M.V. Sefton

 

Contact the Professor at:

michael.sefton@utoronto.ca

phone: 416-978-3088
fax: 416-978-4317

LAB: Donnelly Centre for Cellular and Biomolecular Research, Fourth Floor; 416-978-6518
OFFICE: Donnelly Centre for Cellular and Biomolecular Research, Room 406, 160 College Street
MAILING ADDRESS: Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Suite 407, Toronto, Ontario, Canada M5S 3G9
EMAIL: michael.sefton@utoronto.ca 

Research Areas

1. Cell Transplantation / Drug Delivery

Mammalian cells may be microencapsulated within a biocompatible polymer membrane in order to facilitate their transplantation. The polymer, being permeable to glucose and other nutrients, allows the cells to remain viable and function normally (e.g., secrete a hormone). However, the membrane is impermeable to the higher molecular weight antibodies so that the cells are not rejected when implanted. Preserving the cells' viability during encapsulation (e.g., during exposure to organic solvents) is extremely difficult and we appear to be the only group in the world that can do this with a biocompatible polymer. Our polymer (poly HEMA-MMA) is very similar to soft contact lens material. We are involved in making better polymers, designing more efficient processes for making capsules or understanding what happens to the cells, in vitro or in vivo, when they are enclosed inside the capsule. Current applications include the encapsulation of pancreatic islets for the treatment of diabetes, dopamine producing cells for the treatment of Parkinson's disease or the use of genetically modified cells for gene therapy. We are particularly interested in modulating the immune and inflammatory response using genetically modified cells to these capsules upon implantation.

2. Biomaterials

We are also investigating blood compatible materials. Blood clots when it comes into contact with synthetic materials. Hence in the preparation of devices that are used in contact with blood (e.g., artificial heart, vascular grafts, catheters), techniques must be used to disperse clots or prevent their formation. The administration of anticoagulants (heparin) is commonly used to prevent the blood from clotting (however their use may lead to excessive bleeding). In the past our approach was to covalently immobilize heparin onto the material surface, through a polyvinyl alcohol (PVA) coating layer. This has been very effective in preventing adherent clots but embolization and the consumption of platelets continues to be a problem. Hence we have focused on understanding why PVA is reactive and on developing alternatives to PVA that can be heparinized yet are not so reactive. Flow cytometry and other immunologically based techniques are fundamental to these studies. We are also interested in the links among coagulation, platelet and leukocyte activation and complement activation. This and our interest in cell encapsulation has lead us to investigate the mechanism of biomaterial associated inflammation.

3. Tissue Engineering

These projects relate to the University of Toronto initiative in Tissue Engineering which is described more fully elsewhere. Although these problems have a significant biomedical orientation (making them suitable as thesis projects for non-engineering students), the difficulties that arise generally necessitate the use of well established engineering approaches. Hence a student in this area will have the background to handle difficult problems not only in biomedical engineering but in other areas also.

 

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SELECTED PUBLICATIONS (since 2000):

J.E. Babensee, M.V. Sefton, “Viability of HEMA-MMA Microencapsulated Model Hepatoma Cells in Rats and the Host Response”, Tiss. Eng., 6, 165-182 (2000).

S. Lahooti, M.V. Sefton, “Microencapsulation of Normal and Transfected L929 Fibroblasts in a HEMA-MMA Copolymer”, Tiss. Eng., 6, 139-149 (2000).

S. Lahooti and M. V. Sefton, “Agarose Enhances the Viability of Intraperitoneally Implated microencapsulated L929 fibroblasts”, Cell Transpl. 9, pp. 785-796 (2000).

Sefton, M.V., Gemmell, C.H., Gorbet, M.B., "What Really is Blood Compatibility?", J. Biomat., Sci. Polymer Edn., 11, pp. 1165-1182 (2001).

M.V. Sefton , "Perspective on Hemocompatibility Testing", J. Biomed. Mater. Res. 55, pp. 445-446 (2001).

M.V.Sefton, A. Sawyer, M.Gorbet, J.P.Black, E. Cheng, C.Gemmell, E. Cooper-Pottinger, "Does Surface Chemistry Affect Thrombogenicity of Surface Modified Polymers?" J. Biomed . Mater. Res. 55, 447-459 (2001).

M.B.Gorbet, M.V.Sefton, “Expression of Procoagulant Activities on Leukocytes Following Contact with Polystyrene and PEG Grafted Polystyrene Beads”, J. Lab. Clin. Med., 137, pp. 345-355 (2001).

M.B. Gorbet and M.V. Sefton, "Material-induced Tissue Factor expression but not CD11b upregulation depends on the presence of platelets", J.Biomed.Mater.Res., 67, pp. 792-800 (2003).

M.B. Gorbet and M.V. Sefton, "Biomaterial associated thrombosis: roles of coagulation factors, complement, platelets and leukocytes, Biomaterials, 25, pp.5681-5703 (2004). [republished as one of best 25 papers published in Biomaterials from 1980-2004, in The Biomaterials Silver Jubilee Compendium, ed D.F. Williams, Elsevier, 2005]

P. Xu and M.V. Sefton, "Expression of Matrix Metalloproteinase -2 and -9 in Exudates Associated with Polydimethyl Siloxane and Gelatin tubes Implanted in Mice", J. Biomed. Mater. Res., 71A, pp.226-232 (2004).

K. Jones, M.V. Sefton and R. Gorczynski, “In Vivo Recognition by the Host Adaptive Immune System of Microencapsulated Xenogeneic Cells”, Transplantation, 78(10), pp.1454-1462 (2004)

M.B. Gorbet, and M.V. Sefton, “Complement inhibition reduces material-induced leukocyte activation with PEG modified polystyrene beads (Tentagel™) but not polystyrene beads”, J. Biomed. Mater. Res.: Part A 74A, 511-522 (2005).

M.B. Gorbet and M.V. Sefton. Endotoxin: the uninvited guest. Biomaterials. 26(34):6811-7 (2005)

A.Khademhosseini, M.H. May, and M.V. Sefton, “Conformal Coating of Mammalian Cells Immobilized onto Magnetically Driven Beads”, Tissue Engineering, 11, 1797-1806. (2005)

A. Sosnik and M.V. Sefton, Semi-synthetic collagen/poloxamine matrices for Tissue Engineering, Biomaterials, 26, 7425-7435 (2005)

A.Sosnik, and M.V. Sefton, “Poloxamine hydrogels with a quaternary ammonium modification to improve cell attachment”, Journal of Biomed. Mater. Res. 75A, 295-307 (2005).

A. Sosnik A. and M.V. Sefton, Methylation of poloxamine for enhanced cell adhesion, Biomacromolecules, 7, 331-338 (2006).

A. P. McGuigan and M. V. Sefton “Vascularized Organoid Engineered by Modular Assembly Enables Blood Perfusion”, PNAS 103, 11461–11466 (2006).

K. S. Jones, M. V. Sefton and R.M. Gorczynski , Suppressed splenocyte proliferation following a xenogeneic skin graft due to implanted biomaterials., Transplantation. 82, 415-421 (2006).

M. She, A. P. McGuigan and M. V. Sefton, Tissue factor and thrombomodulin expression on endothelial cell seeded collagen modules for tissue engineering, J. Biomed Mater. Res 80, 497-504 (2007)

A. P. McGuigan and M. V. Sefton, Design and fabrication of sub-mm sized modules containing encapsulated cells for modular tissue engineering, Tissue Engineering 13(5): 1069-1078 (2007)

A. P. McGuigan and M. V. Sefton, Design criteria for a modular tissue-engineered construct, Tissue Engineering 13(5): 1079-1089 (2007)

M. J. Butler and M.V. Sefton A poly(butyl methacrylate-co-methacrylic acid) tissue engineering scaffold with proangiogenic potential in vivo, J. Biomed. Mater. Res. 82A: 265-273 (2007)

A. P. McGuigan and M. V. Sefton, The influence of biomaterials on endothelial cell thrombogenicity, Biomaterials 28:2547-2571(2007)

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• Tissue Engineering