title: Engineering injectable bone using bone marrow stromal cell aggregates.
abstract: With the increasing popularity of minimally invasive surgery, to develop an injectable bone would be highly preferable for the repair of bone nonunions and defects. However, the use of dissociated cells and exogenous carriers to construct injectable bone faces several drawbacks. To circumvent these limitations, we first harvested a cell sheet from rabbit bone marrow stromal cells using a continuous culture method and a scraping technique. The obtained sheet was then cut into fragments of multicellular aggregates, each of which was composed of a certain number of cells, extracellular matrix, and intercellular connections. The aggregates showed apparent mineralization properties, high alkaline phosphatase activity, increased osteocalcin content, and upregulated bone markers, implying their in vitro osteogenic potential. Then, serum-free medium (the control group), dissociated cell suspension (the cell group), and suspension of multicellular aggregates (the aggregate group) were injected subcutaneously on the back of the nude mice to evaluate ectopic bone formation. The results revealed that the aggregate group showed significantly larger and denser bone at the injection sites than the cell group, whereas bone formation did not occur in the control group. Additionally, when injecting them locally into the mandibular fracture gap of delayed healing in a rabbit model, we observed the most improved bone healing in the aggregate group. More cells survive and retain at the injection sites in the aggregate group than that in the cell group postoperatively. Our study indicates that the multicellular aggregates might be considered a promising strategy to generate injectable bone tissue and improve the efficacy of cell therapy.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Lanzhou, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Ma
authors.forename: Cuiping
authors.initials: C
authors.lastname: Zhong
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.forename: Yanpu
authors.initials: Y
authors.lastname: Liu
authors.forename: Fulin
authors.initials: F
authors.lastname: Chen
authors.forename: Jianxue
authors.initials: J
authors.lastname: Li
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhao
authors.forename: Tianqiu
authors.initials: T
authors.lastname: Mao
authors.forename: Liling
authors.initials: L
authors.lastname: Ren
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000201:enzymology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology / Q000502:physiology*; D002449:Cell Aggregation; D048430:Cell Shape; D005786:Gene Expression Regulation; D020007:Implants, Experimental; D007267:Injections; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D011817:Rabbits; D017154:Stromal Cells / Q000166:cytology / Q000201:enzymology; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D015675:Osteocalcin; D000469:Alkaline Phosphatase