Gene activated matrices for bone and cartilage regeneration in arthritis

Christian Plank, David Eglin, Niamh Fahy, Cedric Sapet, Pascal Borget, Gerjo Van Osch, Chiara Gentili, Thomas Miramond, Katharina Zöller, Martina Anton*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

The GAMBA Consortium is developing a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The scientific and technological 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 will 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 or colonising 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 growth factor transgenes. This concept is implemented by a multidisciplinary team from leading European institutions. Here, we report on the concepts, objectives and some preliminary results of the GAMBA project which is funded in 7th Framework Programme of the European Union THEME [NMP-2009-2.3-1], Biomimetic gels and polymers for tissue repair.

Original languageEnglish
Pages (from-to)17-32
Number of pages16
JournalEuropean Journal of Nanomedicine
Volume4
Issue number1
DOIs
Publication statusPublished - 27 Mar 2012

Bibliographical note

Funding Information:
The authors gratefully acknowledge major contributions by the following principle investigators and/or researchers of the GAMBA consortium: Christian Koch and Youlia Kostova (TU M ü nchen), Mauro Alini and Matteo D ’ Este (AO Research Institute), Mary Murphy, Eric Farrell and Thomas Ritter (REMEDI), Olivier Zelphati (OZ Biosciences), Rui Pereira and Ranieri Cancedda (Istituto Nazionale per la Ricerca sul Cancro), Guy Daculsi (INSERM), Sven Siebert (ScienceDialogue). This research was supported by the FP7 EU-Project “GAMBA” NMP3-SL-2010-245993.

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