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| Engineering materials at the interface with the medical and natural sciences |
Bio-responsive nanomaterials are of growing importance with potential applications including drug delivery, diagnostics and tissue engineering. Research in regenerative medicine within the group includes the directed differentiation of stem cells, the design of novel bioactive scaffolds and new approaches towards tissue regeneration. We have developed novel approaches to tissue engineering that are likely to prove very powerful in the engineering of large quantities of human mature bone for autologous transplantation as well as other vital organs such as liver and pancreas, which have proven elusive with other approaches. This has led to moves to commercialise the technology and set-up a clinical trial for bone regeneration in humans. In the field of nanotechnology the group has current research efforts in exploiting specific biomolecular recognition and self-assembly mechanisms to create new dynamic nano-materials, biosensors and drug delivery systems.
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Bioactive Scaffolds and Tissue Engineering |
The highly interdisciplinary field of Tissue Engineering (TE) is benefiting from advances in the design of bio-responsive nanomaterials. TE involves the development of artificial scaffold structures on which new cells are encouraged to grow. The ability to control topography and chemistry at the nanoscale offers exciting possibilities for stimulating growth of new tissue through the development of novel nanostructured scaffolds that mimic the nanostructure of the tissues in the body. We are developing bioactive nanomaterials, nanocomposites and hydrogels for tissue regeneration. We have also developed new approaches to regenerate organs using an in vivo tissue engineering approach.
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Engineering the Cell-Material Interface |
Cells are inherently sensitive to local mesoscale, microscale, and nanoscale patterns of chemistry and topography. We are developing approaches to control cell behavior through the nanoscale engineering of materials surfaces including monolayer protected metal nanoparticles, nanotubes and other nanotopographies/nanochemistries. Far-reaching implications are emerging for applications including medical implants, cell supports, and materials that can be used as instructive three-dimensional environments for tissue regeneration.
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Live Cell Micro-Raman Spectroscopy |
Raman microspectroscopy shows tremendous promise for the analysis of biological processes within living cells, such as cell cycle dynamics, cell differentiation and cell death. Unlike conventional biological assays, laser-based Raman spectroscopy enables rapid and non-invasive biochemical analysis of cells in the absence of fixatives or labels. The low Raman signal of cell culture buffer/media permits the rapid monitoring of living cells growing under standard cell culture conditions. The Raman spectrum of a cell is a biochemical 'fingerprint', containing molecular-level information about all biopolymers contained within the cell. The high information content of Raman spectra can be used to characterize the distribution of multiple cellular components, and to study the dynamics of subcellular reactions, with excellent spatial resolution. We are applying live cell Raman spectroscopy and multivariate analytical techniques to study cell differentiation/tissue engineering, heart valve calcification and toxicological studies.
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Nanomaterials for Enzyme Sensing and Drug Delivery |
DNA-, protein- or peptide-functionalised nanoparticle (NP) aggregates are particularly useful systems since triggered changes in their aggregation states may be readily monitored. For example, dispersion of gold NP assemblies results in a blue-to-red shift in the visible spectrum. The ability to dynamically assemble and dis-assemble such structures under physiologically accessible environmental conditions, as triggered for example by changes in pH would be valuable for the generation of novel tunable and/or switchable materials. We have exploited the coiled-coil peptide based assembly of gold NPs and demonstrated that the system can be controlled under mild conditions (near-neutral pH and ambient temperature). Conceptually novel approaches to real-time monitoring of protease and kinase enzyme action using modular peptide functionalized gold NPs and quantum dots are ongoing as is the development of new drug delivery systems.
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| Recent selected references |
1. Swain, RJ, Kemp, SJ, Goldstraw, P, Tetley, TD, Stevens, MM, Spectral Monitoring of Surfactant Clearance during Alveolar Epithelial Type II Cell Differentiation, BIOPHYSICAL JOURNAL, 2008, Vol: 95, Issue 12, Pages: 5978 - 5987.
2. Laromaine, A, Koh, LL, Murugesan, M, Ulijn, RV, Stevens, MM. Protease-triggered dispersion of nanoparticle assemblies, J AM CHEM SOC, 2007, Vol: 129, Pages: 4156 - 4157.
3. Stevens, MM, George, JH, Exploring and engineering the cell surface interface, SCIENCE, 2005, Vol: 310, Pages: 1135 - 1138.
4. Stevens, MM, Marini, RP, Schaefer, D, Aronson, J, Langer, R, Shastri, VP. In vivo engineering of organs: The bone bioreactorPROC NATL ACAD SCI USA, 2005, Vol: 102, Pages: 11450 - 11455 and report in SCIENCE, 2005, Vol: 309, Page 683.
5. Ghadiali, JE, Stevens, MM. Enzyme-Responsive Nanoparticle Systems ADVANCED MATERIALS, 2008, Vol: 20, Issue 22, Pages: 4359 - 4363.
6. Place, ES, Evans, ND, Stevens, MM. Complexity in biomaterials for tissue engineering. NAT MATER , 2009, Vol: 8, Pages: 457 - 470.
7. Gentleman, E, Swain, RJ, Evans, ND, Boonrungsiman, S, Jell, G, Ball, MD, Shean, TAV, Oyen, ML, Porter, A, Stevens, MM. Comparative materials differences revealed in engineered bone as a function of cell-specific differentiation. NAT MATER , 2009, Vol: 8 , Pages: 763 - 770
For more complete list see http://www3.imperial.ac.uk/people/m.stevens/publications.
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