Engineering growth factor microenvironments - a new therapeutic paradigm for regenerative medicine

Growth factors are molecules within our body that participate in many physiological process that are key during development as they control stem cell function. These molecules thus have the potential to drive the regeneration of tissues in a broad range of medical conditions, including in musculoskeletal (bone repair), haematological (bone marrow transplantation) and cardiovascular (infarction, heart attack) diseases. Growth factors are currently produced commercially and are used regularly in clinical applications. However, they are very power cell signalling molecules and dose is critical as balance between effect and safety has to be considered. To date the use of growth factors in regenerative medicine has been only partially successful and even controversial. The growth factors are rapidly broken down and cleared by the body. This makes prolonged delivery (as is required to effect repair) a problem and typically higher than wanted doses are administered to get around this. While their help in regeneration is undoubted, collateral side effects can be catastrophic e.g. tumour formation.
We have developed new technology that directly addresses these concerns as it uses materials (that can be topically implanted) to deliver low, but effective, growth factor doses; this programme is about the safe use of growth factors in clinical applications. This will not only reduce risks for patients who currently receive growth factor treatments, but will open up therapies that can include co-transplantation with stem cells to a wider range of patients as doctors would not have to keep these therapies back for cases of most pressing need. This increased use would minimise costs as growth factors are very expensive and reduced dose would save money per treatment.

Our approach is unique and this programme grant will allow us to enhance the UK's world leading position through innovative bioengineering. We know that stem cells have huge regenerative potential and that growth factors provide exquisite stem cell control - both are currently untapped. We will engineer new materials to enable growth factor technology, and critically stem cell technologies, where traditional approaches are falling very short of the mark.

Laboratory
We will produce a range of new techniques, tools and technologies that will find broad application in laboratories. This will include:
-Novel cell culture platforms specifically designed around the needs to stem cells rather than fastidious cells. A dynamic phenotype is important for the use of stem cells. However, in culture this results in a rapid loss of stem cell phenotype and presents scale up challenges for autologous therapies.
- Our precision measurement and sensing research will enable non-invasive, label free approaches.

Industry/Pharma
The potential for growth factor (GF) driven regeneration in clinic is massive. However, it is currently limited due to lack of ability to administer these powerful drugs with efficiency and safety. Despite safety concerns, products are still widely used and the market still flourishes. If safety concerns can be addressed and efficiency of action increased, the market would clearly expand from a >£1B market to a multi-£B market. We identify SMEs/stake holders within each of our grand challenges: musculoskeletal (Taragenyx, Locate Therapeutics, Nanokick), haematology (SNBTS) and cardiovascular (Clyde Bioscences) and we have the Senior Director of Johnson & Johnson Medical Device Innovation as an advisor. These partners will help us to realise this market potential.
Further:
- Our ability to control stem cells will go beyond laboratory and find use in biotechnology for industrial scale stem cell expansion.
- Our 3D environments will find use in drug screening and gene therapies coming out of the Pharma sector. This will be replace much expensive animal testing allowing a cheaper Pharma workflow through selection of better drug leads for animal testing.
- Building in vivo sensors/ clinical sensors for diagnostics, toxicology and delivery visualisation.

Health Service Providers
Our strategy involves dramatic reduction of the GF dose (~ 500 times) which will increases cost-effectiveness of these very expensive signalling molecules (e.g. BMP treatment, which can cost up to £3k per patient). This new technology will dramatically reduce the cost of these therapies and this will facilitate the larger range of conditions that GFs can be used in as we address safety issues. It will further open up new delivery systems for prolonged administration saving further surgical procedures and we will also aim to discover other, cheaper, drugs (metabolites) that can further reduce growth factors costs through synergistic action.

Patients
The research will have clear impact on patients. It will remove safety issues from growth factor use and will thus increase the range of conditions growth factors can be used in. Further, the public now expect stem cell technologies to be made available but platforms for stem cell growth and delivery are not currently easily ready. We can deliver these platform technologies to facilitate wider uptake of stem cell treatments by health service providers through increasing quality of stem cell therapies and driving down costs. Further, our approaches are amenable to personalised/stratified approaches. Patients stem cells can be tested for optimal response to different growth factors on our surfaces and, indeed their own proteins and growth factors will be compatible with our technologies. Non invasive diagnostics and monitoring will also be developed.

Public
Our work will be of benefit to the general public, raising interest in science, educating about the challenges faced by researchers, increasing funding for research, increasing awareness of the burden of degenerative diseases in a broad range of fields e.g.: musculoskeletal, cardiovascular, blood related conditions. We inspire the next generation of scientists and clinicians to overcome the burden of disease in this area.

Policy
We will strive to ensure that bioengineering approaches are prioritised and ready the technology for clinical uptake.