Non-viral gene transfer in hydrogel matrices with octacalcium phosphate microgranules in optimization of reparative osteogenesis

There is a strong unmet need for bone grafts and substitutes combining osteoinductive capacities and biophysical properties for using them in minimally invasive surgical interventions. We have developed three variants of injectable gene-activated bone substitutes containing three components: octacalcium phosphate microgranules (OCP), plasmid DNA delivering the gene of vascular endothelial growth factor, and one of the hydrogels based on sodium alginate, type I collagen, and hyaluronic acid. The molecules of the gene constructs were contained both in the hydrogel and on the surface of the OCP microgranules. In the model of a critical-sized bone defect in rabbit parietal bone, we found that all the gene-activated hydrogels contributed to bone tissue regeneration, however, the largest amount of newly formed bone, including those in the central part of the defect, was detected in the groups with gene-activated materials based on hyaluronic acid and collagen. Thus, the developed materials can be considered as candidates for medical devices, but additional studies are required to assess the dose-depended effect and optimize the materials composition.