Acellular Approaches for Therapeutic Delivery: UK Regenerative Medicine Platform Hub Application

Lead Research Organisation: University of Nottingham
Department Name: Sch of Pharmacy

Abstract

Regenerative medicine will transform human health over the next 30 years. We have the ability to create new treatments that repair damaged tissues and restore the body to its original health. Our Hub will play a role in the development of these treatments and thereby help to build a strong UK industry that makes a worldwide impact. We are particularly interested in the methods by which these new treatments are administered to patients. It is difficult to deliver a living cell as a medicine because these cells are fragile and will not form tissue if they experience adverse conditions. We will invent methods to deliver cells to the correct part of the body in an optimal state to repair tissue. Our Hub will create new materials and technologies that can be used in a very large number of future medical applications. In the first phase of our work we will design new materials that recreate the opitmal conditions for stem cells to form tissue. Next we will work with 7 teams who are directly involved in translating new scientific breakthroughs into new medicines. These teams will test our materials and help improve their design by initial studies of suitability for use in Parkinson's Disease, liver diseases, bone repair, skin wound regeneration, cartilage repair, treatments of oesophageal cancer and to assist in anterior cruciate ligament operations.

We are working with leading UK industry to ensure that our technologies can be taken forward as new products that originate in the UK but treat patients across the World.

Technical Summary

Our Hub is concerned with the problem of how a cell or drug therapy for regenerative medicine can arrive at the site of action in an optimal state for rapid and complete tissue formation. Our approach is to design new generations of acellular matrices that create 3D environments that promote tissue formation. We propose that for cell therapies to be efficacious and reliable we must ensure that the cells arrive at the site of action with high viability, minimal physical and biological disruption and with a self-assembling niche that can host, in collaboration with local signals within the patient, spontaneous tissue formation and integration. Overarching scientific principles of these core activities are:

1. The need to mimic hierarchical structures that control cell and tissue behaviour during development and tissue function.

2. Spatial and temporal control of molecular and mechanical stimuli. Tissue morphogenesis and repair use cascades of signalling molecules over periods of hours, days, weeks and months to control cell behaviour. These signals are interpreted by cells in the context of the local mechanical environments and the presence of co-signals (eg integrin mediated cell adhesion).

3.A single cell therapy will encounter numerous changes in environment from manufacture to engraftment. The delivery system should be a chaperone to protect the cell or drug payload against environmental changes.

4. All delivery systems must be able to be translated into clinically and commercially viable products. Therefore, delivery goals should be achieved with the simplest solutions bearing in mind the regulatory process and the risk/benefit of the final product.

Planned Impact

During the first 4 years of the Hub we have planned for a range of early impacts across a wide range of beneficiaries. These include:

TSB Cell Therapy Catapult Centre: We will fully support the early development of the Centre by making available technologies and advise. We believe that the Catapult Centre will be very well placed for early clinical adoption and quality control issues but will need to import expertise and technologies for acellular delivery systems. We will invite the Catapult Centre to be part of our International Steering Committee and will aim to meet at least quarterly with the Centre to explore opportunities.

UK Industry: We have strong industry involvement from day 1 of our Hub and indeed this reflects the fact that all our Hub groups have collaborated with industry for many years. We will communicate openly with all industry and invite new companies into the Hub. IP discussions will need to be undertaken under CDAs. Our Open Conferences will offer new opportunities for companies to get involved and exchange ideas with other companies, clinicians and academics. We will aim to begin the translation of our technologies within the first 4 years of the Hub to enhance future regenerative medicine products

NHS and Clinicians: Our Hub and Spoke model will create opportunities for early clinical translation. Within the first 4 years we expect our first generation acellular technologies (i.e. the systems we developed before the Hub was created) to be integrated into clinical trials. Lead opportunities include anterior cruciate ligament repair and integration into bone with Newcastle and the use of GMP produced human mesenchymal stem cells in autoimmune liver diseases.

General Public and Schools: The outreach programme that we describe in our main proposal will make an impact within the first 4 years on the understanding of regenerative medicine. Using the Royal Society Summer Exhibition (subject to application) and other mechanisms that we have been committed to for many years we will engage with general public to explain, without inappropriately raising expectation, the clinical and commercial potential of the field. We believe that regenerative medicine has a special responsibility to explain science and engineering to Schoolchildren. The field is exciting due to the promise to be the major medical breakthrough of the next 50 years and also exemplifies why biology, chemistry, materials and engineering are so important to their futures. Again our outreach programme ensures impact within 4 years through a Schools programme.

International Community: We want our Hub to be the international centre for delivery systems and acellular technologies and believe that based on our current profile this is a realistic aim. We will engage on an international basis to promote the UK as a centre of excellence in all aspects of regenerative medicine and specifically in the field of our Hub. Our track records show evidence of impact in India (RCUK Science Bridge and Wellcome Trust Affordable Medicines), US (patent licenses), Europe (CE marks, product launches and clinical trials), China (Shanghai Nottingham Advanced Academy and Doctoral training programmes), Japan (joint development of delivery systems) and many others.

Publications

10 25 50

 
Description Dr James Dixon: University of Nottingham/MRC CiC "ImmortaSTEM: Transient Immortalisation for Human Stem Cell Expansion and Therapeutic Application"
Amount £59,972 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 08/2015 
End 02/2016
 
Description Dr Stephen Richardson: A novel regenerative therapy for intervertebral disc degeneration & treatment of back pain
Amount £92,435 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2016 
End 09/2016
 
Description Dr Stephen Richardson: A novel regenerative therapy for intervertebral disc degeneration & treatment of back pain
Amount £20,000 (GBP)
Organisation University of Manchester 
Department Manchester Academic Health Science Centre
Sector Academic/University
Country United Kingdom
Start 09/2016 
End 02/2017
 
Description Partnership Funds via Acellular Hub (Imperial-UCL)
Amount £178,542 (GBP)
Organisation University of Nottingham 
Sector Academic/University
Country United Kingdom
Start 12/2015 
End 05/2017
 
Description Partnership Funds via Acellular Hub (Imperial-UoP)
Amount £118,002 (GBP)
Organisation University of Nottingham 
Sector Academic/University
Country United Kingdom
Start 09/2014 
End 08/2017
 
Description Prof Alastair Sloan: Dentine matrix incorporation into tissue engineering scaffolds for dental tissue repair
Amount £25,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2016 
End 05/2016
 
Description Prof Alastair Sloan: Development of antimicrobial injectable gels for treatment of dental disease
Amount £66,000 (GBP)
Organisation Life Sciences Research Network Wales 
Sector Academic/University
Country United Kingdom
Start  
 
Description Prof Alastair Sloan: Liposomal Delivery of Antimicrobials for Dental cements for Dental Tissue Repair
Amount £50,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 03/2016 
End 09/2016
 
Description Prof Alastair Sloan: Preventing aseptic loosening of cemented joint replacements in older adults: delivery of osteogenic molecules from PMMA bone cement to encourage bone repair and implant osseointegration
Amount £87,000 (GBP)
Funding ID R432/0715 
Organisation The Dunhill Medical Trust 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description 12th International Conference on Materials Chemistry 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact There was good input/feedback afterwards, along with several fruitful discussions.

This was an exciting meeting, and the collaborative discussions were good in general.
Year(s) Of Engagement Activity 2015
 
Description 2016 International Symposium on Nanobiotechnology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This symposium had an excellent focus on nanomaterials and nanotechnologies! Several terrific researchers from around the world attended.
Year(s) Of Engagement Activity 2016
 
Description 4th TERMIS World Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Good conference with several world-leading scientists present.

Good collaborative talks in a great environment - really positive conference!
Year(s) Of Engagement Activity 2015
 
Description APS Pharm Sci 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Good focus on present research in pharmaceutical sciences.

Nice discussions with students and colleagues afterwards.
Year(s) Of Engagement Activity 2014
 
Description Adam Neville Lecture at the University of Dundee 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Great discussions afterwards with several peers.

Met some students interested in the area.
Year(s) Of Engagement Activity 2015
 
Description Australian Health and Medical Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Good discussions on biomaterials-based approaches in regenerative medicine.

The audience was interactive and there were several good discussions afterwards.
Year(s) Of Engagement Activity 2014
 
Description BMES CMBE Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact There were several good discussions on regenerative medicine/biomaterials afterwards.

Good feedback/input from colleagues on our field.
Year(s) Of Engagement Activity 2015
 
Description BSCR and BSGCT Joint Meeting: Cell therapy for cardiovascular disease in the 21st century: a reflective and prospective update 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Good summary of the current status and future direction(s) of cell-based therapies in regenerative medicine.

Nice discussions with other colleagues/researchers.
Year(s) Of Engagement Activity 2015
 
Description BSMB-BRS 3rd Joint Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact There were good discussions around the state of materials for applications in regenerative medicine.

I met some enthusiastic students amongst the collaborative discussions.
Year(s) Of Engagement Activity 2015
 
Description Corday-Morgan Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact This talk was an acceptance of my winning the Corday-Morgan Award.

Recognition of excellence in chemical research: Corday-Morgan Award from the Royal Society of Chemistry.
Year(s) Of Engagement Activity 2015
 
Description EBI-Sanger-Cambridge PhD Symposium (eSCAMPS) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This symposium had an excellent agenda/programme; several terrific discussions on research activities followed.
Year(s) Of Engagement Activity 2016
 
Description EMBO Workshop "Stem cell mechanobiology in development and disease" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This was an excellent workshop, and several collaborative discussions followed this event.
Year(s) Of Engagement Activity 2015
 
Description Fourth International Conference on Multifunctional, Hybrid and Nanomaterials 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact This was an exciting meeting that covered a broad range of topics in research.

Good feedback from colleagues/peers.
Year(s) Of Engagement Activity 2015
 
Description Fourth International Sympsoium Frontiers in Polymer Science 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact There were several good scientists in polymer scientists present - good discussions.

I met with several potential collaborators in the field.
Year(s) Of Engagement Activity 2015
 
Description GRC: Drug Carriers in Medicine & Biology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Great conference - lots of discussion on drug-based approaches in regenerative medicine.

Good collaborative discussions afterwards, which is usual for GRC's.
Year(s) Of Engagement Activity 2014
 
Description GRC: Self-Assembly and Supramolecular Chemistry 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Great assembly of world-leading scientists at this GRC: terrific discussions!

I discussed with a number of collaborators in a great setting.
Year(s) Of Engagement Activity 2015
 
Description Harvard SEAS Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This was an excellent seminar at an excellent venue. I was able to continue collaborative discussions with several world-class scientists and researchers.
Year(s) Of Engagement Activity 2015
 
Description International Conference on Regenerative Biomedical Materials 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Good feedback after talk - nice discussions afterwards.

I met a good group of potential collaborators.
Year(s) Of Engagement Activity 2015
 
Description International Institute for Nanotechnology Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talk well received - several discussions afterwards.

Met several students/possible collaborators - good discussions.
Year(s) Of Engagement Activity 2014
 
Description Joint ChemE/BME Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Good seminar: there were several researchers from Imperial College, with whom I could progress research further along.
Year(s) Of Engagement Activity 2015
 
Description Journal of Internal Medicine (JIM) Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This symposium was very successful in stimulating discussions with several collaborators, some new and several long-standing within Sweden.

Good discussions followed the presentation.
Year(s) Of Engagement Activity 2015
 
Description Kavli Nanoscience Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Collaborative discussions with peers/colleagues.

Discussions based on nanomaterials and materials-based approaches in regenerative medicine.
Year(s) Of Engagement Activity 2014
 
Description London Polymer Network (Plenary Talk) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact This network supported good disucssions amongst several leaders within the field.

I caught up with several peers/colleagues, while I met a number of enthusiastic students.
Year(s) Of Engagement Activity 2015
 
Description MRS Fall Meeting (2015) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This MRS talk was delivered to a large audience, and I connected with several collaborators/researchers from across the globe.
Year(s) Of Engagement Activity 2015
 
Description MRS Spring Meeting and Exhibit (2015) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact There were several world-leading scientists present: great collaborative discussions.

I connected again with a number of collaborators, while I met a number of good students.
Year(s) Of Engagement Activity 2015
 
Description Nanotechnology and Medicines for Tomorrow 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Good discussions about nanomaterials and the field of nanotechnology.

There were several discussions with possible (and current) collaborators.
Year(s) Of Engagement Activity 2014
 
Description New Frontiers in Regenerative Medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Good audience focusing on regenerative medicine; good overview of our research programme.

Nice discussions afterwards on a broad range of topics.
Year(s) Of Engagement Activity 2014
 
Description Royal Society-IBS Research Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Nice conference: met several students and researchers in the field.

Good summary of the field and collaborative discussions.
Year(s) Of Engagement Activity 2014
 
Description SIPCD 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact SIPCD was a good conference - nice discussions with possible collaborators.

Good discussions on science and progress in the field.
Year(s) Of Engagement Activity 2014
 
Description ShanghaiTech Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact A good round of discussions followed afterwards.

There were several colleagues present; nice discussions within the field.
Year(s) Of Engagement Activity 2015
 
Description Swedish Chemical Society Berzelius Days Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This lecture was important for reconnecting with several researchers and clinical collaborators within Sweden.
Year(s) Of Engagement Activity 2016
 
Description UCL Division of Medicine Speaker Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact This symposium was excellent and was attended by a good, multidisciplinary audience. I was able to re-connect with several local collaborators and discuss project ideas.
Year(s) Of Engagement Activity 2016