Projects
Co-Principal Investigator – SFI Frontiers for the Future (2023 – 2028)
Project title: Engineering structurally anisotropic and mechanically functional musculoskeletal tissues by guiding the fusion, differentiation and (re)modelling of stem cell derived cartilage spheroids (22/FFP-A/11042).
Description: Regeneration of musculoskeletal tissues requires engineered grafts that mimic the heterogeneous and anisotropic structure and mechanics of the native tissue. The goal of this project is to leverage emerging biofabrication technologies to provide physical boundary conditions and spatially localised morphogens to (stem cell derived) cartilage spheroids to guide their fusion and (re)modelling to engineer truly biomimetic articular cartilage. To realise this goal, this project will build upon applicant’s extensive expertise in bioprinting and bioink development to produce a new biofabrication platform that provides physical boundaries, matrix (re)modelling factors and spatiotemporally defined patterns of growth factors to self-organizing cellular aggregates, microtissues or organoids. To demonstrate the utility of this biofabrication platform it will be used to engineer articular cartilage grafts that mimic the depth-dependant structure, composition and mechanical properties of the native tissue. The ability to bioprint such functional tissues will transform the field of orthopaedic medicine, providing grafts to biologically resurface large areas of damaged synovial joints and thereby prevent the development of osteoarthritis – a debilitating disease affecting millions of people worldwide. The impact this project will not be limited to the orthopaedic space, as it is envisioned that these new bioprinting platforms will find numerous applications in regenerative medicine.
Co-Principal Investigator: Prof Pieter Brama (University College Dublin)
Collaborators: Prof Brian Johnstone (University of Oregon)
Funded by: Science Foundation Ireland
Principal Investigator – European Research Council Proof of Concept (2023-2025)
Project title: Melt Electrowriting of Multi-layered Scaffolds for osteochondral defect repair (101137852; MEMS)
Description: An osteochondral (OC) defect is a focal area of joint damage that involves both the articular cartilage and the underlying subchondral bone. Such joint damage is strongly associated with the development of premature osteoarthritis, motivating the development of novel strategies to regenerate OC defects. 3D printing is enabling the manufacturing of geometrically complex biomaterial implants with user defined compositions and architectures, which can potentially be used as single stage, off-the-shelf scaffolds for treating complex injuries. Despite significant progress in this field, 3D printed scaffolds capable of regenerating OC defects remain elusive. This can potentially be linked to the spatial resolution possible using traditional additive manufacturing techniques. The melt electrowriting (MEW) technique has recently emerged as a novel additive manufacturing platform capable of producing polymeric scaffolds with fiber diameters in the submicron range in a highly controllable manner. We have recently developed MEW scaffolds that support superior bone regeneration compared to scaffolds produced using traditional additive manufacturing techniques. Furthermore, we have generated preliminary data demonstrating that multi-layered scaffolds generated by MEW are capable of enhancing the repair of critically sized OC defects in a pre-clinical large animal model. The MEMS project aims to further enhance the regenerative capacity of these MEW OC scaffolds by (i) optimising their architecture, and (ii) functionalizing their surface with extracellular matrix (ECM) components supportive of tissue-specific regeneration. The output of MEMS will be an off-the-shelf implant capable of directing endogenous OC defect regeneration without the need for delivering exogenous cells to the defect site.
Funded by: European Research Council.
Principal Investigator – North-South Research Programme (2022-2024)
Project title: CARTREGEN: Modelling and fabrication of microfibre reinforced composite constructs for repair and regeneration of articular cartilage
Description: Osteoarthritis (OA), a joint disease characterised by progressive loss of articular cartilage in synovial joints, is the most prevalent of all musculoskeletal pathologies, affecting millions of people (10-12% of the adult population) worldwide with tremendous individual, healthcare, and socioeconomic costs. Repair of damaged cartilage tissue via tissue engineering is one of the most promising directions to preventing the onset of OA. A particularly promising approach for articular cartilage regeneration is to seed cells within a microfibre reinforced hydrogel composite and implant this construct into the injured joint. But the progress is limited due to extensive reliance on intuitive ‘trial and error’ experimental approaches which preclude elaborate parametric investigations due to time and cost limitations. Computational modelling is a valuable tool for quickly and robustly assisting the development of such optimised composite structures. Therefore, the current project aims to develop a validated computational framework to fabricate optimised composite constructs for cartilage tissue engineering. The Queens University Belfast (QUB) team will develop the computational optimisation framework based on microscale homogenization of the composite structures and then leverage this framework to design regenerative construct biomechanical properties mimetic of the native tissue. The Trinity College Dublin (TCD). team will provide experimental input to the modelling and then fabricate the optimised structures informed by the modelling, thereby validating the computational model. The developed optimised constructs will be assessed for their cartilage regeneration potential through in vitro studies.
Collaborators: Dr Krishna Manda, Queens University Belfast.
Funded by: Higher Education Authority
Principal Investigator – European Research Council Advanced (2021-2026)
Project title: Printing spatially and temporally defined boundaries to direct the self-organization of cells and cellular aggregates to engineer functional tissues (101019344; 4D-BOUNDARIES)
Description: Regeneration of musculoskeletal tissues requires engineered grafts that mimic the heterogeneous and anisotropic structure and mechanics of the native tissue. Despite decades of research, existing regenerative strategies have failed to produce tissues mimicking this exquisite structural complexity, dramatically limiting their clinical utility. Clues to addressing this grand challenge can be found in normal tissue development, which relies upon both the self-organizing potential of stem cells as well as key physical instructions from the microenvironment to establish final tissue architectures. Recognising this, the goal of 4D-BOUNDARIES is to leverage emerging 3D bioprinting technologies to provide precise physical boundary conditions and spatially localised morphogens to self-organising cells and cellular aggregates to engineer structurally anisotropic and mechanically functional musculoskeletal tissues. To realise this goal, 4D-BOUNDARIES will build upon applicant’s extensive expertise in bioprinting and bioink development to produce two new biofabrication platforms that provide temporary guiding structures to self-organizing tissues. To demonstrate the utility of these bioprinting platforms they will be used to engineer, for the first time, patient-specific cartilage and meniscal grafts that mimic the internal and external anatomy and anisotropic mechanical properties of the native tissues. The ability to bioprint such functional tissues will transform the field of orthopaedic medicine, providing grafts to biologically resurface large areas of damaged articular cartilage and meniscus and thereby prevent the development of osteoarthritis – a debilitating disease affecting millions of people worldwide. The impact of 4D-BUNDARAIRES will not be limited to the orthopaedic space, as it is envisioned that these new bioprinting platforms will find numerous applications in tissue engineering and regenerative medicine.
Funded by: European Research Council.