Community Research and Development Information Service - CORDIS

Periodic Report Summary 1 - FIBROGELNET (Network for Development of Soft Nanofibrous Construct for Cellular Therapy of Degenerative Skeletal Disorders)

The major objective of FIBROGELNET project ( is to bring together the expertise of academia and industry partners for the development of an innovative complementary strategy for targeting bone and cartilage regeneration. Considering the achievements and draw-backs of contemporary techniques in tissue engineering and related disciplines, the project concept is based on a novel combination of already established techniques to generate an advanced tissue engineering construct comprising of bioinspired gel with unique biomechanical properties containing oriented nanofibres and bioactive molecules resembling the natural spatiotemporal cues of the extracellular matrix. It is further combined with human mesenchymal stem cells (hMSC) constraint to differentiate into osteogenic or chondrogenic lineages. FIBROGELNET is designed to supplement the existing EuroNanoMed project (STRUCTGEL) with simillar innovative strategy for targeting bone and cartilage regeneration.
The work performed in IBEC (the coordinating unit) and UPVLC for the reporting period was dedicated primarily on the development of “material’s part” of the project. UPVLC assured production of gel-slices according to WP1 tasks, while IBEC was involved in the preparation of nanofibers and their deposition on these slides, according WP2 (Task 1 and Task 2).
Most visited unit for the reporting period was BioElpida (3 ESR<4, 1 ER<10 and 2 ER>10), connected with the executing of WP5: “Upscaling of production and adaptation to GMP requirements”. Bioelpida is a biotechnology manufacturing company located in Lyon, France with specific expertise in the manufacture of cell based products. The company is authorized by the French agency for the safety of health products (AFSSAPS) for the manufacture and testing of pharmaceutical products. The planned tasks at this stage included particularly the theoretical and practical training on GMP conditions. The students received a theoretical training in manufacturing, production, quality control (QC) and quality assurance (QA) that were conducted by the respective Units at Bioelpida and administered by Benoit Pinteur (the CEO of the company) and Eric Garcia. The Production unit gave insight into recent preparation of GMP-conform products. The example product was an autologous anti-cancer vaccine produced partly in BioElpida. The two ER>10 performing 2Mo secondments were the group leaders of IBEC (Prof Altankov) and MLU (Prof Thomas Groth) who were mainly involved in the discussion on the possibility for GMP assent production of FIBROGELNET construct, but they received also a general training course on GMP production.
MLU has also hosted one ESR<4 from BioElpida who learned how to produce multilayers with different polyelectrolytes including matrix proteins and polypeptide-based multilayer systems according WP3. The principal experiment was to study the effect of multilayers on hMSC induced to chondrogenic and osteogenic differentiation. Biocompatibility studies of multilayers were also carried.
From scientific point of view, it has to be noted the studies performed in IBEC, conducted by the recruited ER>10 Dr Tatiana Coelho in the frame of her 12 Mo secondment. These studies might be divided in 2 parts: Task 1: Study on early events of MSCs chondrogenic differentiation, including: (a) expression of some ECM proteins and (b) Effect of Wnts; and Task 2: Development of methodology to assess thickness and composition of putative cartilage tissue, including: (a) slicing of pellets; (b) slicing of tissue sheets from FIBROGELNET 2D and 3D constructs. These studies were also supported by the core EuroNanoMed project (STRUCTGEL) utilising quantitative real time PCR (targeting Col 2, Col 10 and SOX 9 genes).
Surprisingly, the results obtained provided two important messages, that: (i) cartilage development is almost independent on fibers orientation (except for Col 2, where random fibers significantly override the aligned ones), and (ii) cartilage development is better in 2D conditions (single slides) vs. 3D environment (sandwich-like configuration). These results are planned to be confirmed within next year in the University of Glasgow (Prof Manuel Sanchez group) after confirmation the Amendment for their inclusion in the project.
Significant body of work was performed in MLU (Germany) according WP3 - Entrapment of bioactive molecules and assembly of the construct. Deliverable 3.1 reports about a successful preparing of such polyelectrolyte multilayers based on chitosan as polycation and heparin as polyanion. BMP-2 was selected for these initial studies because as most growth factors it share heparin binding domains. The potential for loading of FIBROGELNET toolbox with bioactive factors is demonstrated in Milestone 3.1 by the ability to generate a bioactive system that allows the long-term release of BMP-2 over periods of several days that would enable MSCs to differentiate into the desired tissue. The measurements of long-term release of BMP-2 over a time of 3 weeks shows striking differences in release behaviour dependent on the pH value used for preparation of multilayer systems and type of terminal layer.
Apart from the interesting results obtained on chondrogenic response of human mesenchymal stem cells in gel-nanofibrous environment (IBEC), as well as, on the development of new scaffolds (UPV) and their uploading with growth factors (MLU), the work performed within FIBROGELNET project on the osteogenic differentiation of hMSCs on 2D and 3D constructs is still fairly weak. It is mostly due to the absent cooperation of GENEKAM where most of this work was planned. It influenced also the implementation of the core EuroNanoMed project and was the main reason for asking the suspension of GENEKAM from the project.

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Life Sciences
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