title: The regeneration and augmentation of bone with injectable osteogenic cell sheet in a rat critical fracture healing model.
abstract: Limitations in the current treatment strategies make cases with compromised bone healing challenging clinical problems. Osteogenic cell sheets (OCSs), fabricated from rat bone marrow stromal cells (BMSCs), contain enriched osteoblasts and extracellular matrix. Here, we evaluated whether the minimally invasive percutaneous injection of OCSs without a scaffold could be used as a treatment to increase bone regeneration in a critical fracture healing model. Critical fracture healing model was created in the femora of 60 male Fischer 344 inbred rats using marrow ablation and periosteal removal. The rats were then randomly divided into two groups. Six hours after fracture, one group received an injection of OCSs (OCS group), while the second group was injected with phosphate-buffered saline (PBS) (control group). Fracture healing was evaluated using radiological, histological, micro-computed tomography (CT) and biomechanical analyses. The radiological and histological evaluations demonstrated enhanced bone regeneration in the OCS group compared with that in the control group. By 12 weeks, the hard callus had been remodelled via recorticalization in the OCS group. By contrast, no fracture union was found in the rats in the control group. Biomechanical testing revealed a significantly higher maximum bending load in the OCS group compared with that in the control group. The results of the present study demonstrate that the injection of entire OCSs can enhance bone regeneration and lead to bony union in a critical fracture healing model. Therefore, this procedure offers a minimally invasive technique to promote hard tissue reconstruction and, in particular, bone repair strategies for cases with compromised bone healing.
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Electronic address: tk-shimi@naramed-u.ac.jp.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine, Kashihara, Nara 634-8521, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Akahane
authors.affiliation: Department of Biomedical Engineering, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Morita
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Omokawa
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakano
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kira
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Onishi
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inagaki
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Okuda
authors.affiliation: Department of Artificial Joint and Regenerative Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawate
authors.affiliation: Department of Orthopedic Surgery, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001861:Bone Regeneration / Q000187:drug effects*; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000473:pathology*; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology*; D017102:Fracture Healing / Q000187:drug effects*; D005599:Fractures, Ununited / Q000000981:diagnostic imaging / Q000473:pathology*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D010006:Osteoblasts; D011859:Radiography; D051381:Rats; D011916:Rats, Inbred F344; D015203:Reproducibility of Results
keywords: Bone marrow stromal cell; Bone regeneration; Bone tissue-engineering; Extracellular matrix; Fracture healing; Injectable bone; Nonunion; Osteogenic cell sheet