Genetically optimized amyloglucosidase/starch composite for sustained glucose release to enhance mesenchymal stromal cell survival and function in bone defects – GLUCO-BOOST

The GLUCOBOOST project aims to improve the efficiency of cell-based therapy for the repair of large bone defects. Its objective is to overcome a major obstacle in bone tissue engineering: the rapid loss of mesenchymal stromal cells (MSCs) after implantation, when they are exposed to a nutrient-poor environment before sufficient vascularization is restored. Previous work by the B3OA laboratory has shown that MSCs can survive under severe hypoxic conditions, provided that their glucose requirements are met. GLUCOBOOST builds on this observation to develop a metabolic-support strategy specifically tailored to preclinical bone regeneration.

The project is based on a formulation combining particles of a natural polysaccharide, used as a compact carbohydrate reservoir, with a glucoamylase released in a controlled manner from biodegradable PLGA microspheres. The aim is to progressively convert this carbohydrate reservoir into glucose in the vicinity of transplanted MSCs, thereby supporting their viability and repair-related functions over several weeks.

GLUCOBOOST is structured around five complementary tasks: (i) project coordination; (ii) selection and production of the glucoamylase, together with its encapsulation in biodegradable microspheres; (iii) selection and production of natural polysaccharide particles; (iv) in vitro evaluation of encapsulated natural polysaccharide/glucoamylase combinations; and (v) in vivo validation of the selected formulation. The formulations will be assessed for their ability to preserve MSC viability and functionality.

The specificity of GLUCOBOOST lies in its focused preclinical trajectory. After an in vitro optimization phase, the best formulation will be tested in an ectopic rat model and then validated in an orthotopic segmental bone defect model in sheep. Ultimately, GLUCOBOOST aims to mature a therapeutic strategy for the reconstruction of large bone defects, supported by robust preclinical validation.