Rebuilding the brain
The study of the brain is among the most exciting frontiers in modern medical science. As neural tissue engineer Associate Professor John Forsythe is discovering, the brain has potential not previously imagined, perhaps even the potential to regenerate.
John initially joined Monash as part of the CRC Polymers team, researching commodity polymers, such as everyday plastic packaging.
However, he has made a dramatic shift in his research focus, and begun work in what has become his passion: neural tissue engineering.
Within this rapidly developing field John is applying his knowledge of materials engineering, biomaterials and nanotechnology to help develop new therapies to regenerate damaged neural pathways in the brain. The work offers hope for potential new treatments of neurodegenerative diseases such as Parkinson’s and Huntington’s diseases.
“I made the shift because I saw an interest in this new, interdisciplinary field, and I felt my research could make a difference and help people,” John says.
“That means a lot, at the end of the day.”
John works with leading neurologists and stem cell scientists, creating biomaterial structures to encase stem cells implanted in the brain, helping them survive, differentiate and grow in specific ways to potentially repair nerves and restore function.
This is a complicated business. The brain has evolved over millennia to resist great change in adulthood – it’s an innate survival mechanism to prevent critical, hard-wired processes from being erased. So John and his colleagues must trick the brain into accepting the foreign cells, and at the same time create an environment to encourage the growth of stem cells.
Working at the nanoscale, John creates temporary biological or synthetic structures (sometimes a mix of both) to protect and direct the implanted cells. He is also studying the use of different materials at the surfaces of these structures to aid cell growth and survival, delving further into a new branch of science, bionanotechnology.
“We are utilising concepts that are established in nanotechnology and applying them in the biological setting,” John says.
“We need to get down to the nanoscale because the cells interact differently at that level. In fact if you look at the brain, it is itself nanostructured. So we are trying to replicate this nanostructure of the brain in the artificial matrix that we are making, taking cues or signals from what the brain looks like, and building that artificially in these scaffolds.
“This interface between nanotechnology, materials engineering and neurology is really exciting, and they can feed off each other really well.”
Collaboration and cross-disciplinary research is integral to John’s work. His nanostructures are being used in a number of projects with partners such as the Australian Regenerative Medicine Institute, the Howard Florey Institute, the Mental Health Institute Victoria, the Monash Immunology and Stem Cell Laboratories, the CSIRO and the Monash Institute of Medical Research.
John is also currently collaborating on the Monash Vision Group’s bionic eye project. He will help develop neural prosthetics, electrodes that have increased compatibility with the brain and act as an implanted receiver, passing signals from external cameras directly to the visual cortex. The project has the potential to radically improve the freedom and living standards of people with severe vision impairment.
Pettikiriarachchi, J., Parish, C., Nisbet, D.R., Forsythe, J.S., 2011, Architectural and surface modification of nanofibrous scaffolds for tissue engineering, in Polymeric Nanomaterials, eds S. S. R. Challa Kumar, Wiley-VCH, Weinheim Germany, pp. 397-427.
Menzies, D.J., Jasieniak, M., Griesser, H.J., Forsythe, J.S., Johnson, G., McFarland, G., Muir, B.W., 2012, A ToF-SIMS and XPS study of protein adsorption and cell attachment across PEG-like plasma polymer films with lateral compositional gradients, Surface Science [P], vol 606, issue 23-24, Elsevier Science BV, Amsterdam The Netherlands, pp. 1798-1807.
Menzies, D., Nelson, A., Shen, H., McLean, K., Forsythe, J., Gengenbach, T., Fong, C., Muir, B., 2012, An x-ray and neutron reflectometry study of 'PEG-like' plasma polymer films, Journal Of The Royal Society Interface [P], vol 9, issue 70, The Royal Society, London UK, pp. 1008-1019.
Wang, T.Y., Forsythe, J.S., Parish, C., Nisbet, D.R., 2012, Biofunctionalisation of polymeric scaffolds for neural tissue engineering, Journal of Biomaterials Applications [P], vol 27, issue 4, Sage Publications Ltd, London UK, pp. 369-390.
Zhou, K., Thouas, G.A., Bernard, C., Nisbet, D.R., Finkelstein, D.I., Li, D., Forsythe, J.S., 2012, Method to impart electro- and biofunctionality to neural scaffolds using graphene-polyelectrolyte multilayers, ACS Applied Materials & Interfaces [P], vol 4, issue 9, American Chemical Society, Washington DC USA, pp. 4524-4531.
Menzies, D.J., Gengenbach, T., Forsythe, J., Birbilis, N., Johnson, G., Charles, C., McFarland, G., Williams, R., Fong, C., Leech, P., McLean, K., Muir, B., 2012, One step multifunctional micropatterning of surfaces using asymmetric glow discharge plasma polymerization, Chemical Communications [P], vol 48, issue 13, Royal Society of Chemistry, Cambridge UK, pp. 1907-1909.
Ercole, F., Thissen, H., Tsang, K.M.C., Evans, R.A., Forsythe, J.S., 2012, Photodegradable hydrogels made via RAFT, Macromolecules [P], vol 45, issue 20, American Chemical Society, Washington DC USA, pp. 8387-8400.
Wang, T.Y., Forsythe, J.S., Nisbet, D.R., Parish, C., 2012, Promoting engraftment of transplanted neural stem cells/progenitors using biofunctionalised electrospun scaffolds, Biomaterials [P], vol 33, issue 36, Elsevier Science Ltd, Oxford UK, pp. 9188-9197.
Marchesan, S., Waddington, L., Easton, C.D., Winkler, D.A., Goodall, L., Forsythe, J.S., Hartley, P.G., 2012, Unzipping the role of chirality in nanoscale self-assembly of tripeptide hydrogels, Nanoscale [P], vol 4, issue 21, The Royal Society of Chemisty, Cambridge UK, pp. 6752-6760.
Zhou, K., Sun, G., Bernard, C.C., Thouas, G.A., Nisbet, D.R., Forsythe, J.S., 2011, Optimizing interfacial features to regulate neural progenitor cells using polyelectrolyte multilayers and brain derived neurotrophic factor, Biointerphases [P], vol 6, issue 4, SpringerOpen, Germany, pp. 189-199.
Khan, M., Fon, D., Li, X., Tian, J., Forsythe, J.S., Garnier, G., Shen, W., 2010, Biosurface engineering through ink jet printing, Colloids and Surfaces B: Biointerfaces [P], vol 75, issue 2, Elsevier B.V., Netherlands, pp. 441-447.
Nisbet, D.R., Moses, D., Gengenbach, T.R., Forsythe, J.S., Finkelstein, D.I., Horne, M.K., 2009, Enhancing neurite outgrowth from primary neurones and neural stem cells using thermoresponsive hydrogel scaffolds for the repair of spinal cord injury, Journal of Biomedical Materials Research Part A, vol 89, issue 1, Wiley-LISS, Hoboken, NJ, USA, pp. 24-35.
Crompton, K.E., Forsythe, J.S., Horne, M., Finkelstein, D.I., Knott, R., 2009, Molecular level and microstructural characterisation of thermally sensitive chitosan hydrogels, Soft Matter [P], vol 5, issue 23, Royal Society of Chemistry, Cambridge, England, UK, pp. 4704-4711.
Nisbet, D.R., Rodda, A.E., Horne, M.K., Forsythe, J.S., Finkelstein, D.I., 2009, Neurite infiltration and cellular response to electrospun polycaprolactone scaffolds implanted into the brain, Biomaterials [P], vol 30, issue 27, Elsevier, England, UK, pp. 4573-4580.
Nisbet, D.R., Forsythe, J.S., Shen, W., Finkelstein, D.I., Horne, M.K., 2009, Review paper: A review of the cellular response on electrospun nanofibers for tissue engineering, Journal of Biomaterials Applications [P], vol 24, issue 7, Sage Publications Ltd, UK, pp. 7-29.
Nisbet, D.R., Rodda, A.E., Finkelstein, D.I., Horne, M.K., Forsythe, J.S., Shen, W., 2009, Surface and bulk characterisation of electrospun membranes: Problems and improvements, Colloids and Surfaces B: Biointerfaces [P], vol 71, issue 1, Elsevier B.V., Netherlands, pp. 1-12.
Nisbet, D.R., Yu, L.M.Y., Zahir, T., Forsythe, J.S., Schoichet, M.S., 2008, Characterization of neural stem cells on electrospun poly(epsilon- caprolactone) submicron scaffolds: Evaluating their potential in neural tissue engineering, Journal of Biomaterials Science. Polymer Edition, vol 19, issue 5, Brill Academic Publishers, Leiden, The Netherlands, pp. 623-634.
Scott, T.F., Cook, W.D., Forsythe, J.S., 2008, Effect of the degree of cure on the viscoelastic properties of vinyl ester resins, European Polymer Journal [P], vol 44, issue 10, Elsevier, Oxford, UK, pp. 3200-3212.
Melville, A.J., Rodriguez-Lorenzo, L.M., Forsythe, J.S., 2008, Effects of calcination temperature on the drug delivery behaviour of Ibuprofen from hydroxyapatite powders, Journal of Materials Science: Materials in Medicine, vol 19, issue 3, Springer, Netherlands, pp. 1187-1195.
Nisbet, D.R., Crompton, K.E., Horne, M.K., Finkelstein, D.I., Forsythe, J.S., 2008, Neural tissue engineering of the CNS using hydrogels, Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol 87, issue 0, Wiley-Liss, Hoboken, NJ, USA, pp. 251-263.
Nisbet, D.R., Pattanawong, S., Ritchie, N.E., Shen, W., Finkelstein, D.I., Horne, M.K., Forsythe, J.S., 2007, Interaction of embryonic cortical neurons on nanofibrous scaffolds for neural tissue engineering, Journal of Neural Engineering, vol 4, issue 2, Institute of Physics Publishing, Bristol, UK, pp. 35-41.
Crompton, K.E., Goud, J.D., Bellamkonda, R.J., Gengenbach, T.R., Finkelstein, D.I., Horne, M.K., Forsythe, J.S., 2007, Polylysine-functionalised thermoresponsive chitosan hydrogel for neural tissue engineering, Biomaterials, vol 28, issue 3, Elsevier, England, pp. 441-449.
Spiers, K.M., Forsythe, J.S., Suzuki, K., Cashion, J.D., 2007, Production of magnetic microspheres by ultrasonic atomisation, Journal of Magnetism and Magnetic Materials, vol 311, issue 1, Elsevier BV, The Netherlands, pp. 97-100.
Hanley, T.L., Forsythe, J.S., Sutton, D., Moad, G., Burford, R.P., Knott, R.B., 2006, Crystallisation kinetics of novel branched poly(ethylene terephthalate): a small-angle X-ray scattering study, Polymer International, vol 55, issue 12, Elsevier Inc, London UK, pp. 1435-1443.
Crompton, K.E., Tomas, D., Finkelstein, D.I., Marr, M., Forsythe, J.S., Horne, M., 2006, Inflammatory response on injection of chitosan/GP to the brain, Journal of Materials Science-Materials in Medicine, vol 17, issue 7, Springer, Netherlands, pp. 633-639.
Nisbet, D.R., Crompton, K.E., Hamilton, S.D., Shirakawa, S., Prankerd, R.J., Finkelstein, D.I., Horne, M.K., Forsythe, J.S., 2006, Morphology and gelation of thermosensitive xyloglucan hydrogels, Biophysical Chemistry, vol 121, issue 1, Elsevier, The Netherlands, pp. 14-20.
Melville, A.J., Harrison, J.M., Gross, K.A., Forsythe, J.S., Trounson, A.O., Mollard, R.A., 2006, Mouse embryonic stem cell colonisation of carbonated apatite surfaces, Biomaterials, vol 27, issue 4, Elsevier Science Ltd, Kidlington England, pp. 615-622.
Forsythe, J.S., Cheah, K., Nisbet, D.R., Gupta, R.K., Lau, A., Donovan, A.R., O'Shea, M.S., Moad, G., 2006, Rheological properties of high melt strength poly(ethylene terephthalate) formed by reactive extrusion, Journal of Applied Polymer Science, vol 100, issue 5, John Wiley and Sons Inc, US, pp. 3646-3652.
Nisbet, D.R., Pattanawong, S., Nunan, J.M., Shen, W., Horne, M.K., Finkelstein, D.I., Forsythe, J.S., 2006, The effect of surface hydrophilicity on the behavior of embryonic cortical neurons, Journal of Colloid and Interface Science, vol 299, issue 2, Elsevier, USA, pp. 647-655.
Crompton, K.E., Prankerd, R.J., Paganin, D.M., Scott, T.F., Horne, M.K., Finkelstein, D.I., Gross, K.A., Forsythe, J.S., 2005, Morphology and gelation of thermosensitive chitosan hydrogels, Biophysical Chemistry, vol 117, issue 1, Elsevier, The Netherlands, pp. 47-53.
Harrison, J.M., Pattanawong, S., Forsythe, J.S., Gross, K.A., Nisbet, D.R., Beh, H., Scott, T.F., Trounson, A.O., Mollard, R.A., 2004, Colonization and maintenance of murine embryonic stem cells on poly(alpha-hydroxy esters), Biomaterials, vol 25, Elsevier Science Ltd, Kidlington UK, pp. 4963-4970.
Cook, W.D., Scott, T.F., Quay-Thevenon, S., Forsythe, J.S., 2004, Dynamic mechanical thermal analysis of thermally stable and thermally reactive network polymers, Journal of Applied Polymer Science, vol 93, issue 3, John Wiley & Sons Inc., Hoboken USA, pp. 1348-1359.
Harrison, J.M., Melville, A.J., Forsythe, J.S., Muddle, B.C., Trounson, A.O., Gross, K.A., Mollard, R.A., 2004, Sintered hydroxyfluorapatites - IV: The effect of fluoride substitutions upon colonisation of hydroxyapatites by mouse embryonic stem cells, Biomaterials, vol 25, issue 20, Elsevier Sci Ltd, UK, pp. 4977-4986.
Cook, W.D., Forsythe, J.S., Irawati, N., Scott, T.F., Xia, W.Z., 2003, Cure kinetics and thermomechanical properties of thermally stable photopolymerized dimethacrylates, Journal of Applied Polymer Science, vol 90, issue 14, John Wiley & Sons Inc., Hoboken USA, pp. 3753-3766.
Scott, T.F., Cook, W.D., Forsythe, J.S., Bowman, C.N., Berchtold, K.A., 2003, FTIR and ESR spectroscopic studies of the photopolymerization of vinyl ester resins, Macromolecules, vol 36, issue 16, American Chemical Society, Washington USA, pp. 6066-6074.
Scott, T.F., Cook, W.D., Forsythe, J.S., 2003, Photo-DSC cure kinetics of vinyl ester resins II: Influence of diluent concentration, Polymer, vol 44, issue 3, Elsevier Science Ltd., Oxford UK, pp. 671-680.
Scott, T.F., Cook, W.D., Forsythe, J.S., 2002, Kinetics and Network Structure of Thermally Cured Vinyl Ester Resins, European Polymer Journal, vol 38, issue 4, Pergamon-Elsevier Science Ltd., Oxford UK, pp. 705-716.
Becker, L.O., Simon, G.P., Rieckmann, T., Forsythe, J.S., Rosu, R., Volker, S., 2002, Phase Separation, Physical Properties and Melt Rheology of a Range of Variously Transesterified Amorphous Poly(Ethylene Terephthalate)-Poly(Ethylene Naphthalate) Blends, Journal of Applied Polymer Science, vol 83, issue 7, John Wiley & Sons Inc., Hoboken NY USA, pp. 1556-1567.
Scott, T.F., Cook, W.D., Forsythe, J.S., 2002, Photo-DSC Cure kinetics of Vinyl Ester Resins. I. Influence of Temperature, Polymer, vol 43, issue 22, Elsevier Science Ltd., Oxford UK, pp. 5839-5845.
Cook, W.D., Dean, K., Forsythe, J.S., 2001, Cure, Rheology and Properties of IPN Thermosets for Composite Applications, Materials Forum, vol 25, Institute of Materials Engineering Australasia, Melbourne Vic Australia, pp. 30-59.
Becker, L.O., Simon, G.P., Rieckmann, T., Forsythe, J.S., Rosu, R., Volker, S., O'Shea, M., 2001, Dielectric Relaxation Spectroscopy of Reactively Blended Amorphous Poly(ethylene terephthalate)-poly(ethylene naphthalate) Films, Polymer, vol 42, issue 5, Elsevier Sci. Ltd., Oxford UK, pp. 1921-1929.
Forsythe, J.S., Hill, D.J., Mohajerani, S., Whittaker, A., 2001, Solid State 19F NMR Determination of New Structure Formation in FEP Following Radiolysis at 300 and 363 K, Radiation Physics and Chemistry, vol 60, Permagon-Elsevier Science Ltd., Oxford UK, pp. 439-444.
Goodwin, A.A., Whittaker, A.K., Jack, K.S., Hay, J.N., Forsythe, J.S., 2000, Absorption of low molecular weight penetrants by a thermoplastic polyimide, Polymer, vol 41, Elsevier Science, Oxford UK, pp. 7263-7271.
Forsythe, J.S., Hill, D.J.T., 2000, The radiation chemistry of fluoropolymers, Progress in Polymer Science, vol 25, Pergamon-Elsevier Science, Oxford UK, pp. 101-136.
Khan, M., Fon, D., Li, X., Forsythe, J.S., Thouas, G.A., Garnier, G., Shen, W., 2008, Printing biomolecules part-1: Achieving total control of biomolecule delivery using ink jet printing, Chemeca 2008, 28 September 2008 to 1 October 2008, Engineers Australia, Newcastle, NSW, Australia, pp. 744-753.
Wang, X., Gan, K.S., Phadtajaphan, S., Forsythe, J.S., Rhodes, M.J., 2002, The influence of interparticle forces on gas fluidization, Proceedings of 6th World Congress of Chemical Engineering, 23/09/2001 to 27/09/2001, Institute of Chemical Engineers in Aust, Melbourne Vic Australia, p. cd.
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