Identification and Optimisation of Atomic Scale Influences on Cell Response to Novel Bioactive Glass and Nanocomposite Tissue Scaffolds

Lead Research Organisation: Imperial College London
Department Name: Materials

Abstract

The aim of the proposed project is to develop new scaffold materials as osteogenic templates for bone regeneration that could play a key role in revolutionising healthcare in this area. The project is at the interface of Materials Science, Physics and Biology. Novel nanocomposites (calcium silicate/ polymer) will be developed that mimic the structure of bone both at the nanoscale, where bone is a nanoscale composite of collagen (polymer) and bone mineral (ceramic), and at the macroscale, where cancellous bone has a network of macropores. Through this project, the influence of changes in nano and atomic scale structure on bone cell response of these new materials and bioactive glass (calcium silicate) scaffolds will be investigated for the first time. The scaffolds will be optimised from atomic to the macro scale for bone growth. The scaffolds will be based on bioactive sol-gel derived glasses that bond to bone and dissolve in the body, releasing ionic products that stimulate new bone growth. The nanocomposites are expected to do the same although little is known about how the nanostructure of the either material affects cell response. This proposal seeks to rectify this by:1) Using cutting-edge characterisation techniques, such as NMR. synchrotron source X-ray diffraction (XRD) and neutron diffraction (ND), to investigate how processing variables (e.g. final processing temperature and polymer content) affect the scaffold nanostructure and mechanical properties. Not only will well developed aspects of these techniques be employed, but new avenues will be explored to include 17O and 43Ca MAS NMR (the latter of which is little studied), in situ XRD to examine the structural developments of the amorphous structure in real time and precise isotope ND difference experiments2) Investigating the effect of nanoscale structural changes on degradation and bioactivity, and3) quantifying how changing the nanostructure of the scaffolds affects in vitro bone growth. Mechanisms of bioactivity with respect to the amorphous calcium-silicate structure will be clarified.

Publications

10 25 50

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Ji L (2011) Template synthesis of ordered macroporous hydroxyapatite bioceramics. in Chemical communications (Cambridge, England)

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Jones J (2009) New trends in bioactive scaffolds: The importance of nanostructure in Journal of the European Ceramic Society

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Jones JR (2010) Bioactive glass scaffolds for bone regeneration and their hierarchical characterisation. in Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine

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Jones JR (2009) Quantifying the 3D macrostructure of tissue scaffolds. in Journal of materials science. Materials in medicine

 
Description A range of cutting edge characterisation methods were used to understand sol-gel glass structure and how it affects cellular response.

The sol-gel process is used to produced porous scaffolds for tissue engineering applications. The nano porosity of sol-gel glasses evolves by the assembly of nano particles. Calcium needs to be incorporated into the silicate network and released at a controlled rate for bioactivity, but here we found that a temperature of 450C is needed to get the calcium into the silicate network.

sol-gel glass scaffolds stimulated human stem cells to differentiate into bone cells.

Introduction of natural polymers such as gelatin can be introduced into the sol-gel foaming process to create flexible hybrid biomaterials. if the correct coupling agent is used, silica and gelatin can interact at the molecular level to produce a flexible material and the rate of silica and gelatin dissolution can be made to be congruent (a true hybrid).
Exploitation Route Up-scaling and commercialisation routes explored with RepRegen Intellectual property - patent filed with Imperial Innovations, licensed to RepRegen Ltd, a medical device company
Sectors Healthcare

 
Description Patent Jones, J. R., Poologasundarampillai, G., Hill R. G. "Bioactive nanocomposite material" WO2009030919 A3 was licensed by Repregen Ltd. Materials developed feature in the Victoria and Albert Museum, the Institute of Making's Materials Library and featured in Daily Mail, Daily Express and Mirror articles.
First Year Of Impact 2010
Sector Education,Healthcare
Impact Types Economic

 
Description EPSRC Challenging Engineering
Amount £1,175,383 (GBP)
Funding ID EP/I020861/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 06/2011 
End 05/2016
 
Description EPSRC PHD PLUS for Oliver Mahony
Amount £94,600 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 11/2010 
End 10/2011
 
Description FP7 Marie Curie Fellowship for Yuliya Vueva
Amount € 200,000 (EUR)
Funding ID HABR 
Organisation European Commission 
Department Seventh Framework Programme (FP7)
Sector Public
Country European Union (EU)
Start 09/2012 
End 09/2014
 
Description TSB Feasibility Grant
Amount £100,000 (GBP)
Organisation Innovate UK 
Sector Public
Country United Kingdom
Start 03/2010 
End 09/2010
 
Description Nanocomposites for bone regeneration 
Organisation Nagoya Institute of Technology
Country Japan 
Sector Academic/University 
PI Contribution Julian Jones was appointed Visiting Professor, giving an annual seminar at Nagoya Institute of Technology. Post doctoral researcher Gowsihan Poologasaundarampillai employed at Nagoya Institute of Technology for 18 months, PhD student Sen Lin appointed as a post doctoral researcher at Nagoya Institute of Technology for 12 months. Hosted Dr Akiko Obata (Assistant Professor) for 1 year , Jin Nakamura (PhD student) for 1 year and Sungho Lee (PhD Student) for 3 months. Maria Nelson and Lizzie Norris (PhD students) visited Nagoya for 3 Months each. Anthony Macon employed from Jones' group as an Assistant Professor. Hosted 4 Masters students from NiTech. Associate Professors Akiko Obata and Toshihisa Mizuno joined Jones' group for 2 months and 1 year respectively.
Collaborator Contribution Exchange Programme funded through JSPS Sent 9 researchers to Julian Jones' research group Employed a post doctoral researcher and a phd student from Julian Jones' research group Employed and Assistant Professor from Julian Jones' group
Impact Maçon, A. L. B., Lee, S., Poologasundarampillai, G., Kasuga, T., Jones, J. R. "Synthesis and dissolution behaviour of CaO/SrO-containing sol-gel-derived 58S glasses" Journal of Materials Science, 2017, DOI: 10.1007/s10853-017-0869-0.Wang, J., Zhou, P., Obata, A., Jones, J. R., Kasuga, T. "Preparation of cotton-wool-like poly(lactic acid)-based composites consisting of core-shell-type fibers", Materials. 2015: 8: 7979-7987, DOI :10.3390/ma8115434 Gao, C. X., Ito, S., Obata, A., Mizuno, T., Jones, J. R., Kasuga, T. "Fabrication and in vitro characterization of electrospun poly (gamma-glutamic acid)-silica hybrid scaffolds for bone regeneration" Polymer, 2016: 91:106-117. DOI: 10.1016/j.polymer.2016.03.056. Wang, J., Zhou, P., Obata, A., Jones, J. R., Kasuga, T. "Preparation of cotton-wool-like poly(lactic acid)-based composites consisting of core-shell-type fibers", Materials. 2015: 8: 7979-7987, DOI :10.3390/ma8115434. Poologasundarampillai, G., Wang, D., Li, S., Nakamura, J., Bradley, R., Lee, P. D., Stevens, M. M., McPhail, D. S., Kasuga, T., Jones, J. R., "Cotton-wool-like bioactive glasses for bone regeneration", Acta Biomaterialia, 2014: 10: 3733-3746. Obata, A., Ito, S., Iwanag, N., Mizuno, T., Jones, J. R., Kasuga, T. "Poly(?-glutamic acid)-silica hybrids with fibrous structure: effect of cation and silica concentration on molecular structure, degradation rate and tensile properties" RSC Advances, 2014: DOI: 10.1039/c4ra08777a. Wang, D., Poologasundarampillai, G., van den Bergh, W., Chater, R., Kasuga, T., Jones, J. R., McPhail, D. S. "Strategies for the chemical analysis of highly porous bone scaffolds using secondary ion mass spectrometry (SIMS)" Biomedical Materials, 2014: 9 (1): 015013. Nakamura, J., Poologasundarampillai, G., Jones, J. R., Kasuga, T. "Tracking the formation of vaterite particles containing aminopropyl-functionalized silsesquioxane and their structure for bone regenerative medicine" Journal of Materials Chemistry B, 2013: 1: 35: 4446-4454. Obata, A. Ozasa, H., Kasuga, T., Jones, J. R. "Cotton wool-like poly(lactic acid)/vaterite composite scaffolds releasing soluble silica for bone tissue engineering" Journal of Materials Science: Materials in Medicine, 2013: 24: 1649-1658. Fujikura, K., Obata, A., Lin, S., Jones, J. R., Law, R. V., Kasuga, T. "Preparation of electrospun poly(lactic acid)-based hybrids containing siloxane-doped vaterite particles for bone regeneration" Journal of Biomaterials Science, Polymer Edition 2012: 23:10, 1369-1380 Obata, A. Hasegawa, D., Nakamura, J., Jones, J. R., Kasuga, T. "Induction of hydroxycarbonate apatite formation on polyethylene or alumina substrates by spherical vaterite particles deposition", Materials Science and Engineering C, 2012: 32: 1976 - 1981. Obata, A., Jones, J. R., Akiyoshi, S., Kasuga, T. "Sintering and crystallization of phosphate glasses by CO2-Laser irradiation on hydroxyapatite ceramics" International Journal of Applied Ceramic Technology, 2012: 9: 541-549. Obata, A., Hashimoto, T., Kasuga, T., Jones, J. R. "Hydroxyapatite coatings incorporating silicon ion releasing system on titanium prepared by using water glass and vaterite" Journal of American Ceramics Society, 2011: 94 (7): 2074-2079. Wakita, T. Obata, A., Poologasundarampillai, G., Jones, J. R., Kasuga, T., "Preparation of siloxane-containing poly(lactic acid)-vaterite hybrid membranes for guided bone regeneration" Composites Science and Technology, 2010: 70: 1889-1893.
Start Year 2009
 
Description Reactions of organosilanes in the sol-gel process 
Organisation University of Milano-Bicocca
Country Italy 
Sector Academic/University 
PI Contribution PhD students Louise Connell, Oliver Mahony and Francesca Tallia visited Bicocca to understand the reactivity of the organosilane GPTMS Hosted PhD student Laura Russo
Collaborator Contribution Laura Russo developed a new hybrid based on Silica and PEG Hosted Louise Connell and Oliver Mahony and investigated the reaction of GPTMS with water and nucleophiles Tall developed a new hybrid with self-healing properties
Impact EPSRC Healthcare Impact Partnership Grant "Additive manufacturing of advanced medical devices for cartilage regeneration: minimally invasive early intervention" Connell, L. S., Gabrielli, L., Mahony, O., Russo, L., Cipolla, L., Jones, J. R. "Functionalizing natural polymers with alkoxysilane coupling agents: reacting 3-glycidoxypropyl trimethoxysilane with poly(?-glutamic acid) and gelatin" Polymer Chemistry, 2017: 8: 1095-1103, DOI: 10.1039/c6py01425a. Gabrielli, L., Connell, L. S., Russo, L., Jiménez-Barbero, J., Nicotra, F., Cipolla, L., Jones, J. R. Exploring GPTMS reactivity against simple nucleophiles: chemistry beyond hybrid materials fabrication, RSC Advances, 2014: 4: 1841 - 1848. Russo, L., Gabrielli, L., Valliant, E. M., Nicotra, F., Jiménez-Barbero, J., Cipolla, L., Jones, J. R. "Novel silica/bis(3-aminopropyl) polyethylene glycol inorganic/organic hybrids by sol-gel chemistry" Materials Chemistry and Physics, 2013:140: 168-175. Gabrielli, L., Russo, L. Poveda, A., Jones, J. R., Nicotra, F., Jiménez-Barbero, J., Cipolla, L. "Epoxide opening versus silica condensation during sol-gel hybrid biomaterial synthesis", Chemistry, a European Journal, 2013: 19: 7856-7864.
Start Year 2010
 
Title Bioactive nanocomposite material 
Description A hybrid of poly-gamma-glutamic acid polymer and sol-gel silica, bonded through an organosilane coupling agent. 
IP Reference WO2009030919 
Protection Patent application published
Year Protection Granted
Licensed Yes
Impact A TSB grant was obtained by Repregen to accelerate translation.