Nano-reinforced hydrogel for cartilage regenerative medicine and tissue engineering – HYCAR

Aqueous formulations of covalent (chemical) and ionic (physical) hydrogels are made compatible and characterized from a rheological point of view and for their mechanical and diffusion properties. Some selected formulations serve as substrates for the culture of cell lines and mesenchymal stem cells to follow their biocompatibility and their potential to allow the differentiation of these cells into cartilage.

The first results of our work show that we can combine these two systems hydrogels, they are compatible. Under certain conditions they perform a double interconnected network dramatically improving the mechanical properties of the whole.
The first results show a good biocompatibility of cell viability in three dimensions to a threshold beyond which the viability decreases significantly. We do not currently know whether this result is linked to nanoparticles as such or whether it is down nutrients and oxygen that is responsible for this trend.

Perspectives are important in the field of tissue engineering because it could control many parameters of scaffolds for stem cells to direct them towards a specific cell type for regenerative medicine tissue.

Oral Communications: WBC 2012
Poster Communication: TERMIS 2012
No publications or patents.

Today regenerative medicine is moving towards the development of less and less invasive surgical techniques with the objective of reducing morbidity and the duration of hospitalization. This quest for minimally-invasive surgery has motivated the development of injectable matrices for cartilage tissue engineering. Once implanted, these injectable matrices must also be able to harden, acquire the desired form, and present mechanical properties in close to the tissue to be repaired. Polymers with high viscosity can be used to produce hydrogels by physical , ionic or covalent crosslinking. In this case, they form true 3D macromolecular networks comparable to the extracellular matrix (ECM) of tissues of our body. Our current research area is the regeneration of articular cartilage tissue whose intrinsic regeneration properties are extremely low. Our goal is to develop biopolymers-based hydrogels for tissue engineering in combination with autologous chondrogenic cells for cartilage regeneration. Currently hydrogels for encapsulating living cells such as HPMC-Si we have developed, have low mechanical properties (10 to 20 times lower than those of cartilage). We know from the work of Discher that mesenchymal stem cells (MSC) are able to "touch and feel" the stiffness of the matrix with which they are in contact and that this contributes to their commitment to a specific lineage. Our hydrogels are adapted to the repair of small cartilage defects but are likely too fragile for the regeneration of large cartilage defects. It seems therefore necessary to improve their rigidity and their mechanical properties while keeping them compatible with the viability of MSC, whose regenerative properties of cartilage are today well acknowledged. Our approach is based on the reinforcement of hydrogels with nano particles of silicate and modeling micromechanical behavior and diffusion of molecules in these hydrogel/MSC hybrid constructs . To address this issue we will divide our work into five tasks including 4 operational tasks: the formulation and design of nano-reinforced hydrogel, physicochemical characterization, in vitro biocompatibility and finally the in vivo biofunctionality . This work at the interface of materials chemistry and biology will be done by gathering the expertise of two partners the university of Maine, CNRS (UMR PCI 6120), a specialist in Soft Materials and hydrogels and a Laboratory INSERM from the Nantes University (LIOAD UMRS 791), with a strong background in the regeneration of cartilage tissue. Our hybrid constructs (reinforced hydrogels/MSC) will allow us to understand the influence of hydrogel construct parameters on the behavior of MSC in a synthetic three-dimensional environment.. These parameters are the density and viscoelasticity of macromolecular mesh, the diffusion properties (gas and nutrients) and the existence of barriers, the mobility of water and macromolecules in the network, hydrophilicity, adhesion sites for the proteins, the existence of specific microenvironments. The role of each of these parameters on the growth, mobility and MSC differentiation will allow us to develop strategies for the design of appropriate extracellular matrix for specific indications of cartilage tissue engineering. Finally we will check on animal models (ONIRIS, National Veterinary School of Nantes) the relevance of our concept in the repair of knee joint in rabbit and horse whose joint diseases, close to humans, will benefit from this strategy of regenerative medicine. .