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Project Description

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Gene Activated Matrices for Bone and Cartilage Regeneration in Arthritis

This consortium develops a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The S&T objectives of this project are complemented with an innovative program of public outreach, actively linking patients and society to the evolvement of this project. The GAMBA platform is going to implement a concept of spatiotemporal control of regenerative bioactivity on command and demand. A gene-activated matrix is a biomaterial with embedded gene vectors that will genetically modify cells embedded in the matrix. The platform comprises modules that self-adapt to the biological environment and that can be independently addressed with endogenous biological and exogenous physical or pharmacological stimuli, resulting in a temporally and spatially coordinated growth factor gene expression pattern. This reproduces, within the matrix, key elements of natural tissue formation. The modules are a biomimetic hyaluronan gel, a ceramic matrix, growth factor-encoding gene vector nanoparticles, magnetic nanoparticles and mesenchymal stem cells. Anatomical adaptivity is achieved with engineered thermal properties of the polymer matrix, which embeds other modules, selected according to functional requirements. Mechanical support is provided by Micro Macroporous Biphasic Calcium Phosphate (MBCP™), a resorbable material approved for clinical use. Spatiotemporal control of bioactivity and responsiveness to physiological conditions is represented, firstly, in the spatial distribution and release profiles of gene vectors within the composite matrix and, secondly, by letting local and external biological or physical stimuli activate the promoters driving the expression of vector-encoded transgenes. This innovative concept is implemented by a multidisciplinary team from leading European institutions combining scientific excellence with a focused plan of dissemination, public participation, gender equality and transition to market.

See current news about the project in the public GAMBA Project Discussion Room.

Publications

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ScienceDialogue   Basic Research into Regeneration of Bone and Cartilage in Osteoarthritis
A Manual for patient and citizen panels regarding ethical, legal and social aspects of innovative therapies with adult stem cells, gene therapy and nanoparticles
  English    Download 
pdf, 2.6 Mb
ScienceDialogue   Basic Research into Regeneration of Bone and Cartilage in Osteoarthritis
Compendium to the Manual. Basics, Need-to-know, History
  English    Download 
pdf, 3,4 Mb
ScienceDialogue   Grundlagenforschung zur Regeneration von Knorpel und Knochen bei Arthrose
Ein Handbuch für Bürger- und Patientenforen zu ethischen, rechtlichen und sozialen Aspekten innovativer Therapien mittels adulter Stammzellen, Gentherapie und Nanopartikel
  German    Download 
pdf, 813 Kb
ScienceDialogue   Grundlagenforschung zur Regeneration von Knorpel und Knochen bei Arthrose
Begleitbuch zum Handbuch: Grundlagen, Wissenswertes, Historie
  German    Download 
pdf, 1 Mb
     
Daculsi, G., and Miramond, T. (2012). Calcium phosphate derived biomaterials. In Encylopedia of Biophysics, G. Roberts, ed., pp. 206-211.   Link
Daculsi, G., Miramond, T., Borget, P., and Baroth, S. (2012). Calcium Phosphate Bioceramic scaffold for bone tissue engineering. Key Engineering Materials 529-530, 19-23.   Link
de Vries-van Melle, M.L., Mandl, E.W., Kops, N., Koevoet, W.J., Verhaar, J.A., and van Osch, G.J. (2012). An osteochondral culture model to study mechanisms involved in articular cartilage repair. Tissue Eng Part C Methods 18, 45-53.   Link

D'Este, M., Alini, M., and Eglin, D. (2012). Single step synthesis and characterization of thermoresponsive hyaluronan hydrogels. Carbohydr Polym 90, 1378-1385.

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D'Este, M., Alini, M., and Eglin, D. (2012). A new single step synthesis for thermoresponsive hyaluronan hydrogels. Eur Cell Mater 23, Suppl. 2, 3.

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D'Este, M., and Eglin, D. (2013). Hydrogels in calcium phosphate moldable and injectable bone substitutes: Sticky excipients or advanced 3-D carriers? Acta Biomater 9, 5421-5430.

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Fahy, N., Farrell, E., Ryan, A., Harte, M., Ritter, T., and Murphy, M. (2012). Attenuation of Inflammation by Immune Modulation for Cartilage Repair in Osteoarthritis. J Tissue Eng Regen Med 6, Suppl. 1, 63.

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Leszczynsk, A., Farrell, E., O'Doherty, A., Barry, F., O'Brien, T., and Murphy, M. (2012). Vessel derived stem cells contribute to endochondral ossification of atherosclerotic plaque (Effect of Inflammatory cytokines). J Tissue Eng Regen Med 6, Suppl. 1, 32.

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Miramond, T., Aguado, E., Goyenvalle, E., Borget, P., Baroth, S., and G., D. (2012). In vivo Comparative study of two injectable/moldable Calcium phosphate Bioceramics. Key Engineering Materials 529-530, 291-295.

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Miramond, T., Borget, P., Colombeix, C., Baroth, S., and Daculsi, G. (2012). Composite bioceramics/polymer electrospun scaffolds for regenerative medicine. Key Engineering Materials 529-530, 441-446.

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Pereira, R.C., Scaranari, M., Benelli, R., Strada, P., Reis, R.L., Cancedda, R., and Gentili, C. (2013). Dual effect of platelet lysate on human articular cartilage: a maintenance of chondrogenic potential and a transient pro-inflammatory activity followed by an inflammation resolution. Tissue Eng Part A, 19 (11-12), 1476-1488.

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Plank, C., Eglin, D., Fahy, N., Sapet, C., Borget, P., Van Osch, G., Gentili, C., Miramond, T., Zöller, K., and Anton, M. (2012). Gene activated matrices for bone and cartilage regeneration in arthritis. Eur J Nanomed 4, 17-32.

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Plank, C., Alini, M., Murphy, M., Zelphati, O., Borget, P., van Osch, G., Gentili, C., Daculsi, G., Zöller, K., and Anton, M. (2012). Gene activated matrices for bone and cartilage regeneration in arthritis -GAMBA - an EU funded project. J Tissue Eng Regen Med 6, Suppl. 1, 415.

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Sapet, C., Pellegrino, C., Laurent, N., Sicard, F., and Zelphati, O. (2012). Magnetic nanoparticles enhance adenovirus transduction in vitro and in vivo. Pharm Res 29, 1203-1218.

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M.T. Berninger, T.D. Henning, G. Wexel, E.J. Rummeny, A.B. Imhoff, M. Anton, S. Vogt (2013). Treatment of Osteochondral Defects in the Rabbit's Knee Joint by Implantation of Allogeneic Mesenchymal Stem Cells in Fibrin Clots. Journal of Visualized Experiments, 75, e4423, 21.05.2013.

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C. Sapet, C. Formosa, F. Sicard, E. Bertosio, O. Zelphati and N. Laurent (2013). 3D-fection: cell transfection within 3D scaffolds and hydrogels. Therapeutic Delivery, 4 (6), 673-685, June 2013.

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Zöller, K., Laien diskutieren und bewerten Wissenschaft: Partizipation bei Wissenschaftsthemen. Erfahrungen und Qualitätsanforderungen. 2013 Umwelt und Mensch Informatinsdienst (UMID) 2-2013; 67-74.   Link
deVries-van Melle M.L., Narcisi, R., Kops, N., Koevoet, J.L.M., Bos, P.K., Murphy, J.M., Verhaar, J.A.N., van der Kraan, P.M., van Osch, G.J.V.M.. 2013. Chondrogenesis of mesenchymal stem cells in an osteochondral environment is mediated by the subchondral bone. Tissue Engineering Part A [epub ahead of print 27.08.2013]   Link
Barry F, Murphy M. (2013). Mesenchymal stem cells in joint disease. Nat Rev Rheumatol [epub ahead of print Jul 23, 2013]   Link
Miramond T. et al. (2013). Osteopromotion of Biphasic Calcium Phosphate granules in critical size defects after osteonecrosis induced by focal heating insults. IRMB 34(4-5): 337-341.   Link
PC Kreuz, C Gentili, B Samans, D Martinelli, JP Krüger, W Mittelmeier, M Endres, R Cancedda, C Kaps. 2013 Scaffold-assisted cartilage tissue engineering using infant chondrocytes from human hip cartilageOsteoarthritis Cartilage. 2013  [epub ahead of print 07.09.2013]   Link
Zöller, K: Science and the Lay Perspective: Lay Peoples’ involvement in assessing Tissue Engineering Issues. 2013. Tissue Engineering Part C (epub ahead of print 01.10.2013)   Link

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