Conception d'hydrogels injectables à base d'un exopolysaccharide marin pour l'ingénierie ostéo-articulaire
(Projet-ANR-22-CE52-0005)

Octobre 2022 - Février 2027

Partenaire IMN du projet : Stéphane CUENOT  (équipe PMN)

Coordinateur :
Institut Francais de Recherche pour l'Exploitation de la Mer (IFREMER Nantes)
Partenaires :
Inserm RMeS Nantes

Personnels IMN impliqués :
Jean LE BIDEAU (PR UNIV)

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Osteochondral injuries remain an unmet medical need with huge clinical expectations, since untreated they often evolve to osteoarthritis and ultimately lead to total joint replacement. Current surgical treatments, including cell-based therapies, such as autologous chondrocyte implantation allow only a partial functional recovery. To overcome the drawbacks related to these techniques (limited cell availability, donor site morbidity, logistical and regulatory complexity), alternative cell-free approaches have recently been considered with a growing interest. In this context, SmartIEs project aims to explore a cell-free strategy to repair osteochondral lesions by developing a smart hydrogel scaffold that will very efficiently recruit regenerative progenitor cells and stimulate their differentiation into appropriate cell lineages capable of regenerating both cartilage and subchondral bone. This strategy will be carried out with two main objectives. In the first objective, an injectable thermoresponsive hydrogel based on a marine bacterial exopolysaccharide (EPS) endowed with glycosaminoglycan (GAG)-mimetic properties will be developed. The thermoresponsive property will arise from the poly(N-isopropylacrylamide) (pNIPAm) grafted on the polysaccharide backbone. By loading this hydrogel with EPS-based microgels encapsulating two growth factors (GFs), either Transforming Growth Factor-b1 (TGF-b1) or Bone Morphogenetic Protein-2 (BMP-2), a bifunctional hydrogel will be formed. In vivo, progenitor cells will then migrate through this deformable, fast relaxing hydrogel and differentiate by interacting with appropriate GFs to simultaneously promote cartilage (TGF-β1) and bone (BMP-2) regeneration. The second objective will consist in the biological evaluation of the bifunctional hydrogel containing GF-loaded microgels to repair osteochondral defects in a relevant large animal model.