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Development of new materials for reconstructive surgery is one of the key problems among the priority scientifi areas of rehabilitation, regenerative and adaptive medicine. The use of non-resorbed implantable materials is required to replace large bone defects. Promising in this regard are such synthetic materials as ultrahigh-molecular polyethylene (UHMWPE) and polyetheretherketone (PEEK). To improve the fusion of implants with bone tissue, the possibility of their joint application with recombinant proteins having osteogenic properties is relevant. We used porous variants of UHMWPE and PEEK activated by hydroxylapatite (HA) introduced into their structure in combination with recombinant BMP-2, erythropoietin or both proteins to study osteogenicity in the model of cranial critical-sized defects (CSD) regeneration in mice. 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. Both recombinant proteins are capable to spontaneous sorption on hydroxylapatite (HA). The study was carried out on 45 outbred male ICR (CD-1) mice of 38-47 days old. Animals were distributed into 9 groups, 5 mice per group. UHMWPE/HA and PEEK/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 CSD were filed with the UHMWPE/HA and PEEK/HA disks (respectively); in groups 4, 5 CSD were filed with disks containing rhBMP-2; in groups 6, 7 CSD were filed with disks containing erythropoietin; fially, in groups 8, 9 CSD were filed with disks containing both rhBMP-2 and erythropoietin. Tomography was carried out on 0, 3, 6 and 9 weeks postsurgery; eutanasia and histomorphometry were performed on 60 day after surgery. According to the results of tomography and histological analysis all implanted biocomposites demonstrated their high biocompatibility. The addition of rhBMP-2 to the scafflds resulted in significant osteogenic effct and formation of large mineralization areas within 3 weeks after surgery. The addition of erythropoietin led to an increase in the quality of the newly formed bone tissue, as well as, in some cases, to an increase in the amount of mineralized bone. This work was supported by the Russian Science Foundation (Grant No. 16-15-00133).