ИСТИНА

Polylactide (PLA) is a well-characterized bioresorbable polymer. However, for improvement of fusion with bone tissue, the possibility of joint use with protein factors possessing osteogenic properties is relevant. The task of protein factors’ introducing into polymeric synthetic materials is not easy and requires special technological solutions such as introducing nanoparticles of hydroxyapatite (HA, the main mineral component of bone) into their composition. Polylactide (molecular weight of 110 kg / mol; Ingeo 4032D by Natureworks LLC) in pellet form was used as the main material for the preparation of porous scaffold. Hydroxyapatite (HA needle particles 90 nm in size, Polistom, Moscow) was used as a component that increases the bioactivity of implants. The evaporated salt was used as a pore-forming agent. Solvent casting and salt leaching method was utilized for the preparation of polylactide/HA scaffolds. The resulted porosity was 74%vol. Scanning electron microscopy study of the microstructure of the obtained samples showed the presence of a system of open pores with a size of 300–400 µm and a thickness of the pore wall of 1–2 µm. The recombinant proteins used were rhBMP-2 and erythropoietin proteins with additional protein domains providing improvement of solubility and ability to self-induced binding to the carrier. The study was carried out on 50 outbred male ICR (CD-1) mice of 38-47 days old. Animals were distributed into 5 groups, 10 mice per group. PLA/HA disks of 1.0 (thickness) x 4.0 (diameter) mm with/without bound proteins were sterilized and implanted into 4 mm CSD of mice. In group 1 (control) CSD were empty; in group 2 CSD were filled with the PLA/HA disks; in group 3 CSD were filled with PLA/HA disks containing erythropoietin; in group 4 CSD were filled with PLA/HA disks containing rhBMP-2; in group 5 CSD were filled with PLA/HA disks containing both rhBMP-2 and erythropoietin. Tomography was carried out on 0, 3 and 6 weeks post-surgery; eutanasia and histomorphometry were performed on 42 day after surgery. All implanted materials demonstrated good biocompatibility and no inflammatory reactions. The largest volume of newly formed bone, as well as an increase in the density and size of blood vessels, was observed in the group using both factors. This work was supported by the Russian Science Foundation (Grant No. 16-15-00133).