Master 2 Internship
Design of collagen biomaterials for cartilage tissue engineering
Host institution: Laboratoire de Biologie Tissulaire et d’Ingénierie thérapeutique (LBTI)
UMR5305, 7 Passage du Vercors, 69007, Lyon, France
OsteoArticular and Dental Research (ROAD) team
To apply, contact: Jean-Daniel Malcor – email@example.com – 04 72 72 26 19
The repair of damaged tissues following injury represents a major clinical challenge. To address this issue, tissue engineering, which consists in combining cells with biomaterials, is an attractive strategy to trigger the reconstruction of injured tissues. However, this approach is often limited by poor cell-biomaterial interactions. For example, collagen, the main component of the extracellular matrix that naturally provides a structural and biological support for cells, is frequently used in tissue engineering. However, in order to obtain adequate mechanical properties, collagen biomaterials are often crosslinked by treatment with carbodiimides, which chemically modify the native amino acid sequences recognized by collagen-binding receptors. This prevents the retention, function and survival of cells seeded on biomaterials that otherwise possess optimal mechanical properties.
We aim to develop collagen biomaterials that possess both the optimal biological and mechanical properties for cartilage tissue engineering. These biomaterials must have a rigidity that resembles that of healthy cartilage, while promoting the adhesion and function of chondrocytes or mesenchymal stem cells (MSCs). To achieve this goal, we will use collagen-mimetic triple-helical peptides to 1) develop a new crosslinking method that enables the adjustment of biomaterial mechanical properties without modifying the native collagen sequences that are required for its biological role; and 2) restore the appropriate biological signals to collagen biomaterials crosslinked with carbodiimides, using triple-helical peptides to address collagen-binding receptors expressed on cell surfaces.
The candidate will carry out chondrocyte and MSC culture, and seed cells on crosslinked collagen biomaterials. The objective will then be to analyze cell response, in particular cell survival, adhesion and activity, using immunofluorescence, quantitative PCR and western blot techniques. We will especially focus on investigating MSC differentiation on the different collagen substrates.
The candidate will be Master 2 student or equivalent, with a strong background in cell biology and biochemistry. She/he will be willing to work in multidisciplinary lab, on a topic involving chemistry, biology and material science. A great interest for the field of tissue engineering and biomaterials is also essential. Finally, the candidate will be required to work independently, to show initiative and scientific rigor, to analyze and synthesize results, and to demonstrate strong teamwork skills. The starting date is flexible, and is planned for the beginning of 2022.
- J-D. Malcor, D. Bax, S.W. Hamaia, N. Davidenko, S. Best, R. Cameron, R. Farndale, D. Bihan, The synthesis and coupling of photoreactive collagen-based peptides to restore integrin reactivity to an inert substrate, chemically-crosslinked collagen, Biomaterials 85 (2016) 65-77.
- J-D. Malcor, E. Hunter, N. Davidenko, B. Bax, S. Best, R. Cameron, S. Sinha, R. Farndale, Collagen scaffolds functionalized with triple-helical peptides support 3D HUVEC culture, Regenerative Biomaterials 5 (2020) 7 471-481.