Based on our preclinical and pilot clinical results on use of multipotent mesenchymal stem/stromal cells (MSCs) in traumatology, our aim was to develop 3D tissue-engineered bone equivalent (3D-TEBE) technology for restoration of AVN and bone defects both in civil patients and combat related casualties.
Methods. To fabricate 3D-TEBE we used devitalized allogeneic/xenogeneic bone (blocks and chips) seeded with autologous cultured cells: bone marrow-derived MSCs alone or in mix with periosteum progenitor cells (PPCs, 3:1), or with PPCs and peripheral blood endothelial progenitor cells (EPCs, 3:1:1) depending on bone defect size. Quality assurance of cell seeded 3D-TEBE was done via combined staining with FDA/PI and histological analysis. New bone formation was assessed by the radiographic examination.
Results. Eighteen patients had the AVN III/IV by Steinberg, 11 of them had cystic bone reconstruction sites. In 8 patients, AVN corresponded to stage IV/V with subchondral fracture and deformation of the femoral head (26 patients in total). In AVN patients bone structure restoration was observed in 94.4% and endoprosthesis surgery was no more actual for 90.9%. Bone integrity was successfully restored in 39 combat related casualties (42 critical sized bone defects). FDA/PI staining, and histological analysis of 3D-TEBE samples showed their regular seeding with viable cells. Histological analysis of 3D-TEBE biopsies 3 months after transplantation showed their intensive remodeling and immature bone tissue formation.
Conclusions. The 3D-TEBE transplantation is able to restore bone integrity and greatly reduce, as compared with conventional cure methods, patient’s rehabilitation period.