Self-triggered smart biomaterials

Polymeric biomaterials, which are typically synthetic substances introduced into body tissue as part of an implanted medical device or used to replace an organ or bodily function, are increasingly ubiquitous in healthcare. The introduction of biomaterials brings with it a risk of infection from microorganisms, representing a major risk to patients and burden to the NHS requiring extended, complex treatments, which are often unsuccessful. With infection rates approaching 100% in some devices, there is an urgent unmet need to develop ways to prevent bacterial biofilms forming on the surface of medical devices.

Typically, infection involves initial attachment of bacteria to the surface of the biomaterial, followed by colonisation through subdivision and growth into a biofilm. This biofilm is highly resistant to treatment by antibiotics, and acts as a reservoir for further spread of infection in the body. This can lead to sepsis and death.

To effectively address the problem of biofilm development in biomaterials, this project has two key aims in the development of smart materials-those which are responsive to a stimulus such as light (applied externally) or the onset of infection (where the stimulus is internal).

Firstly, we seek to build on a previous EPSRC project, and some further recent results from our lab, which represents a new way to kill any bacteria which may still be able to attach to the polymer. This uses a combination of visible light and photosensitisers - a class of molecule which can use light to catalytically produce reactive oxygen, which is highly effective at killing bacteria. A key point in using this chemistry is that the range of active species are able to attack a wide range of targets in bacteria, rather than a single mode of action, which is a limitation of traditional approaches, such as antibiotics. As such, the approach gets round the issue of development of antimicrobial resistance, and has a long lived effect, which should allow it to be supported by clinicians in the future.

In this strand, we will use synthetic chemistry, materials science and engineering methods in extrusion to develop new ways to incorporate photosensitisers at the direct point of bacterial attachment - the medical device surface. We will use multi-layered extrusion techniques to make thin coatings on substrates used to manufacture traditional medical devices, such as PVC. We will tune the efficiency of this system to maximise production of reactive oxygen, and carry out a full chemical and physical characterisation of the light-induced processes and how effectively they kill bacteria.

Secondly, in a linked approach, we will build on interesting recent results which show we can use pH to control rate of cleavage of a model drug substance from a polymer suitable for use in medical device applications. A change in pH is observed at the onset of infection in urinary catheter infections in particular, so there is an opportunity to develop materials which are able to kill a bacterial infection in response to its own development, thereby stopping the infection in its tracks. Using synthetic chemistry, we will develop new 'building blocks' for polymers which can be used to make a responsive coating to a current medical device material. This will allow us to engineer polymers which are inherently able to resist the attachment of bacteria. In practice, this involves polymer synthesis to make our new candidate materials, then characterising their surface chemistry using a range of spectroscopic, microscopic and physical methods. We will then assess the ability of the materials to resist bacterial attachment by trying to grow biofilms of bacteria which typically cause infections.

Together this will allow us to develop materials which may be incorporated in or on medical devices such as endotracheal tubes, urinary catheters, or intraocular lenses, which would have wide impact for patients and medical device companies.