4RDNEBTKSTQDC@TSNKNFNTR!, ,2"RENQ@KSDQDCONRS SQ@TL@SHBQDO@Q@SHUD NRSDNFDMDRHRSQD@SLDMSMNMQ@MCNLHYDCBKHMHB@KSQH@K *V Oksymets1,2, D Zubov3,4, R Vasyliev3,4 & V Klimovytsky1 (MRSHSTSDNE3Q@TL@SNKNFX@MC.QSGNO@DCHBR#NMDSRJ-@SHNM@K,DCHB@K4MHUDQRHSXNE,@WHL&NQJX#NMDSRJ 4JQ@HMD 2 2S@SD(MRSHSTSDNE4QFDMS@MC1DBNUDQX2TQFDQXM@LDC@ESDQ5*&TR@J-@SHNM@K B@CDLXNE,DCHB@K2BHDMBDR NE4JQ@HMD#NMDSRJ4JQ@HMD 3 2S@SD(MRSHSTSDNE&DMDSHB@MC1DFDMDQ@SHUD,DCHBHMD-@SHNM@K B@CDLXNE,DCHB@K2BHDMBDRNE4JQ@HMD"DKK @MC3HRRTD3DBGMNKNFHDR*HDU4JQ@HMD 4 !HNSDBGMNKNFX+@ANQ@SNQX(K@X@1DFDMDQ@SHNM,DCHB@K"NLO@MXHK@X@*HDU4JQ@HMD 1
.AIDBSHUD Post-traumatic reparative osteogenesis condition depends on the energy value of the traumatic agent. The reason for the lack of fracture consolidation in high-energy injuries is bone cell death at a distance from the fracture line and the alteration of osteoreparative mechanisms. MSCs trigger the pathological osteoreparative processes in a chronic bone wound by means of paracrine effects and structural tissue repair, which lead to the formation of bone regenerate. The objectives were to determine the effectiveness of cultured syngeneic BM-MSCs injection for long-term tibia fracture nonunion treatment in animals, and to evaluate the effectiveness of autologous cultured BM-MSC grafting for treatment of altered post-traumatic reparative osteogenesis and bone defects in patients. ,@SDQH@KRLDSGNCR High-energy trauma modeling in Wistar rats; BM-MSC culture; MSC differentiation assays; pathomorphological analysis – hematoxlin and eosin stain; statistical analysis; nonrandomized clinical trial involved 26 patients with longterm high-energy fracture nonunions (19 patients with tibia fractures, seven with femoral fractures) and 12 patients with bone defects. Each patient was subjected to 3.4 ± 0.8 surgical interventions average before MSC grafting; duration of bone integrity alteration was 57.6 ± 15.8 weeks average Bone defects were localized in eight patients in tibia, two patients in the femur, one patient in the humerus and one patient in the heel areas. 1DRTKSRBNMBKTRHNM Animals: by day 10, the BM-MSCs were administered in the intrafragmentary area via injection of 5 × 104 syngeneic cells in suspension to 21 animals. The fractured bone immobilization was maintained in 14 animals (group 1), in seven, the immobilization was removed (group 2). In nine control animals (group 3), 0.5 ml DMEM:F12 medium was injected into the immobilized fracture. By day 7, the abnormal bone fragment mobility was observed in Group 1. pathomorphological analysis revealed the acellular bone areas with osteoclasts and the multiple loci of bone formation de novo. By day 14, the abnormal bone fragment mobility was absent in the fracture area and pathomorphological analysis showed the bone regenerate formation. By day 14 in group 2, the minor abnormal bone fragment mobility was observed. Bone tissue formation close to the bone fracture edges, and the hyaline-like cartilage in the intertrabecular spaces were found. In group 3, the coarse fiber bone was formed to the end of second week. Patients: cultured BM-MSCs transplantation via the injection method was performed in 6 patients with fracture nonunions; via surgery technique in the form of 3D osteoprogenitor transplant in 32 patients, including 12 patients with bone defects. In total, eight out of 12 injured persons possessed scars and ulcers over the bone defect area. In six patients, the tibia defects were combined with soft-tissue defects of the lower leg, which were replaced via displaced nonfree flaps. After a single MSC grafting procedure, positive results were obtained in 37 patients (97.4%). The average consolidation time of bone fragments in patients with fracture nonunions after MSCs transplantation was 21.6 ± 3.3 weeks and was comparable with the consolidation time of closed diaphyseal fractures caused by low-energy trauma (19.7 ± 2.2 weeks). Terms of bone integrity restoring after MSCs transplantation ranged from 3 to 8 months and depended on the type and size of the bone defect (Figure 1) . Clinical trial data revealed that cultured BM-MSC grafting may restore the reparative processes in chronic bone wound and lead to new bone formation.
future science group
Osteoprogenitor transplant grafting
6 weeks H&E, Ă—75
Male, 42 years, subtotal defect of the right calcaneus
future science group