Influence of the Degree of Deacetylation of Chitosan and BMP-2 Concentration on Biocompatibility and Osteogenic Properties of BMP-2/PLA Granule-Loaded Chitosan/β-Glycerophosphate Hydrogels

Compositions based on chitosan/β-glycerophosphate hydrogels with highly porous polylactide granules can be used to obtain moldable bone graft materials that have osteoinductive and osteoconductive properties. To eliminate the influence of such characteristics as chain length, degree of purification, and molecular weight on a designed material, the one-stock chitosan sample was reacetylated to degrees of deacetylation (DD%) of 19.5, 39, 49, 55, and 56. A study of the chitosan/β-glycerophosphate hydrogel with chitosan of a reduced DD% showed that a low degree of deacetylation increased the MSCs (multipotent stromal cells) viability rate in vitro and reduced the leukocyte infiltration in subcutaneous implantation to Wistar rats in vivo. The addition of 12 wt% polylactide granules resulted in optimal composite mechanical and moldable properties, and increased the modulus of elasticity of the hydrogel-based material by approximately 100 times. Excessive filling of the material with PLA (polylactide) granules (more than 20%) led to material destruction at a ~10% strain. Osteoinductive and osteoconductive properties of the chitosan hydrogel-based material with reacetylated chitosan (39 DD%) and highly porous polylactide granules impregnated with BMP-2 (bone morphogenetic protein-2) have been demonstrated in models of orthotopic and ectopic bone formation. When implanted into a critical-size calvarial defect in rats, the optimal concentration of BMP-2 was 10 μg/mL: bone tissue areas filled the entire material's thickness. Implantation of the material with 50 μg/mL BMP-2 was accompanied with excessive growth of bone tissue and material displacement beyond the defect. Significant osteoinductive and osteoconductive properties of the material with 10 μg/mL of BMP-2 were also shown in subcutaneous implantation.

Vasilyev A.V. 1, 2, 3 , Kuznetsova V.S.1, 2 , Bukharova T.B.1, 2 , Grigoriev T.E.4, 5 , Zagoskin Y.D.4 , Nedorubova I.A.1, 2 , Babichenko I.I. 2, 3 , Chvalun S.N.4 , Goldstein D.V. 1, 2, 3 , Kulakov A.A.1
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  • 1 Research Centre for Medical Genetics, Moskvorechye st.Moscow 115478, Russian Federation
  • 2 Central Research Institute of Dental and Maxillofacial Surgery, Timur Frunze st., 16Moscow 119021, Russian Federation
  • 3 Institute of Medicine, Peoples' Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya st.Moscow 117198, Russian Federation
  • 4 Akademika Kurchatova pl.Moscow 123182, Russian Federation
  • 5 Moscow Institute of Physics and Technology (National Research University), 9 Institutskiy per. ,DolgoprudnyMoscow 141701, Russian Federation
BMP-2; chitosan; deacetylation degree; osteoinduction; osteoplastic material; porous polylactide granules
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