all test conditions. Both PEEK and CFR-PEEK wear were influenced by contact pressure, with the highest wear factors for both materials measured at the highest pressure conditions. PEEK appeared to have a cross-shear dependent wear response, but this was not observed for the CFR-PEEK material. This study has further characterised the wear performance of two materials that are gaining interest for total joint replacement. The wear performance of the PEEK material showed poorer wear performance compared to polyethylene when articulating with a metal counterface, but the performance of the CFR-PEEK material suggested it may provide a suitable alternative to polyethylene in some applications. The wear performance of CFRPEEK was poorer than polyethylene when it was used as the plate, when there was translation of the contact zone over the surface of the CFR-PEEK plate. This has implications for applications in low conforming contacts, such as lower conformity knee replacement

Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications

In eccentric exercise the contracting muscle is forcibly lengthened; in concentric exercise it shortens. While concentric contractions initiate movements, eccentric contractions slow or stop them. A unique feature of eccentric exercise is that untrained subjects become stiff and sore the day afterwards because of damage to muscle fibres. This review considers two possible initial events as responsible for the subsequent damage, damage to the excitation-contraction coupling system and disruption at the level of the sarcomeres. Other changes seen after eccentric exercise, a fall in active tension, shift in optimum length for active tension, and rise in passive tension, are seen, on balance, to favour sarcomere disruption as the starting point for the damage. As well as damage to muscle fibres there is evidence of disturbance of muscle sense organs and of proprioception. A second period of exercise, a week after the first, produces much less damage. This is the result of an adaptation process. One proposed mechanism for the adaptation is an increase in sarcomere number in muscle fibres. This leads to a secondary shift in the muscle's optimum length for active tension. The ability of muscle to rapidly adapt following the damage from eccentric exercise raises the possibility of clinical applications of mild eccentric exercise, such as for protecting a muscle against more major injuries