RESEARCH ARTICLE


Bone Defect Regeneration by a Combination of a β-Tricalcium Phosphate Scaffold and Bone Marrow Stromal Cells in a Non-Human Primate Model



Tomokazu Masaoka1, 2, Toshitaka Yoshii2, Masato Yuasa2, Tsuyoshi Yamada2, 3, Takashi Taniyama2, Ichiro Torigoe2, Kenichi Shinomiya2, Atsushi Okawa2, 3, 4, Sadao Morita1, Shinichi Sotome2, 5, *
1 Department of Rehabilitation Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
2 Department of Orthopaedic and Spinal Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
3 Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan
4 Hard Tissue Genome Research Center, Tokyo Medical and Dental University, Tokyo, Japan
5 Department of Orthopaedic Research and Development, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan


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© Masaoka et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Orthopaedic Research and Development, Graduate School, Tokyo Medical and Dental University 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Tel: 81-3-5803-5272; Fax: 81-3-5803-5272; Email: sotome.orth@tmd.ac.jp


Abstract

Background:

Reconstruction of large bone defects is a great challenge in orthopedic research. In the present study, we prepared composites of bone marrow-derived stromal cells (BMSCs) and β-tricalcium phosphate (β-TCP) with three novel aspects: proliferation of BMSCs with continuous dexamethasone treatment, cell loading under low pressure, and use of autologous plasma as the cell loading medium. The effectiveness of the resulting composite for large bone-defect reconstruction was tested in a non-human primate model, and the bone union capability of the regenerated bones was examined.

Materials and Methods:

Primary surgery: Bone defects (5 cm long) were created in the left femurs of nine cynomolgus monkeys with resection of the periosteum (five cases) or without resection (four cases), and porous β-TCP blocks were transplanted into the defects. Secondary surgery: Bone marrow aspirates harvested from seven of the nine monkeys were cultured with dexamethasone, and BMSCs were obtained. BMSCs were suspended in autologous plasma and introduced into a porous β-TCP block under low-pressure conditions. The BMSC/β-TCP composites were transplanted into bone defects created at the same sites as the primary surgery. Bone union evaluation: Five regenerated femurs were shortened by osteotomy surgery 8 to 15 months after transplantation of the β-TCP/BMSC composites, and bone union was evaluated radiographically.

Results:

After the primary surgery and treatment with β-TCP alone, one of the five periosteum-resected monkeys and two of the four periosteum-preserved monkeys exhibited successful bone reconstruction. In contrast, five of the seven cases treated with the β-TCP/MSC composite showed successful bone regeneration. In four of the five osteotomy cases, bone union was confirmed.

Conclusion:

We validated the effectiveness of a novel β-TCP/BMSC composite for large bone defect regeneration and confirmed the bone union capability of the regenerated bone.

Keywords: Bone marrow-derived stromal cells, bone regeneration, long bone defect, non-human primate, tissue engineering, β-tricalcium phosphate.