Laser-assisted stem cells bio-printing for regenerative medecine – ICELARE

The aim of the interdisciplinary project ICELARE is to combine cell biology with advanced laser-based techniques (laser-assisted printing, laser surface structuring, laser nanoparticle fabrication) for tissue engineering and regenerative medicine. The objective is to create and study 2D/3D microenvironments that best mimic the complexity and in vivo architecture of tissues in order to understand the interaction of cells with the environment in which they develop. In particular, we target the optimization of muscle cell differentiation and the formation of active neuromuscular junctions. The success of the project is based on the complementary expertise of the two laboratories involved, the Lasers, Plasmas and Phonic Processes Laboratory in the field of laser processes and the Marseille Medical Genetics Centre in the field of stem cells applied to muscle differentiation.
The contractile function of the muscle can be modified in different situations such as traumas or certain diseases. If the muscle has good regenerative capacities, this faculty is limited when the trauma is too great. There is a great demand for the development of effective protocols to produce reproducible and standardized cellular models for pathologies affecting the muscles as well as the production of therapeutic grafts for the repair of functional tissues. One solution is the construction of muscle tissue in vitro and ex vivo but this is highly dependent on the ability to recreate the cellular complexity of the tissue to ensure the survival, vascularization and functional maturation of the grafted cells.
The emergence of induced pluripotent stem cell technology, and their capacity for unlimited proliferation in culture as well as their potential for differentiation into all cell types, has led to the development of new therapies. But in the case of muscle cells the level of differentiation and tissue maturation remains limited and experimental development is still needed to obtain sufficiently differentiated cells. Until now, advances in muscle repair medicine and the modelling of acquired or congenital muscle pathologies using these approaches have been hampered by the lack of a satisfactory method for generating muscle cells from human stem cells.
One way to improve these processes is to take advantage of tissue engineering. Thus, the ability to accurately position cells in complex 2D/3D models is proving to be of critical importance for the optimization and validation of ex vivo differentiation approaches and the development of new controlled and reproducible models. In addition, contact topography guidance in terms of micro/nano scale as well as the influence of nanoparticles in the culture medium are emerging parameters for successful differentiation and regeneration. This is a major challenge for future advances in tissue engineering, especially for effective on-site regenerative medicine. Within the framework of ICELARE, 3 processes will be implemented (bioprinting, surface structuration and addition of nanoparticules) with the assistance of pulsed lasers, which gives each of them clear advantages compared to traditional methods: clean method (no solvents or chemical additives), photonic process (no disturbances due to moving mechanical parts, no clogging of nozzles, very important precision and control), digital control...
The expected results would represent an important breakthrough for biomedical research and tissue engineering with numerous applications: basic research, regenerative medicine, industrial developments in pharmacology, etc.