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Cells exposed to ultrasound

Biomaterials & Biomechanics

About our research

Biological materials are exquisitely complex both in terms of their structure and function. Understanding their behaviour and interactions with synthetic materials is critical to successfully engineering new systems, e.g. for drug delivery, neurostimulation or long-term implants for tissue repair and diagnostic monitoring.

There are three complementary themes underpinning our research:

1. Characterisation & Engineering of Biological Membranes

We use specially designed microfluidic systems in which live tissue can be exposed to physical stimuli and simultaneously interrogated using ultra-high speed imaging and quantitative fluorescence microscopy. This enables us to understand how the nanoscale architecture and composition of synthetic materials affect biological processes, e.g. to facilitate drug uptake or stimulation of an immune response.

2. Micro & Nano Encapsulation

We develop new methods for generating micro and nanoscale structures with a high degree of control over both their external and internal dimensions and surface texture. These methods include microfluidic, electrohydrodynamic and hybrid approaches for the simultaneous encapsulation of multiple components in layered structures e.g. to facilitate the programmed release of drugs.

3. Stimuli Responsive Systems for Targeted Therapy

By combining engineering of novel micro and nanostructure with a fundamental understanding of their biophysical interactions with tissue, we can design new systems for localised therapeutic delivery. Examples of how we are applying this research to specific clinical problems can be found below.

Our research areas

Drug loaded microbubbles for targeted delivery to Cancer cells

Antimicrobial Therapy

The 2019 United Nations report on Antimicrobial Resistance (AMR) identifies it as: “one of the greatest threats we face as a global community.” The evolution of drug-resistant bacteria, our over-use of antibiotics and failure to develop new methods for tackling infection could leave us without viable treatments for even the most trivial infections within the next 3 decades. The aim of our team’s research in this area is to confront this challenge through the development of new, sustainable antimicrobial treatments and prevention strategies that minimise the use of antibiotics.

Footprint graphic

Biomechanics

The ability to move around easily and independently is often taken for granted – that is, until injury, disease, or increasing age intervenes, and quality of life declines. A desire to understand how the musculoskeletal system works normally in human locomotion and a need to do something about problems when they arise drives our research in this area. Using motion capture technology, medical imaging, and computer modelling, we study the biomechanics of the lower limbs and investigate how the individual body segments and joints move and interact. We collaborate with colleagues in the areas of orthopaedics, robotics, and computer science.

Magnetic resonance images of a mouse brain before and after low intensity ultrasound exposure. Opening of the blood brain barrier can be seen in the regions where microbubbles are present.

Blood Brain Barrier Disruption

The blood-brain barrier (BBB) continues to represent one of the most significant challenges for successful drug delivery in the treatment of neurological disease. Modulation of structure-activity relationship profiles in drug design have provided only limited clinical success and alternative therapeutic systems are therefore required. In recent years, locally permeabilizing the blood-brain barrier by focused ultrasound has shown considerable promise, with several first-in-human clinical trials reporting successful outcomes for patients with glioblastoma.

Cancer cells following fusion with drug-loaded microbubbles

Cancer

1) Muscle-Invasive Bladder Cancer: The combination of chemo and radiotherapy has been shown to be highly effective in the treatment of muscle invasive bladder cancer. However, the side-effects associated with this treatment can be debilitating and, in many cases, prevent treatment from being successful. A collaborative project has sought to address this challenge by loading chemotherapy drugs into microbubbles.

 

2) Pancreatic Cancer: Pancreatic adenocarcinoma remains one of the most lethal forms of cancer. Treatment options are severely limited by the fact that patients are often only diagnosed when tumours have progressed to an advanced stage and aggressive chemo or radiotherapy cannot be tolerated.

Magnetic Microbubbles Targeted In A Vessel Mimicking Phantom Using A Halbach Array

Cardiovascular Disease

1) Thrombolysis: Stroke remains a leading cause of disability and mortality worldwide. The main treatment options are (i) mechanical removal of blood clots using a specially designed catheter or (ii) the clot-busting drug, tissue plasminogen activator (tPA).

 

2) Pseudoaneurysms: The use of minimally invasive procedures to treat heart and artery problems has increased over the years. These procedures require the insertion of needle(s) in the groin artery to create a so-called “keyhole,” which then provides access for instruments to other locations in the body (such as the heart and the arteries). At the end of these procedures, the keyhole is closed to stop bleeding.

Mechanobiology graphic

Mechanobiology

Mechanobiology is the new and emerging science based on the insight that mechanics is fundamental and essential alongside breakthrough biology for the discovery and translation of novel therapies and interventions for 21 st Century medicine. Oxford Mechanobiology is an interdisciplinary group of engineers, biologists and surgeons designing and building the in vitro discovery technologies that will underpin next generation therapies.

Transmission Electron Micrograph Of Perfluorocarbon Nanodroplets

Orthopaedic Disease

1) Non-Union Bone Fractures: Between 5 and 10% of bone fractures fail to heal completely, resulting in debilitating conditions that have a significant impact upon patients’ quality of life and represent a major financial burden for healthcare services. Existing treatments are highly invasive and rely on the immobilisation of the fracture site. Drugs to promote fracture healing do exist, but are not yet in clinical use due to the risk of off-target effects.

 

2) Alleviating Hypoxia in Rheumatoid Arthritis: As part of our work on microbubble optimisation, we have developed a technique for stably encapsulating oxygen within microbubbles. The oxygen-loaded formulations have been shown to promote the action of sonodynamic therapy drugs for cancer treatment by temporarily raising oxygen levels within tumours.

Beyond Antibiotics: Programme Grant

A five-year long research project funded by the Engineering and Physical Sciences Research Council.

This research is focused on the development of new technology to enable: better characterisation of bacterial infections, rapid point-of-care diagnostics, high-throughput testing of new therapies, alternatives to antibiotics and infection prevention strategies. As recognised by the UN call-for-innovation [1], the creation of this technology represents a critical unmet need. To have a significant impact, it is essential that this development is also integrated with the wider global efforts on tackling AMR. We will achieve this through extensive engagement with AMR research networks and our clinical, industrial and policy partners.

The aim within the 5 year programme is to provide a set of commercially viable and effective technologies to address the need for transformative innovation. Follow the Beyond Antibiotics programme grant progress via our dedicated twitter account linked below and the project website.  

This research is funded by the Engineering and Physical Science Research Council (EPSRC) Programme Grant Scheme under the reference number EP/V026623/1. 

[1] https://www.who.int/antimicrobial-resistance/interagency-coordination-group/IACG_AMR_Invest_ innovation_research_boost_RD_and_access_110618.pdf  

Gone are the days of widespread morbidity and mortality from infectious diseases, yet rising levels of AMR is threatening to make this the future. Without new innovation, a minimum of 5 million people are dying from bacterial AMR each year. We cannot wait a minute longer. https://t.co/rlTmAFP24K

Read about hedgehogs and the evolution of antibiotic resistance. Interesting insights about the possibility to reverse the evolutionary pressures on bacteria to become resistant. https://t.co/pwieBXrKae via @sciam

🦠#AMR researcher Victor Choi's work focuses on "the development of a paradigm-changing ultrasound-responsive antibiotic platform to overcome the inherent limitations of biofilms and deliver efficacious, synergistic, agent-mediated therapy to all kinds of clinical infections." https://t.co/I6ZJvgahot

RT @gardp_amr: Read about the announcement 👉UK leading race to develop new treatments to tackle drug-resistant infections, says Sajid Javid…

"#AMR could be the end of modern medicine as we know it. Common infections will once again kill; organ transplantation, joint replacements, cancer chemotherapy, and care of pre-term infants, will become more difficult or even too dangerous to undertake." - Victor Choi https://t.co/lT1gspgYBG