Biotextiles for ligament repair using biofunctionalisation to aid regeneration

Lead Research Organisation: University of Manchester
Department Name: Materials

Abstract

The project will be integrated into the UKRMP Acellular approaches for therapeutic delivery Hub, a collaboration between Manchester, Nottingham, Imperial, Southampton, Keele and others.
http://www.ukrmp.org.uk/hubs/

Anterior cruciate ligament (ACL) ruptures are a common problem and occur mostly as a result of sports injuries. Around 200,000 ACL ruptures per year occur in the United States and it is estimated that more than 100,000 ACL repairs are performed annually in the United States.

Such ruptures can subsequently lead to other, serious degenerative joint diseases and for this reason it is important to treat and tackle ACL injuries efficiently and effectively. The current gold standard for ACL repair involves the use of patellar tendon autografts; this treatment has many limitations including: donor site morbidity and more importantly the inability of the graft to fully integrate with the bone tunnel site (area often referred to as the enthesis). High failure rates often occur particularly at this enthesis site subsequently leading to patient revisits for further improved surgeries. Hence, an intervention is required which could be coupled with the current gold standard method to act as a dual technology, which could provide more robust graft integration.

Some research has been performed in developing alternative grafts fabricated from synthetic FDA approved materials including Poly-e-Caprolactone (PCL) and PET with the hope to manufacture tissue-engineered grafts that would provide the required mechanical properties. However, limitations associated with such constructs include their lack of bio-interaction, lack of functional neo-matrix lay down and remodeling, leading to failure at the enthesis site. Therefore, the problem of graft failure (autograft or synthetic) at the enthesis site is yet to be fully resolved. For this reason this study aims to improve graft integration at the enthesis site through improved healing rate.

In this case, we aim to develop a synthetic graft, which is able to precisely mimic the nano-and micro- architecture of native tissue ACL extracellular matrix along with the appropriate mechanical properties and degradation rate. Working in collaboration with Professor Eithne Comerford (University of Liverpool), we aim to identify key extracellular matrix (ECM) protein fragments within the different regions of the ACL (particularly the enthesis) and functionalise these onto the synthetic graft. We have identified fibrillin-1 as a starting point and preliminary results have shown significantly more rapid attachment and alignment along the electrospun fibres with fibrillin present. Further molecules have been identified and will be explored along with signalling pathways.
Cell behavior will be assessed in terms of cell viability, morphology, proliferation, differentiation, intra- and extracellular signalling pathways and neo-matrix secretion. These will be validated and identified using via immunocytochemistry, ELISA, RT-PCR and histology.

Additionally the electrospun system could be used as a platform technology for other ligaments and also tendon repair.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509565/1 01/10/2016 30/09/2021
1735234 Studentship EP/N509565/1 16/09/2016 31/03/2021 Zara Smith
 
Description Biofunctionalisation of aligned polymer scaffolds with protein fragments may improve ligament cell responses to synthetic materials, which may in the future be an alternative treatment for ligament tears/ruptures.
Exploitation Route Outcomes may provide novel pathways for the investigation of integral ECM proteins effect on ligament repair.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://www.ecmconferences.org/abstracts/2018/Collection4/c4.html
 
Description Henry Royce Institute Research Grant
Amount £5,663 (GBP)
Organisation Henry Royce Institute 
Sector Academic/University
Country United Kingdom
Start 08/2019 
End 09/2019
 
Description President's Doctoral Scholars Award
Amount £3,000 (GBP)
Organisation University of Manchester 
Sector Academic/University
Country United Kingdom
Start 09/2016 
End 02/2020
 
Description President's Doctoral Scholars Travel Award
Amount £500 (GBP)
Organisation University of Manchester 
Sector Academic/University
Country United Kingdom
Start 09/2018 
End 09/2018
 
Description Collaboration with Liverpool Musculoskeletal Biobank - human ACL cells 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution We are using the tissue to digest and remove the cells for experimentation relevant to the biobank and associated academic's interests. They will have access to all our work and data and we will be providing them with regular updates.
Collaborator Contribution In turn, the Liverpool Musculoskeletal Biobank (LMB) will be providing us with human anterior cruciate ligament tissue and advice for the continuing experimentation.
Impact No outputs or outcomes as of yet.
Start Year 2019
 
Description Collaboration with Liverpool University - Canine CL cells 
Organisation University of Liverpool
Department Institute of Ageing and Chronic Disease
Country United Kingdom 
Sector Academic/University 
PI Contribution Though we have not had any contribution in terms of training, we will be including the research team at Liverpool University as authors in any papers we publish and we will be furthering work which is of interest to their research focus as a whole.
Collaborator Contribution They have provided primary canine cells, which have been used in the first two parts of the project, I have worked with them at Liverpool University, performing experiments with post doctoral staff.
Impact Presentations at two conferences, one European and one national. Posters presented at two conferences, one European and one national. We are also currently writing a paper on the data gathered thus far and intend to publish in the very near future.
Start Year 2016
 
Description Lecture for a girl's STEM visit 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Approximately 50 female students attended a lecture where I discussed research and the area in which I perform my research. I have discussed parts of my research with the students and explained to them the importance of ongoing research in my immediate area.
Year(s) Of Engagement Activity 2018
URL http://www.mub.eps.manchester.ac.uk/science-engineering/2019/02/14/dragonfly-day-women-can-do-anythi...
 
Description Postgraduate summer research showcase 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact A poster fair regarding postgraduate student's research projects. Posters are hung and discussed and general public, staff and students are welcomed to discuss research going on within the university. Visitors reported fascination with the work and interest in the potential long-term development of the research.
Year(s) Of Engagement Activity 2018
URL http://www.psrs.manchester.ac.uk/
 
Description STEM Fair Stand at Manchester Cricket Grounds 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact A stand was made for the interest of 4 years groups of 11 - 15 year old students at the Old Trafford cricket grounds centre in Manchester. Students could take part in small stand-suitable activities and learn about biomaterials and talk about the research concerning this area.
Teachers reported extreme interest in the areas discussed and have requested further events for the purpose of introducing students to new and fascinating STEM areas.
Year(s) Of Engagement Activity 2018
 
Description STEM for girls workshops held at the University of Manchester 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 45 female pupils from secondary schools in the greater Manchester area attended outreach events for widening participation. We discussed and performed experiments relevant to the area I am conducting my project work. The school reported that they very much enjoyed the workshop and that it had sparked a lot of interest from the attending pupils.
Year(s) Of Engagement Activity 2018,2019
URL http://www.mub.eps.manchester.ac.uk/science-engineering/2019/02/14/dragonfly-day-women-can-do-anythi...
 
Description School visit to talk about STEM subjects 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Visit made to a school in the greater Manchester area for 5 workshops spread across the day. In these workshop sessions, I interacted with boy male and female pupils of ages between 12 and 15 and introduced them to my research area and the work we do. I also introduced them to my research and explained why it was important for furthering orthopedic medicine. We performed a large practical experiment where the students discovered how to make simple biomaterials of their own.
Year(s) Of Engagement Activity 2018