Acellular / Smart Materials - 3D Architecture: UK RMP Hub

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

We have identified a significant unmet need for improved therapies to treat tissue degenerative diseases and injuries in eye, liver and musculoskeletal tissue. These conditions represent a considerable obstacle to health and quality of life, as well as a staggering burden to the economy. We will combine the expertise of world-leading UK research groups to design and manufacture innovative biomaterials and drug delivery strategies to develop the needed therapies. Importantly, the focus will be on accelerating the process of translating our scientific discoveries and advances into real-world applications.
Our strategy stems from research on smart materials for specific clinical applications in eye, liver and musculoskeletal repair. We will investigate a range of highly innovative materials that can be tailored according to the specific clinical needs. We will develop exciting smart technologies where implanted materials will react to internal or external stimuli to, for example, release drugs that improve wound healing and reduce inflammation, or growth factors to enhance the regeneration of damaged or lost tissue. We will design flexible material platforms that can be easily modified to achieve a wide range of complex functionalities. We will introduce advanced manufacturing routes to produce materials that mimic the complex structure and multi-functionality of biological tissues. For applications in eye repair, we will develop injectable polymer sheets embedded with cells that would simultaneously replace lost retinal pigment epithelium and photoreceptors which cause visual impairment. We will also build 3D tissue engineered constructs for corneal repair. For our work on musculoskeletal tissue, we will develop injectable materials and 3D printed scaffold materials to repair fractures and defects in long bones, for example the tibia. The structure of the scaffolds will be designed to support and increase bone formation while embedded nanoparticles will be used for controlled delivery of growth factors. Our second target in the musculoskeletal tissue is shoulder rotator cuff repair where we have already novel electrospun material technologies in clinical trials. Here, we will improve these materials by introducing bioresponsive cues to regulate the activity of cells, modulate inflammation, enhance the formation of blood vessels and promote tissue growth. For osteoarthritis treatment, we will develop 3D constructs with controlled gradients that promote physical organisation of cartilage resulting in a more native-like functional material. The third clinical application targeted in this project is liver repair. We will aim to improve transplantation therapies by focussing on three promising pathways: 1) extending graft life-time using microparticles for localised delivery of immunomodulatory compounds, 2) enhancing cell engraftment with localised release of growth factors, and 3) developing innovative anti-fibrosis materials, including gels, patches and sprays. Importantly, we will complement our development pipeline with research on materials safety and immune response.
Through the UKRMP2 Acellular Hub we will steer our research towards applications with high success potential in alignment to identified clinical needs, manufacturing feasibility, regulatory compliance and product safety assurance.

Technical Summary

In UKRMP2 Acellular we will develop and evaluate new classes of smart biomaterials for application in tissue regenerative therapies in three important clinical areas: eye, liver and musculoskeletal repair. The Hub structure is composed of 4 work packages (WPs) designed to maximise end clinical impact and 3 Strategic Gates as critical checkpoints. In WP1, we will develop a platform of innovative designer materials that enable tissue formation while simultaneously providing biological and biophysical cues for differentiation and hierarchical organisation of well vascularised tissues. The materials development pipeline will be complemented by research into advanced manufacturing strategies to develop 3D tissue engineered porous scaffolds and hierarchical structures. The research will be informed by immunological and safety considerations to enhance the translation potential. Importantly, the specific design parameters for the materials are defined by the clinical need (informed) and outlined in WPs 2-4 which focus on the three clinical exemplars, namely the eye, musculoskeletal repair and the liver. We aim to complete safety and efficacy pre-clinical testing for new biomaterials for cornea and retinal repair, enhancement of cell engraftment in the liver, and for lower limb, shoulder tendon and osteochondral applications. The role of 3 Strategic Gates to ensure the research and pre-clinical work is fully informed by experts in manufacturing, regulatory, immunology and safety considerations. Each strategic gate will be controlled by a group or panel of experts who will meet regularly to discuss the advances and prioritise technologies for clinical translation.

Planned Impact

The workplan for the next 5 years includes a spectrum of activities designed to benefit:
Academia: We will create a proactive and inclusive academic network to enhance collaboration within regenerative medicine and with allied/strategic fields across manufacturing and the cell-material interface. We anticipate immediate benefit to our ECRs and cohort of students who will have access to key training opportunities, including activities outside academic research. We will seek to position the UK as leader in regenerative medicine and will harness our international links to ensure a robust evaluation of our research, enhance staff development, and improve the translation pipeline. UKRMP2 is expected to yield scientific breakthroughs in materials science, regenerative medicine and advanced manufacturing, and to improve our understanding of the basic science of cell-material interactions.
NHS Clinicians: We have identified an unmet need for improved therapies to treat tissue degenerative diseases and injuries in eye, liver and musculoskeletal tissue. The economic burden of tissue degenerative diseases costs the NHS over £1bn/year, with musculoskeletal disease alone accounting for 8.8 million UK working days lost per year. Liver disease is the only major cause of death still increasing yearly (400% since 1970). Age related macular degeneration (AMD) currently affects more than 600k people in the UK and remains the leading cause of vision loss. By 2020, it is predicted that almost 700k people will have late-stage AMD in the UK. UKRMP2 aims to benefit patients and clinicians through the development of therapies that will improve healthcare and patient outcome across these devastating conditions. We will develop research with expectation for clinical translation in the next 5 years in the 3 areas. For the eye, we will gather pre-clinical data for the use of novel 3D biomaterials for corneal and retinal regeneration. We will lead the development of anti-fibrotic materials for reatment of liver fibrosis. In the musculoskeletal theme, we will work on early clinical adoption of shoulder tendon repair and lower limb bone repair. Critically, we will engage early with clinicians to define translational needs. Importantly, our workplan incorporates a Safety and Immunology strategic gate as a critical checkpoint to ensure product safety.
UK Industry: We will foster strong involvement with industry building upon the network generated in UKRMP1. The industrial partners in the UKRMP2 network will benefit of a platform for discussion and knowledge exchange where we will share perspectives, recognise translation and manufacturing bottlenecks, and identify skills gaps. Ultimately, the UKRMP2 Acellular Hub will create opportunities for commercial exploitation and creation of highly skilled jobs.
UK Government: In close collaboration with UKRMP and the Research Councils, we will establish communication links with the government and health agencies to increase awareness of our research, stimulate debate and inform and influence public policy in the regenerative medicine area.
Public Audience: We are passionate about communicating our work outside academia. Our dedicated outreach team will use a variety of dissemination opportunities to improve public understanding of regenerative medicine, showcase our work, open bilateral communication conduits, and educate and inspire the next generation of scientists. We will build on our extensive platform of public engagement from UKRMP1. Examples of the last 5 years include the BBSRC GB Bioscience Festival, Speakers4Schools, EPSRC, MRC and Royal Institution School Programmes and Lectures, as well as informal talks through Café Scientifique, Ask a Scientist, Meet the Expert and Pint of Science. Our award-winning Stem Cell Mountain (Oreffo, Evans, Dawson), developed with Winchester Science Centre has been taken to over 35 festivals in the last 4 years (e.g. Cheltenham, Glastonbury) and viewed by >300k people.

Publications

10 25 50
 
Title Research Data Supporting "Engineering Anisotropic Muscle Tissue Using Acoustic Cell Patterning" 
Description Raw research data supporting the publication: Armstron, JPK et al., "Engineering anisotropic muscle tissue using acoustic cell paterning", Advanced Materials, DOI: 10.1002/adma.201802649 (2018) 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
 
Title Research data supporting "Functionalisation of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks" 
Description Raw research data supporting the publication Sprott et al. "Functionalisation of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks", doi: 10.1002/adhm.201801469 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact This research data led to the publication "Functionalisation of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks", doi: 10.1002/adhm.201801469 
URL https://doi.org/10.5525/gla.researchdata.715
 
Description BMES Cell & Molecular Bioengineering Conference (Keynote Lecture), Key Largo, FL, USA, 5 January 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - 2018 MRS Fall Meeting, Boston, MA, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - 2018 MRS Spring Meeting & Exhibit, Phoenix, AZ, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - 255th ACS National Meeting and Exposition, New Orleans, LA, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - Applied Nanotechnology and Nanoscience International Conference (Plenary), Berlin, Germany 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - Beilstein Nanotechnology Symposium (Speaker & Co-organizer), Rüdesheim, Germany 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - Controlled Release Society Annual Meeting (Plenary Lecture), New York, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - Dutch Polymer Days Congress (Keynote Lecture), Lunteren, Netherlands 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - E-MRS Spring Meeting 2018 (Plenary Lecture), Strasbourg, France 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - Gordon Research Conference: Bioinspired Materials, Les Diablerets 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - Israel Materials Engineering Conference (Plenary Lecture), Dead Sea, Israel 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - Nanotexnology 2018 (Plenary), Thessaloniki, Greece 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018
 
Description Stevens talk - ORS 2018 Annual Meeting, New Orleans, LA, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Research talk given to international audience.
Year(s) Of Engagement Activity 2018