Biomaterials

A biomaterial is defined as: “a material designed to take a form that can direct, through interactions with living systems, the course of any therapeutic or diagnostic procedure”.

Examples of biomaterials include implants, extracellular vesicles and drug delivery systems.

Biomaterials science is an interdisciplinary study that encompasses the development of novel biomaterials for treatment or diagnostic purposes; understanding how the body interacts with biomaterials; and characterising or replicating naturally derived biological structures.

Aims

With an ageing population and increasing pressures on healthcare services, there is a need for biomaterial technologies to help combat human diseases and improve health. By combining biological and clinical knowledge with engineering approaches, the Biomaterials Research Group aims to:

• enhance our understanding of biological systems and diseases
• use this understanding to develop biomaterials that help treat and diagnose diseases
• clinically translate our research for patient benefit

Projects

Novel antimicrobial and regenerative laser-textured bulk metallic glass implant surfaces

Bulk metallic glasses (BMGs) are alloys that have a disordered atomic structure and are produced by rapidly cooling molten metals to prevent crystallisation.

Due to their unique structure, they exhibit high strength, polymer-like formability and enhanced fatigue/corrosion resistance. This has made BMGs attractive for medical devices (e.g. joint replacements), with initial research demonstrating favourable biocompatibility. When combined with emerging technologies, such as engineered nanotopographies, which renders surfaces antimicrobial/osteogenic, there is potential for a step-change in the field of medical devices.

Little is known, however, how nanopatterning BMGs using laser-ablation, influence its structure, properties and biological responses. This PhD studentship will characterise how laser-ablation influences BMG structure and properties; and optimise surface topographies to prevent bacterial colonisation whilst encouraging bone regeneration.

Development of a nanoscale, near-infrared spectroscopy imaging tool for in situ, rapid and label-free analysis of single extracellular vesicles

Extracellular vesicles (EVs) are cell-derived lipid vesicles containing a complex cargo of proteins, nucleic acids and metabolites that act as a means for local or distant communication between cells. They play a critical role in both health and disease and have also demonstrated significant therapeutic potential.

Constraints to progress in the field of EV research are related to the limitations of existing analytical techniques and importantly their inability to study heterogeneity. Existing techniques are highly labour and time intensive, often requiring specialist training and focus on analysis of bulk samples due to the scarcity and nanometre scale of EVs. The inability of EVs to maintain their structure in dehydrated states also adds further challenges and often results in artefacts.

Using the UK’s first photo-induced force microscopy system (PiFM, part of a £1M EPSRC Strategic Equipment grant) combined with novel probe-enhanced approaches and machine learning algorithms, near infrared (IR) signals and topographical images from individual EVs will be analysed at a nanoscale. This project will provide a theoretical and fundamental experimental basis to underpin a new generation of non-destructive, high-throughput, nano-resolution, life science research and diagnostic tools.

Exploiting bacterial virulence to trigger antimicrobial release from orthopaedic implants

With the number of orthopaedic implant infections on the rise along with the threat of antimicrobial resistance looming, there is a need for smart implant coating technologies that more effectively deliver antimicrobials.

This project aims to achieve this by developing a novel smart implant coating that only releases an antimicrobial in the presence of bacteria. The concept exploits the fact that Staphylococcus aureus, a bacterium that causes joint replacement infections, releases a pore-shaped protein known as alpha-haemolysin. This protein inserts itself in cell membranes causing leakage and cell death. The implant coating consists of the same molecules as cell membranes however it contains a reservoir of antimicrobial within it. When the bacteria release alpha-haemolysin, this creates pores within the implant coating, releasing the antimicrobial and eradicating the infection locally, without the risk of potential antimicrobial resistance.

Influence of modified titanium surfaces on bone repair processes

Through detailed studies involving a series of standardised cell- and tissue-based assays, we have investigated how defined and subtle surface modifications to titanium implant biomaterials can influence osteoblast differentiation.  These studies additionally study cellular activity supporting angiogenesis and appropriate macrophage function, both of which are recognised as pre-requisites for successful bone healing.

Harnessing the potential of Extracellular Vesicles to enhance tissue repair

Extracellular vesicles (EVs) represent membrane surrounded structures released from most cells, where they are proposed to act as transport vehicles to augment paracrine and autocrine delivery of trophic factors.

They are thus presenting themselves as a credible alternative for augmenting tissue regeneration therapies, most notably because EVs do not change their biological phenotype when transplanted at a tissue repair site. Moreover, EVs from dental pulp progenitor cells represent a harvestable bioactive entity that can be used to restore an impaired signalling environment where bone healing is compromised, such as that witnessed with the age-related conditions of osteoporosis and type 2 diabetes.

However, it is recognised that cell phenotype can greatly influence the cargo contained in EVs produced by such cells during culture.  Our work is investigating the growth factor cargo secreted by EVs from mesenchymal sub-populations isolated from dental pulp and how this can differ with respect to their proliferative activity and differentiation status, which in turn can be affected by culture protocols.

Validation of a stem cell derived cartilage model for osteoarthritis research and drug screening

Osteoarthritis is a chronic, progressive joint disorder with 8 million sufferers in the UK alone. Despite overwhelming need, we understand very little about how the disease develops and progresses, there are no tests for early diagnosis, and no treatments beyond pain relief and joint replacement.

Research has previously relied heavily on animal models, which are inefficient, and have produced drugs that fail in clinical trials due to inability to predict human disease. This project aims to address this challenge by developing a scalable in vitro human tissue model using stem cells (primary human chondrocyte progenitor cells). Methods to produce a 3D-tissue akin to articular cartilage will be optimized, and the generated cartilage validated for osteoarthritis research.

Achievements and collaborations

Achievements

Our research group's key achievements to date include:

• patenting liposomal drug delivery system for orthopaedic bone cement
• supporting the successful application for the UK’s first Photo induced Force Microscopy (PiFM) system
• developing an antimicrobial delivery system for metal implants that is triggered by bacterial virulence factors
• optimising methods for detecting enamel erosion using non-contact profilometry
• creating new in vitro natural human tooth models for common dental diseases (erosive tooth wear and dental caries)
• elucidating the osteogenic potential of demineralised dentine matrix
• establishing how manipulation of the neutrophil cell surface topography affects phagocytosis and cell spreading on surfaces

Collaborations

We are proud to have collaborated with organisations across Wales, the UK and beyond, including:

• Renishaw, Gloucestershire, UK
• IK-4 Tekniker, Gipuzkoa, Spain
• Philips, Amsterdam, Netherlands
• Zimmer-Biomet, Bridgend, UK
• Technovent, Bridgend UK
• Unilever, London, UK
• Taicaan Technologies, Southampton, UK