DHERMIC

Title: Hybrid Elastic Dendrigraft for the Regeneration and the Modeling in Skin Engineering (acronym: DHERMIC) The overriding function of tissue-engineered skin is to restore barrier function to patients in whom this has been severely compromised. Any loss of full-thickness skin of more than four centimeters in diameter will not heal well without a graft. This multidisciplinary science has particularly evolved during the last thirty years to rescue patients with severe burns and in the elderly who is more prone to chronic skin wounds that could degenerate in amputation if not healed. Beside therapeutic applications, tissue engineering offers an alternative to animal experiments for basic research on extracellular matrix/cells interactions and pharmacological concerns. Hence, tissue-engineered skin products are implicated in a wide market at the national, European and even worldwide levels. Dozens of skin substitutes are available, mainly collagen-based matrices, with the same major drawback: they do not reproduce elastic properties of the native tissue. This absence of elasticity is driven by: (i) the ignorance of biological parameters leading to a functional elastogenesis in adult tissues; and (ii) the absence of an adapted supportive matrix to bring a correct cell microenvironment in terms of elasticity and visco-elasticity. The DHERMIC project proposes a very important breakthrough to unlock some of these technological bolts and will provide a new generation of skin bio-substitutes integrating: • An elastic behavior inspired from the human tropoelastin; • A “green”, simple and cheap synthesis process; • Easily adjustable mechanical parameters to mimic different kind of tissues. To achieve this objective, this four-year project will focalize on skin bioengineering by a multidisciplinary approach defining different interconnected workpackages: (WP1) chemistry to establish the hybrid polymer; (WP2) biology to characterize skin cell phenotypes and the scaffold biocompatibility; and (WP3) a functional approach trough biomechanical properties of the scaffold and reconstructed tissues. A fourth workpackage (WP4) will be devoted to applicative researches to test the biomaterial (i) in a wound healing animal model; (ii) as a 3D scaffold to model a genetic disease related to a defective elastogenesis; and (iii) in other tissues. An administrative workpackage (WP0) will ensure the good running and the management of the project. The project achievement relies on strong complementarities between the partners. The two academic laboratories, DyHTIT and LTDS are internationally recognized for their works on elastic fibers biology and skin biomechanics respectively. The private partner COLCOM is a SME and a spin-off of a French laboratory; they have a strong know-how on lysine dendrigraft chemistry which composes the synthetic core of the biomaterial. If successful, the hybrid elastic biomaterial delivered by the consortium will provide dramatic advances in terms of public health by improving severe burns care and age-related chronic wounds healing. Thanks to the in vitro modeling, this new skin substitute will initiate a dynamic research on rare diseases related to connective tissues defects and for which no treatment exists at the present time.