| Project title |
Mechanobiology of mesenchymal stem cells for articular cartilage repair |
| Summary |
Mesenchymal stem cells (MSCs) have the ability to differentiate into distinctive end-stage cell types, such as those that synthesise specific mesenchymal tissues including cartilage, bone, tendon and muscle. MSCs have a number of advantages over primary chondrocytes for cartilage repair, including their ease of expansion and maintenance of phenotype. It has been shown that MSCs isolated from patients with knee OA show greater chondrogenic capability than primary chondrocytes obtained from articular cartilage biopsies from the same OA joints. However the clinical use of MSCs is restricted by insufficient knowledge of how the environment such cells will experience in vivo will influence the long-term stability of the repair tissue. The objective of this research is to provide a better understanding of how the mechanical loading experienced by MSCs or engineered tissues in vivo will influence their differentiation pathway and the quality and type of tissue they produce. Furthermore we wish to investigate whether the mechanical properties of scaffolds used to provide functional support to implanted cells can be optimised to promote and enhance chondrogenesis of the repair tissue. |
| Funding Agency |
Science Foundation Ireland |
| Programme |
President of Ireland Young Researcher Award |
| Type of Project |
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| Date from |
2008 |
| Date to |
2013 |
| Person Months |
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| Project title |
A new constitutive framework to investigate the role of mechanical forces on protein synthesis and organization during differentiation of mesenchymal progenitor cells |
| Summary |
It is believed that the mechanical environment of mesenchymal stem cells can influence their differentiation pathway. A number of different hypotheses have been proposed which describe how mechanical forces can regulate this pathway. It has been possible to test many of these ideas by encapsulating the hypothesis into an algorithm, and then conducting ‘numerical experiments’ to determine if the hypotheses on which the algorithm is based can predict realistic patterns of tissue differentiation. It is still unclear as to how the mechanical properties of tissues change during the differentiation process due to changes in protein synthesis, assembly, cross-linking, orientation etc. The hypothesis under investigation here is that mechanical forces regulate protein synthesis and organization during the differentiation of cells of the mesenchymal lineage, and hence the resulting mechanical properties of the differentiating tissue. |
| Funding Agency |
IRCSET |
| Programme |
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| Type of Project |
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| Date from |
2008 |
| Date to |
2012 |
| Person Months |
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| Project title |
Design and development of a novel device to control the fabrication, confined compression and in situ delivery of cell-seeded collagen gel scaffolds |
| Summary |
Tissue engineering strategies offer a potential solution for cartilage defect repair, however results to date have been mixed. Delivering a functional cell-seeded construct to the defect site would appear to be critical for successful cartilage repair. Recently it has been shown that plastic compression of collagen gel scaffolds leads to significant increase in the mechanical properties of the scaffold. The objective of this project is to develop a hand-held clinical device to control the gelation and levels of confined compression applied to cell-seeded collagen gels prior to implantation. By controlling the rate and magnitude of the confined compression, it is hypothesised that a gradient scaffold with depth dependant mechanical properties similar to normal articular cartilage can be fabricated and delivered directly to the defect site |
| Funding Agency |
Enterprise Ireland |
| Programme |
Proof-of-Concept |
| Type of Project |
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| Date from |
2008 |
| Date to |
2009 |
| Person Months |
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| Project title |
The influence of biophysical stimuli on tissue differentiation and matrix synthesis in vitro. |
| Summary |
Recent in vitro studies have demonstrated that both chondrogenesis and osteogeneis of bone marrow-derived mesenchymal stem cells (MSCs) can be induced using specific growth factors. Mechanical loading is known to influence the biosynthetic activity of osteoblasts and chondrocytes, however the effects of mechanical stimulation on regulating the differentiation pathway of MSCs remains unclear. The question that this proposal wishes to addresses is whether cartilage and bone like tissues can be selectively engineered using the same scaffold type and the same cell type (marrow-derived MSCs) by varying the mechanical environment of the cells. |
| Funding Agency |
Science Foundation Ireland |
| Programme |
Research Frontiers |
| Type of Project |
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| Date from |
2007 |
| Date to |
2010 |
| Person Months |
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| Project title |
Development of a method to predict which carotid plaques will rupture using Computerised Tomographic Angiography(CTA) and Duplex Ultrasound(US) with Grey-Scale Median imaging, numerical modelling, tissue testing and human serum markers |
| Summary |
Many atherosclerotic plaques form in arteries, some cause stenosis and symptoms of ischemia, whilst others lie in regions of expansive remodelling unrestricting blood flow. It is these vulnerable plaques that can be prone to sudden rupture and lead to an acute stroke or sudden death without warning. The aim of this project is therefore to identify the key characteristics normally associated with vulnerable carotid plaques, such as geometry and plaque material properties using CTA and Duplex US with GSM imaging techniques. It is then proposed to use these images to generate 3-D realistic numerical models of the vessel to estimate the stresses in the plaque under physiological loading conditions |
| Funding Agency |
Science Foundation Ireland |
| Programme |
Research Frontiers |
| Type of Project |
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| Date from |
2007 |
| Date to |
2010 |
| Person Months |
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| More Research Projects>>> |
| Buckley, C.T., Thorpe, S.D., Kelly, D.J. , Engineering of large cartilaginous constructs through the use of microchanneled hydrogels and rotational culture, Tissue Engineering |
| Maher, E., Creane, A., Sultan, S., Hynes, N., Lally, C. Kelly, D.J. , Tensile and compressive properties of fresh human carotid atherosclerotic plaques. , Journal of Biomechanics TARA - Full Text |
Boccaccio, A., Pappalettere, C., Kelly, D.J, The influence of expansion rates on mandibular distraction osteogenesis: a computational analysis, Annals of Biomedical Engineering, 35, (11), 2007, p1940 - 1960
Notes: [PMID: 17768683 ]
Url TARA - Full Text
DOI |
DJ Kelly and PJ Prendergast, Mechano-regulation of stem cell differentiation and tissue regeneration in osteochondral defects, Journal of Biomechanics, 38, (7), 2005, p1413 - 1422
Url TARA - Full Text
DOI |
Kelly, D J; Prendergast, P J; Blayney, A W, The effect of prosthesis design on vibration of the reconstructed ossicular chain: a comparative finite element analysis of four prostheses, Otology & Neurotology: Official Publication Of The American Otological Society, American Neurotology Society [And] European Academy Of Otology And Neurotology, 24, (1), 2003, p11 - 19
Notes: [PMID: 12544021 ]
Url TARA - Full Text |
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