Professor Conor Buckley

Summary

The proposal REGENEU aims to meet the requirements of the HORIZON-WIDERA-2021-ACCESS-03-01: Twinning Call. The main focus of this project is to increase the scientific capabilities and excellence of NEU in the field of biofiber research and development for translational application. This target is supported by European partners TLC-RT (Germany), TERM (Germany) and AMBER of the University of Dublin, Trinity College Dublin (Ireland).

Funding Agency

HORIZON-CSA

Programme

HORIZON-WIDERA-2021-ACCESS-03

Person Months

36

Summary

The global spread of obesity has been labelled a pandemic and has tripled in incidence since 1975. A major concern is the effect obesity has on low back pain (LBP), which already exceeds healthcare costs of €240 billion per year in Europe. If not addressed appropriately, with concerted efforts into appropriate treatments, the obesity pandemic and ever-growing incidence of LBP could cripple the healthcare system. The classical model or theory is that obesity influences LBP via altered distribution of forces in the spine, due to the increasing amount of abdominal fat with age. This theory is flawed for several reasons. Firstly, a notable proportion of patients presenting with LBP are young patients, reported as high as 30% of presentations. Secondly, young females store more of their fat in their thigh region. Thus, previous theories do not apply to young females and the significant proportion of LBP patients they represent. It is the premise of this proposal that the true causation of LBP in young females stems from the presence of fat tissue cells, known as adipokines, influenced by levels of oestrogen. Younger females have been shown to have higher levels of these cells than both males and elderly females. It is believed this is due to the differences in levels of oestrogen. Thus, the objective of this proposal is to ascertain the link between oestrogen, adipokines, and ultimately LBP. If successful, this work will provide new information and insights regarding the development of disc-disease and explore novel avenues for LBP treatment strategies in young females.

Funding Agency

Irish Research Council (IRC)

Programme

Government of Ireland Postgraduate Scholarship

Person Months

48

Summary

Peripheral nerve injury remains a major clinical problem. Autografts are the current 'gold standard' but are hampered by limited availability of donor tissue with poor prognosis for functional recovery at both the donor and recipient sites. As a result, new approaches are currently being investigated to develop artificial nerve grafts which mimic the properties of autologous grafts. Additive manufacturing (AM) techniques such as 3D bioprinting (3DBP) offers exciting new opportunities and horizons to engineer nerve guidance conduits (NGCs) that more closely match the composition and structure of native nerve tissue. These approaches facilitate precise control over the external and internal microarchitecture geometry. In the context of developing engineered nerve tissue AM offers the added ability to incorporate drug delivery systems with tailorable spatial and temporal release profiles of individual drugs. Similarly, following peripheral nerve injury, the transfer of electrical signals across a damaged nerve is inhibited, resulting in degeneration of the distal nerve segment. Printing offers the potential to create specific geometries with defined micropatterns as well as incorporating electroconductive biomaterials to provide direct electrical activation to enhance tissue repair, enhance cell function and alignment. Applying electrical stimuli may enhance the regeneration as it is known that inhibition of electrical signalling can impede normal tissue function. Using bioinks derived from native nerve as a biomaterial platform developed in the Buckley lab for peripheral nerve tissue regeneration, this project proposes to enhance regenerative capacity of NGCs through the incorporation of electroconductive materials from partner labs in AMBER (e.g. graphene, silver nanowires, polypyrrole). Such a conductive biomaterial could thus provide direct electrical activation of isolated regions while also providing a scaffolding template to enhance the tissue repair process. Following optimisation of the fabrication/printing process, in vitro biocompatibility of the biofabricated NGCs and the response of cells to electrical stimuli will be assessed using in vitro methods prior to pre-clinical assessment.

Funding Agency

AMBER/SFI

Project Type

Research

Person Months

48

Summary

Common European Masters in Biomedical Engineering (CEMACUBE) received the European Institute of Innovation and Technology (EIT) label, which was successfully awarded in 2019. The EIT is a European innovation body inspiring a new generation of entrepreneurs and innovators in Europe. This initiative links with the TCD MSc in Bioengineering with specialisation in Tissue Engineering.

Funding Agency

EIT Health

Programme

EIT Label

Project Type

Education

Person Months

12

Summary

Lower back pain is a global epidemiological and socioeconomic problem. Biomaterial and cell-based therapies have been pursued for the treatment of degenerated intervertebral disc (IVD), with a number of clinical trials underway. However, the degenerated intervertebral disc has a distinct environment (e.g. altered oxygen, glucose, acidity, inflammatory cytokine levels) that is unique to an individual (i.e. patient-specific) and will ultimately determine the likelihood and rate at which regeneration can occur. A "one size fits all" approach will lead to the failure to demonstrate efficacy of advanced therapies, as they are not being designed or personalised for individual patients. This proposal envisions a future whereby advanced gene activated cell therapies are personalised (targeting regeneration or modulating inflammation) to treat back pain based on knowing the individuals unique disc microenvironment. This will be achieved through profiling of individual patient disc microenvironmental factors, with in vitro screening and in silico modelling to design cell therapies and predict regeneration outcomes (Aim 1) combined with the development of tailored functionalised gene activated biomaterials (Aim 2), to enhance matrix formation and modulate the inflammatory processes (Aim 3). Gene-based therapy offers several advantages over direct delivery of proteins or small molecules, among them the possibility of sustained efficacy and endogenous synthesis of growth factors or suppression of inflammatory factors and pathways. The platform technology (personalised gene activated biomaterials to regulate regeneration and inflammation) and knowledge (tailoring cell therapies to suit patient-specific microenvironments) generated through this research are beyond the current state-of-the-art and will provide a significant transformative scientific and clinical step change opening new horizons in minimally-invasive therapeutic strategies.

Funding Agency

European Research Council

Programme

Consolidator Award (CoG)

Project Type

Applied Research

Person Months

60