ISTM

Sarah's research focus of orthopaedic tissue engineering is multidisciplinary and she works at the interface of engineering and medicine by being employed alternately between both engineering and health faculties.

Her research training began at the University of Liverpool with a B.Eng. degree in Clinical Engineering with Materials Science (1993-1996). In 1999 she completed a Ph.D. in Clinical Engineering (also at Liverpool University) within the Faculty of Health. Her EPSRC-funded CASE Ph.D. (with Giltech Ltd., Scotland) focussed on researching different medical applications of a novel degradable phosphate based glass. One of these applications was ligament and tendon tissue engineering and she continued these studies further and specialised in orthopaedic tissue engineering.

In 2000 Sarah began a 2year postdoctoral fellowship within the Woodruff School of Mechanical Engineering at Georgia Institute of Technology, Atlanta, USA, optimising a bioreactor system that allowed cultivation and mechanical force application of/to functional tissue engineered bone constructs. In 2002 she returned to the UK for a second postdoctoral research position in the Institute for Science & Technology in Medicine at Keele.

Sarah obtained a lectureship in orthopaedic tissue engineering in 2004 in Keele's School of Medicine and built up her research group to five members through a range of large research grants from Research Councils and charities.

From 2007 to 2010 Sarah was Co-ordinator for the M.Sc. in Cell and Tissue Engineering programme hosted in ISTM at Keele.

In 2010 Sarah moved to a Readership at the nearby Manchester School of Materials but retains an honorary Keele research position and strong collaborative links with ISTM through ongoing and new research projects.

ISTM Research theme: 1. Bioengineering & Therapeutics

My current interests are in orthopaedic tissue engineering. I am interested in the effect of chemical and mechanical stimuli on articular chondrocytes, osteoblasts, osteo-progenitor cells and stem cells. Bone and cartilage tissue engineering are typically considered independent problems, requiring different approaches to cultivate implantable cellular constructs in vitro and regenerate biomechanically functional tissues in vivo. However, the close association of bone and cartilage during development and skeletal tissue repair suggests that an integrated approach to engineering osteochondral tissues may be advantageous. Recent improvements in our understanding of stem cell biology offer the opportunity to test novel tissue-engineering strategies to improve wound healing of osteochondral defects associated with osteoarthritis or joint trauma. While cartilage-like constructs may be readily created in vitro, the functional integration of such constructs in vivo is a critical barrier that must be addressed in order to achieve long-term efficacy using this approach. I am interested in researching tissue engineering of bone, cartilage and osteochondral defects using in vitro differentiated stem cells. I am currently performing experiments in developing novel bioreactors for the growth of such tissue-engineered constructs. Using the SCANCO microCT40 system we have at ISTM, it is possible to quantitatively evaluate the production of mineralised matrix on tissue-engineered constructs.

Current projects include the following:

• Influence of mechanical force application on human mesenchymal stem cell differentiation
• Design of a novel co-culture bioreactor for osteochondral tissue-engineered plugs
• Use of statins for influencing osteoblast proliferation and differentiation
• Validation of fluid flow characteristics in a Perfusion Bioreactor (for Bone Tissue Growth and cell seeding optimisation)

Figure 1: MicroCT images of mineralized matrix produced by rat stromal cells seeded onto porous gelatin scaffolds and culture for 6 weeks in vitro (left: top view, right: side view).

We are currently applying mechanical forces directly to cells using magnetic particle technology. This involves attaching a magnetic particle (varying in size from nanometres to microns) to a cell membrane via a specific receptor that is determined by the protein that the particle is coated with. When an oscillating external magnetic feld is applied, the magnetic particle responds by moving in relation to the field thus applying a stretch/torque on the cell membrane. We have applied forces directly to the cells in the order of 10 piconewtons in this way and have shown osteoblasts to respond by upregulated bone related gene expression and producing mineralised matrix at an earlier time point in comparison to controls performed.

Figure 2: Confocal microscopy image showing fluorescent nuclei and actin filament staining of osteoblasts plus adhered magnetic particles (4.5 micron diameter particles) (location indicated by pink dots).

Selected Publications

Refereed Journal Publications

1. GRIFFITHS, S.L. and CARTMELL, S.H. (2007) Use of Statins for Enhancing Bone Tissue Engineered Grafts, European Journal of Plastic Surgery, pp. in press.
2. ENIWUMIDE, J.O., YUAN, H., CARTMELL, S.H., MEIJER, G.J. and BRUIJN, J.D.D. (2007) Ectopic bone formation in bone marrow stem cell seeded calcium phosphate scaffolds as compared to autograft and (cell seeded) allograft, European Cells and Materials, 14, pp. 30-39.
3. Charles Cranfield, Ze’ev Bomzon, Daniel Day, Min Gu, Sarah Cartmell (2006) “Mechanical Strains Induced in Osteoblasts be use of Focused Femntosecond Laser Targeting” International Journal of Biomedical Imaging Article ID 21304 pages 1-6
4. J. Dobson, S.H. Cartmell, A. Keramane, A.J. El Haj (2006) “A Novel Magnetic Force Mechanical Conditioning Bioreactor for Tissue Engineering, Stem Cell Conditioning and Dynamic In Vitro Screening”I IEEE Transcations on NanoBioscience 5(3) September 173-177
5. Gemma Jones and Sarah H. Cartmell  (2006) “Optimisation of Cell Seeding Efficiencies on a 3D Gelatin Scaffold for Bone Tissue Engineering”; Journal of Applied Biomaterials and Biomechanics 4  172-180
6. Sarah Cartmell (2006) “Statins and their Benefits for Growing Bone Tissue”; Midlands Medicine 24(1) (October 2006) 28-29
7. John J.A, Barry, Marta Silva, Sarah H. Cartmell, Robert E. Guldberg, Colin A. Scotchford, Steven Howdle (2006)  “Porous Methacrylate Tissue Engineering Scaffolds: Using Carbon Dioxide to Control Porosity and Interconnectivity”; Journal of Materials Science 41(13) July (2006) 4197-4204
8. Sarah H Cartmell, Ahmed Keramane, Glen R Kirkham, Sarah B Verschueren, Julia L Magnay, Alicia J El Haj, Jon Dobson (2005) “Use of Magnetic Particles to Apply Mechanical Forces for Bone Tissue Engineering Purposes”; Journal of Physics 17  77-80
9. Sarah Cartmell, Julia Magnay, Alicia El Haj, Jon Dobson (2005) “A Novel Mechanical Conditioning Regime for Tissue Engineered Constructs”; International Journal of Experimental Pathology 86(3) June (2005) A38
10. Sarah Cartmell, Kimberly Huynh, Angela Lin, Srinidhi Nagaraja, and Robert Guldberg (2004) “Quantitative Microcomputed Tomography Analysis Of Mineralization Within 3D Scaffolds In Vitro”; Journal of Biomedical Materials Research Part A 69A(1)  97-104
11. Sarah H. Cartmell, Blaise D. Porter, Andres J. Garcia, Robert E. Guldberg (2003) “Effects of Media Perfusion Rate on Cell Seeded 3D Bone Constructs In Vitro”; Tissue Engineering 9(6) 1197- 1203
12. Angela S.P. Lin, Thomas H. Barrows, Sarah H. Cartmell, Robert E. Guldberg (2003) “Microarchitectural and Mechanical Characterization of Oriented Porous Polymer Scaffolds”;  Biomaterials  24(3) 481-9
13. Sarah Cartmell, Julia Magnay, Jon Dobson, Alicia El Haj (2003) “Effects of Mechanical Force Application on 3D Bone Tissue Engineered Constructs Using Magnetic Microparticles”; European Cells and Materials 6(Suppl. 2) 7
14. Sarah H. Cartmell, Jon Dobson, Sarah B. Verschueren, Alicia J. El Haj (2002) “Development of Magnetic Particle Techniques for Long Term Culture of Bone Cells With Intermittent Mechanical Activation”; IEEE Transactions on NanoBioscience 1 (2002) 92-97
15. S.H.Cartmell, J.Dobson, S.Verschueren, S.Hughes, A. El Haj (2002) “Mechanical Conditioning of Bone Cells In Vitro Using Magnetic Microparticle Technology”; European Cells and Materials 4(2) Dec (2002) 130-131
16. SH Cartmell, BD Porter, RE Guldberg  (2000) “Design of a 3-D Perfused Cell Culture System To Evaluate Bone Regeneration Technologies”; Tissue Engineering 6  665
17. BD Porter, SH Cartmell, RE Guldberg (2000) “Passage Dependancy of Rat Calverial Cells on Mineralized Nodule Production”; Tissue Engineering 6  696
18. Sarah H. Cartmell, Patrick J. Doherty, John A. Hunt, David M. Healy, Thomas Gilchrist (1998) “Soft Tissue Response to Glycerol-Suspended Controlled Release Glass Particulate”; Journal of Materials Science: Materials in Medicine 9 (1998) 773-777
19. Sarah H. Cartmell, Patrick J. Doherty, Nicholas P. Rhodes, John A. Hunt, David M. Healy, Thomas Gilchrist (1998) “Haemocompatibility of Controlled Release Glass”; Journal of Materials Science: Materials in Medicine 9 (1998) 1-7
    

Book Chapters

1. "Tissue Engineered Bone Grafts" In Applications of Cell Immobilisation Biotechnology. Pankaj Sharma, Sarah Cartmell, Alicia El Haj. Editors: Professor Viktor Nedovic and Professor Ronnie Willaert Kluwer Academic Publishers (2005) ISBN 1-4020-3229-3
2. "Mechanical Bioreactors for Tissue Engineering" In Bioreactors for Tissue Engineering Sarah H. Cartmell, Alicia J. El Haj. Editors Dr Julian B Chaudhuri and Dr Mohamed Al Rubeai Kluwer Academic Publishers (2006)
3. “Genes and Proteins Involved in the Regulation of Osteogenesis” In Expertissues E-Book: Topics in Tissue Engineering, Volume 3 (http://www.oulu.fi/spareparts/ebook_topics_in_t_e_vol3/index.html) Glen Kirkham and Sarah H. Cartmell. Editors Professor Nureddin Ashammakhi, Dr Rui Reis, Dr Emo Chiellini (submitted).

Research Funding

Biotechnology & Biological Sciences Research Council (BBSRC)
£793,818 (£509,341 Keele, £284,477 Sheffield Hallam) Research grant
‘Optimisation of Perfusion Bioreactor for Bone Tissue Growth’
(in collaboration with Professor Chris Care and Dr Ian Halliday, Dept. of Mathematics, Sheffield Hallam University) (June 2008 – May 2011)

Engineering & Physical Sciences Research Council (EPSRC) ‘Doctoral Training Award’
~£700,000 (~£240,000 to Keele)
Dr Cartmell is named key staff on this multidisciplinary grant as potential supervisor to PhD students (approx 10 students expected to be funded in this scheme – 3/4 based at Keele University). Collaborative grant with University of Loughborough and University of Nottingham. Professor Alicia El Haj, Professor James Richardson and Professor Nureddin Ashammakhi lead PIs on this grant.

Royal Society
£15,000 – Research grant ‘Development of a Tissue Engineered Ligament using Novel Biomaterials in a Dynamic Environment’, November 2006

Pfizer UK
£6,000 – Industrial collaboration, consumable funding support for project entitled ‘Physiological Side Effect Analysis of Atorvastatin – Stabilisation of Atherosclerotic Plaques’ (August 2006 - July 2007)

EMPA, St Gallen, Switzerland
~£45,000 (100,000CHF)  - In collaboration with Dr Manfred Zinn, ‘Use of polyhydroxylalkonate fibres for tendon tissue engineering’ (August 2006 – July 2008). 

Biotechnology & Biological Sciences Research Council (BBSRC)
£14,600 – Modular Training for Industry Programme - pump priming grant for set up of 2day workshops on bioreactors for tissue engineering (June 2006).

Biotechnology & Biological Sciences Research Council (BBSRC) CASE PhD studentship
~£60,000 – CASE award in collaboration with Giltech Ltd., Ayr, Scotland
‘Tissue Engineering of Anterior Cruciate Ligament using Degradable Phosphate Based Glass Fibres’ (October 2006 – September 2009)  

European 6th Framework Programme: Integrated Project 'MYJOINT'
2.03million Euro in total - one of eight partners (co-ordinated by University of Kiel, Germany) (August 2006 - 2009) 

Biotechnology & Biological Sciences Research Council (BBSRC)
£269,848 – New Investigator Award – ‘Influence of Mechanical Force Application on Human Mesenchymal Stem Cell Differentiation’ (January 2006 – December 2008) 

Private Local Charity
£200,000 – Co-investigator with Dr Nikki Goodstone, Keele University. PhD studentship ‘Using Tissue Engineering Strategies for the relief of Osteoarthritis’ (November 2005 – October 2008) 

 European 6th Framework Programme: Network of Excellence ‘EXPERTISSUES’
~£180,000  - named investigator (Professor Alicia El Haj - PI) (co-ordinated by University of Minho) (October 2004 – October 2008)

Australian Research Council
~£2,385 (5,850 Australian Dollars) in collaboration with Dr Charles Cranfield, Centre for MicroPhotonics, Swinburne University of Technology, Australia from the ‘Fluorescence Applications in Biotechnology and Life Sciences’ (FABS) Network, to fund travel costs for a project entitled ‘Nonlinear Optical Techniques for Activation and Imaging of Bone Cells’ (August 2005 – December 2005)

Australian Research Council
~£710 (1,560 Australian Dollars) in collaboration with Dr Charles Cranfield, Centre for MicroPhotonics, Swinburne University of Technology, Australia from the ‘Fluorescence Applications in Biotechnology and Life Sciences’ (FABS) Network, to fund consumable costs for a project entitled ‘Nonlinear Optical Techniques for Activation and Imaging of Bone Cells’ (August 2005 – December 2005)

University Hospital of North Staffordshire R&D Consortium and Keele University School of Medicine
£15,000 - Funding for consumables for PhD student project (Glen Kirkham, Keele University), March 2004 – September 2006

North Staffordshire Medical Institute
£250 - Travel grant to attend European Society of Biomaterials Conference, Barcelona, Spain 2002

The Wellcome Trust
£600 - Travel grant to attend International Smith and Nephew Tissue Engineering Conference, Atlanta GA 2002

Royal Academy of Engineering
£400 - Travel grant to attend European Society of Biomaterials Conference, Barcelona, Spain 2002

Royal Academy of Engineering
£400 - Travel grant for working visit to the Dept. of Biomedical Science, Universita Tor Vegata, Rome, June 1998

Research team members past and present:

Nesta Hughes                           Postdoctoral Research Fellow ‘Relief of Osteoarthritis Using Tissue Engineering Strategies’ at ISTM, Keele University. Dr Cartmell is joint lead supervisor with Dr Nikki Kuiper. March 2008- February 2010.

John Glossop                            Postdoctoral research fellow at ISTM, Keele University. ‘Influence of Mechanical Force Application on Human Mesenchymal Stem Cell Differentiation’. Dr Cartmell is lead and sole supervisor. Feb 2006 – Jan 2009.

Zhang Tang                              Postdoctoral research fellow at ISTM, Keele University. ‘Scaffold Fabrication for MY JOINT’. Professor Nureddin Ashammakhi is lead supervisor with co-supervisors Professor Alicia El Haj and Dr Sarah Cartmell. June 2007 - May 2009.

Sarah Rathbone                        Ph.D. student at ISTM, Keele University. ‘Tissue Engineering of Anterior Cruciate Ligament using Degradable Phosphate Based Glass Fibres’. Dr Cartmell is lead and sole supervisor. Oct 2006 – Sept 2009.

Sarah Griffiths                           Ph.D. student at ISTM, Keele University. ‘Use of Statins for Bone Tissue Engineering’. Dr Cartmell is lead and sole supervisor. Oct 2005 – Sept 2008.

Gemma Jones                           Ph.D. student at ISTM, Keele University. ‘An Investigation of Extracellular Matrix and Scaffold Turnover During Orthopaedic Tissue Engineering’. Dr Cartmell is lead supervisor, co-supervisor is Professor Alicia El Haj. Jan 2005 – June 2008.

Glen Kirkham                           Ph.D. student at ISTM, Keele University (passed with minor corrections - final corrected thesis submitted September 2007). Thesis title “Applying forces to human osteoblasts and mesenchymal stem cells using a novel magnetic particle technique”. Dr Cartmell was lead supervisor with Professor Jon Dobson as co-supervisor. Oct 2003 – Sept 2007

Sarah Thurstan                         M.Sc. student in cell and tissue engineering graduate course at Keele University for 6 month research project. ‘Polarization of Hydroxyapatite Scaffolds – Influence on osteoprogenitor cell seeding, migration and extracellular matrix production’ in collaboration with Dr Irene Turner and Dr Jon Gittings at Department of Materials Science, Bath University. Dr Cartmell was lead and sole supervisor. Apr – Sept 2007

Sarah Griffiths                           M.Sc. student  in cell and tissue engineering graduate course at Keele University for 6 month research project. Student received a distinction in this masters course. ‘Use of Statins for Enhanced Bone Tissue Engineering Constructs’. Dr Cartmell was lead and sole supervisor. Apr – Sept 2005.

Gemma Jones                           M.Sc. student  in cell and tissue engineering graduate course at Keele University for 6 month research project. ‘Optimisation of Cell Seeding Efficiencies on 3D Scaffolds for Bone Tissue Engineering’. Dr Cartmell was lead and sole supervisor. Apr – Oct 2004

Onyi Irrecheckwu                     2nd year Ph.D. student from Georgia Institute of Technology, Atlanta for 3 month internship at ISTM, Keele University. ‘Use of Magnetic Particle Technology to Apply Forces to Chondrocytes’. Dr Cartmell was lead supervisor with Professor Alicia El Haj as co-supervisor. June - Sept 2003.

Sarah Verschueren                   M.Sc. student in medical physics graduate course at Keele University for 6 month research project. Student received a distinction in this masters course. ‘The Use of Magnetic Particle Technology for the Mechanical Conditioning of Bone Cells’. Dr Cartmell was lead supervisor with Professors Alicia El Haj and Jon Dobson. April - Sept 2002

Kimberly Huynh                       Undergraduate Research Scholar (URS)  at Georgia Institute of Technology. Techniques taught such as sterile tissue culture, PCR, SEM and confocal microscopy. ‘Micro Computed Tomography Evaluation of 3D Stromal Cell Seeded PLDL and Demineralised Bone Scaffold Constructs’. Dr Cartmell was lead and sole supervisor. Jan - Dec 2001.

Onyi Irrecheckwu                    Second year Ph.D. student from Georgia Institute of Technology, Atlanta for 3 month internship at ISTM, Keele University. ‘Use of Magnetic Particle Technology to Apply Forces to Chondrocytes’. June - Sept 2003.

Sarah Verschueren                  M.Sc. student in medical physics graduate course at Keele University for 6 month research project. Student received a distinction in this masters course. ‘The Use of Magnetic Particle Technology for the Mechanical Conditioning of Bone Cells’. April-Sept 2002.

Kimberly Huynh                        Undergraduate Research Scholar (URS) at Georgia Institute of Technology. Techniques taught such as sterile tissue culture, PCR, SEM and confocal microscopy. ‘Micro Computed Tomography Evaluation of 3D Stromal Cell Seeded PLDL and Demineralised Bone Scaffold Constructs’. Jan. 2001-Dec. 2001.