Osteoinductive moldable and curable bone substitutes based on collagen, bmp-2 and highly porous polylactide granules, or a mix of hap/β-tcp

In dentistry, maxillofacial surgery, traumatology, and orthopedics, there is a need to use osteoplastic materials that have not only osteoinductive and osteoconductive properties but are also convenient for use. In the study, compositions based on collagen hydrogel were developed. Polylactide granules (PLA) or a traditional bone graft, a mixture of hydroxyapatite and β-tricalcium phosphate (HAP/β-TCP), were used for gel filling to improve mechanical osteoconductive properties of compositions. The mechanical tests showed that collagen hydrogels filled with 12 wt% highly porous PLA granules (elastic modulus 373 ± 55 kPa) or 35 wt% HAP/β-TCP granules (elastic modulus 451 ± 32 kPa) had optimal manipulative properties. All composite components were cytocompatible. The cell’s viability was above 90%, and the components’ structure facilitated the cell’s surface adhesion. The bone morphogenetic protein-2 (BMP-2) provided osteoinductive composition properties. It was impregnated directly into the collagen hydrogel with the addition of fibronectin or inside porous PLA granules. The implantation of a collagen hydrogel with BMP-2 and PLA granules into a critical-size calvarial defect in rats led to the formation of the most significant volume of bone tissue: 61 ± 15%. It was almost 2.5 times more than in the groups where a collagenfibronectin hydrogel with a mixture of HAP/β-TCP (25 ± 7%) or a fibronectin-free composition with porous PLA granules impregnated with BMP-2 (23 ± 8%) were used. Subcutaneous implantation of the compositions also showed their high biocompatibility and osteogenic potential in the absence of a bone environment. Thus, the collagen-fibronectin hydrogel with BMP-2 and PLA granules has optimal biocompatibility, osteogenic, and manipulative properties. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Vasilyev A.V. 1, 2, 6, 7 , Kuznetsova V.S.1, 2 , Bukharova T.B.1 , Osidak E.O.3 , Grigoriev T.E.5, 8 , Zagoskin Y.D.5 , Nedorubova I.A.1 , Domogatsky S.P.3, 4 , Babichenko I.I. 2, 6 , Zorina O.A.2, 7 , Kutsev S.I.1 , Chvalun S.N.5 , Kulakov A.A.2 , Losev F.F.2, 7 , Goldshtein D.V. 1
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  • 1 Research Centre for Medical Genetics, Moskvorechye st., 1, Moscow, 115478, Russian Federation
  • 2 Central Research Institute of Dental and Maxillofacial Surgery, Timur Frunze st., 16, Moscow, 119021, Russian Federation
  • 3 Imtek Ltd, 3rd Cherepkovskaya st., 15a, Moscow, 121552, Russian Federation
  • 4 Federal State Budgetary Institution National Medical Research Center of Cardiology Ministry of Health of the Russian Federation, 3rd Cherepkovskaya st., 15a, Moscow, 121552, Russian Federation
  • 5 NRC “Kurchatov Institute”, 1, Akademika Kurchatova pl, Moscow, 123182, Russian Federation
  • 6 Department of Pathological Anatomy, Peoples’ Friendship, University of Russia (RUDN University), 6 Miklukho-Maklaya st, Moscow, 117198, Russian Federation
  • 7 I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, 119991, Russian Federation
  • 8 Moscow Institute of Physics and Technology (National Research University), 9 Institutskiy per., Dolgoprudny, Moscow, 141701, Russian Federation
BMP-2; Collagen; Fibronectin; HAP/β-TCP; Hydrogel; Osteoinduction; Polylactide
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