Soft implants as medical devices Researchers in the BIOELECTRIC project are working to develop a biocompatible, soft bioelectric implant that can secrete ions and molecules. This work could open up new possibilities in the treatment of a variety of medical conditions, as Professor Hagan Bayley explains. A lot of communication in the body occurs through small molecules, such as hormones and neurotransmitters, or ions, such as chloride, sodium and calcium ions, which influence physiological processes by binding to receptors or affecting electrical activity. As the Principal Investigator of the EU-backed BIOELECTRIC project, Professor Hagan Bayley is working to develop a soft, bioelectric implant capable of secreting these molecules and ions in the body. “We want to make a device that can secrete molecules or ions in a spatially controlled manner, and be able to turn secretion on-and-off at will,” he outlines. Such a device holds wide therapeutic potential, for example in delivering therapeutics to accelerate wound healing or regenerate the spinal cord, yet Professor Bayley says the aim of the project is to develop a general technology rather than focus on a specific application. “We’re trying to devise a platform device that can be used for many different applications,” he says. Synthetic tissues as implants This research builds on earlier work on a class of membrane proteins called protein pores, which can be used as sensors. A spin-off company, Oxford Nanopore, was established by Professor Bayley in 2005 to bring a platform sensing technology based on protein pores to the market. The company developed the MinION nucleic acid sequencer, while Professor Bayley and his colleagues at the University of Oxford moved on to pursue other avenues of investigation. “We took our interest in membrane proteins to make synthetic tissues. The idea was to use a 3-D printer to pattern tiny aqueous droplets with a volume of around 50 picolitres [2013 Villar]. We can get these compartments to communicate with each other by using protein pores,” he explains. “Living tissues comprise communicating cells and hence the printed materials behave as synthetic tissues [2019 Bayley; 2021 Alcinesio], which can be used as implants.” These materials are made using naturallyoccurring lipids to ensure biocompatibility, and then encapsulated in polymers to
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area that’s not accessible to light, you might use magnetism or orally administered small molecules to activate the devices,” says Professor Bayley. The researchers have found it is relatively easy to make implants that can be turned on, but turning them on-and-off in a controlled manner is proving more challenging. Further, while it is fairly simple to secrete ions from the implants, Professor Bayley’s group is also looking at whether they can carry other therapeutics. “We would like the implants to secrete specific small molecules, or even to make small molecules and then secrete them. We’re trying to implement all of these ideas,” he says. The focus is on investigating fundamental ideas with the potential to propel advances in tissue engineering. “As well as the implants, we continue to work on synthetic tissues and printed living cells [2020 Zhou] capable of communicating with each other, also for medical applications,” continues Professor Bayley. The ultimate goal in this research is to produce devices that can aid the treatment of different medical conditions. The treatment of spinal cord injury is typically broken down into two main categories. “In one category the spinal cord is completely severed, which is currently very difficult to fix. If we could get nerves to re-grow consistently across a break in the spinal cord then that would be a considerable advance,”
says Professor Bayley. Partial damage to the spinal cord is usually more treatable, but Professor Bayley says it’s important that it’s addressed before the situation deteriorates. “If you just let matters take their course, often it doesn’t work out well,” he stresses. “If we can intervene, with an implant that stimulates local cellular growth, that would be very beneficial.”
Affordability The cost of the device is also an important consideration in BIOELECTRIC, with a view towards the wider application of soft implants and the establishment of a spinoff company to build on the project’s work. Not only does Professor Bayley aim to produce devices that can benefit patients, he also wants to drive the price down so they’re affordable, which is not always the case with new medical technologies. “For example CAR (Chimeric Antigen Receptor) T-cell treatments are very expensive. They are extremely important therapies, and are a massive breakthrough in cancer treatment, but they are hugely expensive,” he says. This is a situation that Professor Bayley is keen to avoid. “We want to drive the cost of anything we develop down to a reasonable level. We don’t want these devices to cost millions,” he stresses. “We try to use relatively simple building blocks that will be affordable.”
A 3D-printed structure formed of droplets. The blue droplets contain a small molecule, which can be secreted through protein pores in the pattern of a cross.
make the implants more robust. This is an important consideration when an implant is employed over a long period, although there are also possible applications where the implant might have a shorter lifespan. “For example, if we want to use one of these implants for wound healing then we would want it to be degraded by the body over a
The device works according to broadly the same basic principles in these two cases, but with refinements that are relevant to the specific application. It’s important to demonstrate that the technology can be used to solve specific problems if it is to be commercialised, but at this stage Professor Bayley and his colleagues are looking more
generally to develop and improve the device, bringing together several strands of research. “We’re exploring several different ideas,” he says. One important issue in the project is to control the implants from outside the body, without the need for lots of wires or other paraphernalia. “If these devices are relatively near the surface of the body, then you will be able to control them with light. If they are implanted in an
EU Research
A Soft Bioelectric Implant from Droplet Networks Project Objectives
The aim of the BIOELECTRIC project is to develop soft bioelectric implants using biocompatible materials, overcoming some of the issues associated with using stiff or metallic materials. Much of the research is centered on trying to control these implants externally, so that they can release ions and small molecules at particular times and particular locations for therapeutic purposes. The implants might be used in regenerating the spinal cord for example, or in healing wounds, or even to replace the retina. Researchers aim to make these implants more robust for long-term applications by encapsulating them in various polymers, while in other applications it may be desirable for the implants to disintegrate after a short lifetime.
Project Funding
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Grant Agreement No. 957516.
Contact Details
Project Coordinator, Professor Hagan Bayley FRS Professor of Chemical Biology University of Oxford 12 Mansfield Road, Oxford, OX1 3TA T: + 01865 285100 E: hagan.bayley@chem.ox.ac.uk W: https://www.bayleygroup.co.uk/ Villar, G., Graham, A.D. and Bayley, H. A tissue-like printed material. Science 340, 48-52 (2013). Zhou, L., Wolfes, A.C., Li, Y., Chen, D.C.W., Ko, H., Szele, F.G. and Bayley, H. Lipid bilayer supported 3D printing of human cerebral cortex cells reveals developmental interactions. Advanced Materials 32, e2002183 (2020). Alcinesio, A., Cazimoglu, I., Kimmerly, G.R., RestrepoSchild, V., Krishna Kumar, R. and Bayley. H. Modular synthetic tissues from 3D-printed building blocks. Adv. Functional Materials, 2107773 (1-11) (2021). Review: Bayley, H., Cazimoglu, I. and Hoskin, C. Synthetic tissues. Emerging Topics in Life Sciences 3, 615-622 (2019).
Professor Hagan Bayley
We want to make a biocompatible device that can secrete ions and molecules. Further, we’d like to control secretion, to turn it on and off when we want to. few days,” says Professor Bayley. The aim is to develop a flexible technology that can secrete different therapeutics and therefore be used in different applications. “If you want to treat a spinal cord injury, you might want a device that secretes peptide growth factors, while if you’re trying to accelerate wound healing, you might want to secrete a combination of antibiotics,” explains Professor Bayley.
BIOELECTRIC
Hagan Bayley is the Professor of Chemical Biology at the University of Oxford. He was the 2009 Chemistry World Entrepreneur of the Year and was elected a fellow of the Royal Society in 2011. His lab has developed techniques for the fabrication of 3D tissues, both living and synthetic.
A simplified schematic of a 3D droplet printer. Pulses from piezo ejectors produce picoliter droplets, which can be printed in a patterned manner.
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