Funded Investigator– Advanced Materials and Bioengineering Research (AMBER)/Science Foundation Ireland, Industry Partnership (2018-2023)
Project title: Transition- Delivering Innovative Materials for Medical Devices
Description: Orthopaedic medicine involves treating conditions that affect the bones, soft tissue and joints. 3D printing has the potential to transform treatments in orthopaedic medicine and the orthopaedic device industry, enabling the development of personalised implants and accelerating the supply chain of device companies. TRANSITION aims to develop a hybrid device consisting of a titanium core (providing mechanical integrity) overlaid by a layer of functional tissue (engineered bone and articular cartilage) which will be particularly suited to hip and knee implants. In working towards this aim the project team will strive to advance the underpinning science and technology of metal, polymer and biological 3D printing as well as surface treatments and functional coatings. These advances will have direct benefits for improving existing implant technologies in parallel to the end goal. A key goal is to have a subset of products ready for regulatory submission and clinical studies by the end of the research programme.
Principal Investigator: Daniel Kelly
Collaborators: Prof. Mick Morris (TCD); Prof David Hoey (TCD); Prof Conor Buckley (TCD); Prof. Fergal O’Brien (Royal College of Surgeons); Prof. Eoin O'Cearbhaill (UCD); Prof. Pieter Brama (UCD); Prof. Miles Turner (DCU); Prof Garret O'Donnell (TCD); Prof Daniel Trimble (TCD); Prof Rocco Lupoi (TCD).
Funded by: Science Foundation Ireland (SFI) Spokes Award, DePuy Synthes / Johnson and Johnson
Grant ID: 17/SP/4721
Principal Investigator – Irish Research Council (IRC) - Government of Ireland Postgraduate Scholarship Scheme (2018-2022)
Project title: In silico modelling and development of physiologically relevant organ culture systems for assessment of intervertebral disc cell-based therapies
Description: Injectable cell-based therapies are being developed for the treatment of degenerated disc disease (DDD) with the aim of repopulating the nucleus pulposus and augmenting tissue repair. Prior to implantation in humans, cell therapies undergo extensive testing in petri dish experiments in the laboratory and subsequently tested in animals. However, even after demonstrating effectiveness in animals, these therapies do not appear to work to the same extent in humans. This is most likely due to the obvious differences between small animals and humans in terms of size, biomechanics, and other factors. The overall aim of this project is to use computational models to develop more realistic laboratory-based models that can be used to test the effectiveness of cell therapies thereby avoiding or reducing the need for animal testing before implantation in humans. This work will establish and define a physiologically relevant organ culture model system that could be used to screen cellular therapies at an earlier stage of development. A secondary objective is to compare the nutrient microenvironments of human and animal intervertebral discs to ascertain the clinical relevance of using live animals for assessment of cell-based regenerative therapies based on nutritional demands. If successful, this approach will have a significant impact on accelerating and advancing cellular therapies for clinical use.
Funded by: Irish Research Council.
Grant ID: GOIPG/2018/2448
Funded Investigator/Co-Investigator – Advanced Materials and Bioengineering Research (AMBER)/Science Foundation Ireland, Industry Partnership- Integra Life Sciences. (2017-2020)
Project title: A Bioactive Collagen-Based Conduit For Peripheral Nerve Repair
Description: Peripheral nerve injury remains a major clinical problem. It is estimated that 5% of multiple trauma patients have root, plexus or peripheral nerve injuries. These injuries are typically caused by transection or burns or as a result of degenerative conditions such as amyotrophic lateral sclerosis, Parkinson’s disease and multiple sclerosis. Ideally, prompt surgical intervention is required but if the injury size is >5mm or direct suturing is not possible, autografts are utilised and are currently the accepted clinical ‘gold-standard’ for treatment. However, autografts are hampered by limited availability of donor tissue and the relatively 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. Commercially available nerve guidance conduits have been developed and present promising alternatives to autografts. It is estimated that the worldwide market for peripheral nerve repair conduits is over $100 million. However, challenges arising with their use have created a major gap in the market for a drug and cell free conduit that can facilitate repair of large defects.
Funded by: Science Foundation Ireland (SFI) and Integra Life Sciences
Grant ID: 12/RC/2278
Principal Investigator – Science Foundation Ireland, Career Development Award (CDA) (2015-2020)
Project title: Intraoperative Single Stage Procedure for Intervertebral Disc Regeneration (INSPIRE)
Description: 97% of individuals over the age of 50 exhibit degeneration of the intervertebral disc (IVD). Recent investigations have shown that cell-based strategies can retard degenerative changes. However, the challenge for clinical translation remains in identifying suitable cell sources and biomaterial delivery systems to support such cells within the harsh and complex biochemical (low pH) and biomechanical environment of the disc. Intraoperative single stage cell therapies are highly attractive, avoiding the need for two hospital visits and costly in vitro cell expansion. In addition, developing injectable biomaterial systems is pivotal for minimally invasive therapeutic approaches. The overall aim of this proposal is to develop an autologous single stage therapy for intervertebral disc (IVD) regeneration. This consists of tissue harvesting from nasal septum, rapid cell isolation, development of biomimetic injectable cellular microcapsules and evaluating the proposed strategy in both ex-vivo organ culture models. If successful, the strategies outlined will create a paradigm shift in which the scientific community and clinical investigators approach early stage disc degeneration.
Collaborators: Prof. Daniel J Kelly (Trinity College Dublin), Prof. James Iatridis (Leni & Peter May Dept. of Orthopaedics, The Mount Sinai Hospital, New York, USA), Prof. Judith Hoyland and Dr. Stephen Richardson (Centre For Tissue Injury and Repair, The University of Manchester)
Funded by: Science Foundation Ireland (SFI)
Grant ID: 15/CDA/3476
Principal Investigator – Trinity College Dublin Research Capacity Building Grant- Pathfinder (2015-2016)
Project title: Towards a Single Stage Procedure for Intervertebral Disc Repair using Nasal Derived Chondrocytes (NasDisc)
Description: Autologous Disc Cell Transplantation (ADCT) has been in clinical use for the treatment of degenerated IVD in a similar manner to those currently used for cartilage repair of the knee joint. Although these therapies have made it to the clinical setting there are significant concerns regarding its effectiveness due to issues of cell leakage following cell injection into the disc, the limited tissue forming capacity of culture expanded NP cells derived from degenerated tissue and questions as to whether the number of nucleus pulposus (NP) cells that can be isolated from a degenerated disc is sufficient to meet the requirements for successful treatment. Therefore, there is a need to identify an alternative cell source for the development and clinical translation of next generation therapies for IVD regeneration. The objective of this proposal is to determine the feasibility and the subsequent tissue forming capacity of freshly isolated nasal septal derived chondrocytes on porous microcarriers to augment tissue regeneration as part of a single stage procedure.
Funded by: Research Capacity Building Grant by TCD Research Committee
Principal Investigator – EI Commercialisation Feasibility Grant (2015)
Project title: Over-the-wire Drug Delivery Device
Description: A recently developed and patented technology (Delivering drugs to desired locations within a mammal, PCT/US11/26040) at the Mayo Clinic may offer significant clinical and commercial opportunity to sustainably deliver pharmacologic agents over long periods of time. This is an Over-the-Wire Drug Delivery system that allows the placement of an anchored device on the posterior wall of the vertebral body, near the dorsal root ganglion and disc. This device could potentially provide a durable therapy and prolong the residence for short acting agents (e.g. Clonidine, dexmedetomidine, infliximab, etanercept). The objective of this project is to assess the commercial feasibility for further development and identify key tasks for continued investment.
Funded by: Enterprise Ireland
Grant ID: CF-2015-0262-Y
Principal Investigator – Irish Research Council (IRC) - Government of Ireland Postgraduate Scholarship Scheme (2014-2018)
Project title: Microencapsulation of Mesenchymal Stem Cells for Minimal Invasive Regeneration of the Intervertebral Disc
Description: The primary objective of this proposal is to develop a biomimetic hydrogel that can be combined with cells to generate microbeads formed through electrohydrodynamic (EHD) spraying for minimal invasive delivery to the IVD. The second objective is to investigate if the combination of microencapsulated mesenchymal stem cells (MSCs) in a biomimetic hydrogel will augment or improve regeneration of the nucleus pulposus in an ex vivo full organ culture model of the IVD. The third and final objective of this proposal is to investigate the combined effects of biophysical stimuli and challenging biochemical nutrient environments that normally exist in vivo on the regenerative potential of microencapsulated MSCs. If successful, the approaches outlined will create a paradigm shift in the manner in which the scientific community and clinical investigators approach biological treatment of disc degeneration. Funded by: Irish Research Council
Grant ID: GOIPG/2014/544
Principal Investigator –H2020 Support Funding (2014)
Project title: Injectable Biomimetic Hydrogels for Intervertebral Disc Regeneration (BIODISC)
Description: Support funding to facilitate the preparatory work leading to a proposal for the coordination of a research project (ERC-STG 2014) under the Horizon 2020 Programme.
Funded by: Enterprise Ireland
Principal Investigator – Irish Research Council (IRC) New Foundations Award (Mar-Nov 2014)
Project title: Nucleus Pulposus Regeneration of the Intervertebral Disc (NuGenDisc)
Description: Personal award to develop international collaborations with world-class renowned researchers, to, learn new techniques, and build on and establish new collaborations and networks.
Funded by: Irish Research Council
Principal Investigator – EI Commercialisation Grant (2012-2014)
Project title: Natural ECM Derived Injectable Microparticles for Regeneration of the Intervertebral Disc (DiscReGen)
Description: Recent evidence suggests that degeneration initiates within the central region of the disc called the nucleus pulposus (NP). The objective of this grant is to develop an injectable microparticle encapsulated Extracellular Matrix (ECM) derived from NP tissue fabricated using electrospraying technology. It is hypothesised that these microparticles will provide key biochemical cues to stimulate repair and regeneration of the disc by the patient’s own cells. This technology and approach for regeneration or repairing the intervertebral disc is highly attractive, and could be performed at an earlier stage of tissue degeneration to alleviate back pain thus reducing the number of patients requiring spinal fusion or artificial implant replacement surgery.
Collaborators: Dr. Daniel Kelly (TCD); Prof. Fergal O’Brien (RCSI); Dr. Tony Robinson (TCD); Mr. Patrick Kiely, Orthopaedic Surgeon, (SSC, Dublin).
Funded by: Enterprise Ireland.
Grant ID: CF/2012/2024
Principal Investigator – Graduate Research Engineering Programme (2012-2015)
Project title: Injectable Hydrogel Composites for Stem Cell Repair of the Nucleus Pulposus
Description:Autologous cell implantation therapies have been proposed for the treatment of degenerated IVD similar to those currently used for cartilage repair in the knee. Recent investigations have demonstrated that reimplantation of extracted nucleus pulposus (NP) cells can retard degenerative changes, and injection of autologous. NP cells have been clinically tested in humans with herniated discs. However, it is believed that the number of NP cells that can be isolated from a degenerated disc is insufficient to meet the requirements for successful treatment. As an alternative, mesenchymal stem cells (MSCs) possess significant potential and perhaps provide a more readily available and clinically feasible source of cells for IVD repair therapies. A key challenge with using MSCs is developing suitable biomaterials that can be injected into the NP compartment whilst providing the optimal biochemical and biophysical environment to facilitate differentiation. The proposed project will utilise state of the art tissue engineering and biomaterial strategies using a combination of MSCs, injectable growth factor releasing hydrogel based systems.
Funded by:Higher Education Authority (HEA). Programme for Research in Third Level Institutions (PRTLI) Cycle 5