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The golden standard among materials used in bone surgery is an autologous bone that has high osteoinductive properties and safety of use. Its use is associated with a number of disadvantages associated with a limited amount of material and additional trauma to the patient. A promising solution to this problem is the development of new materials that have osteoinductive properties due to the presence of biologically active components. Choosing a safe carrier that provides a prolonged effect of bone growth stimulants is an urgent task of modern traumatology and orthopedics. The synthetic materials possessing the required properties are, in particular, nonresorbable ultrahigh-molecular weight polyethylene (UHMWPE) and polyetheretherketone (PEEK), as well as resorbable polylactide (PLA). We used porous variants of UHMWPE, PEEK and PLA activated by hydroxylapatite (HA) introduced into their structure in combination with recombinant BMP-2, erythropoietin (EPO) or both proteins to study osteogenicity in the model of cranial critical-sized defects (CSD) regeneration in mice. The recombinant proteins used were BMP-2 and EPO with additional protein domains providing improvement of solubility and ability to self-induced binding to the carrier. Both recombinant proteins are capable to spontaneous sorption on hydroxyapatite (HA). The study was carried out on 100 outbred male ICR (CD-1) mice of 38-47 days old. Animals were distributed into 10 groups, 10 mice per group. UHMWPE/HA, PEEK/HA and 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 groups 2, 3, 4 CSD were filled with the UHMWPE/HA, PEEK/HA and PLA/HA disks (respectively); in groups 5, 6, 7 CSD were filled with disks containing BMP-2; in groups 8, 9, 10 CSD were filled with disks containing both BMP-2 and EPO. Tomography was carried out on 0, 3 and 6 weeks post-surgery; euthanasia and histomorphometry were performed on 42 day after surgery. According to the results of tomography and histological analysis all implanted biocomposites demonstrated high biocompatibility. The addition of rhBMP-2 to different scaffolds resulted in significant osteogenic effect and formation of large mineralization areas within 3 weeks after surgery. The lowest volume of new bone tissue was demonstrated in the group with PEEK/HA possibly due to the difficulty of sprouting blood vessels inside the implant. The effect of erythropoietin addition is maximal in the case of PLA/HA possibly due to the resorbable properties of the carrier. This work was supported by the Russian Science Foundation (Grant No. 16-15-00133).