An integrated biomanufactory and testing platform for studying advanced biosystems in non-ideal environments

Engineered bioactive polymers (containing living matter or acellular) are the next generation of industrial materials, due to their ability to self-regulate, self-heal and process energy. These engineered biosystems, which hold promise for many regenerative medical interventions, are being increasingly used for tissue deterioration, mitigating trauma and enhancing healing. They can address additional healthcare challenges (such as the global shortage of transplantation tissue), by acting as substitutes which can simultaneously restore the biomechanics of an affected site and the original biochemistry; therefore, minimising rejection and enhancing integration with surrounding tissues.

These bioengineered constructs are, however, inherently complex and composed of multiple phases and states, which can undergo significant morphing when exposed to minor fluctuations in the physiological conditions they were designed for. These can include the harsh immunological microenvironment in the body following implantation or during pathologies; or the physical environment when manipulated in non-ideal climates (in emergency medicine, in space or in natural disaster/climate-change affected areas).

There is a lack of capabilities that can evaluate and predict the dynamics of engineered biosystems in these extreme conditions (biological or physical) – these properties are essential for their bioactivity. Such a tool could help with validation, improving manufacture and exploiting the environmental conditions to generate biological constructs with enhanced functionalities and greater stability. Importantly, it would provide a tool to study the interaction of biopolymers with living matter (i.e. human cells) which is important for producing advanced hybrid systems with clinical potential.

At the University of Birmingham, we pioneered several bioengineered models (such as bone organoids [1] and long-term organotypic culture [2]) that can be employed to study both pathological states and the biological response to extreme environments (e.g. simulated microgravity [1]). These biopolymer-based, ‘humanised’ systems, based on 3Rs approaches, were designed also for applications in regenerative medicine by combining typically used surgical reconstruction ceramics and haemostatic agents.

We are looking to develop a new technology that will allow us to concomitantly produce and assess the real-time environmental responses of these/similar biosystems, using state-of-the-art physico-chemical analysis. This apparatus will also allow us to determine the biomaterial effects on cellular physiology, viability and behaviour.

The project will combine tissue engineering and culture techniques with remotely-controlled manufacturing elements and an array of testing units that will assess the kinetics and microstructure of these systems in ideal and non-ideal conditions. The sample microenvironment will be manipulated using a series of biochemical, thermal, vibration-induced and simulated microgravity capabilities. Subsequently, these systems will be assessed in terms of their bioregenerative potential using advanced in-vitro models (organotypic and multi-cellular).

The work will combine optical and mechanical diagnostics with in-depth biochemical characterisation to examine the morphological and biological responses (e.g. high resolution cell microscopy, molecular/genetic analysis, particle tracking analysis, rheology, uXRF, uCT, XRD, spectroscopy). The project will also include CFD and coupled CFD-DEM simulations to allow the exploration of a broader and denser parameter space than is accessible through the experiment alone.

This project would suit a candidate with a background in (bio)physics, chemical/mechanical engineering or mechatronics. Experience in programming and computer modelling is also desirable. Full training will be provided in all areas, including the handling of biological components and the generation of biological models.

Funding notes:

Studentships include: Full tuition fees (at UK rate) * a tax free annual stipend (in academic year 2023-24 this was £18,622.00)** a travel allowance in year 1 a travel / conference budget a generous consumables budget use of a MacBook Pro for the duration of the programme.

References:

[1] Iordachescu A. et al. Trabecular bone organoids: a micron-scale ‘humanised’ prototype designed to study the effects of microgravity and degeneration. npj Microgravity (2021) [2] Iordachescu A. et al. An In Vitro Model for the Development of Mature Bone Containing an Osteocyte Network. Advanced Biosystems (2018)