title: Enhancing bone formation by transplantation of a scaffold-free tissue-engineered periosteum in a rabbit model.
abstract: OBJECTIVE
  The periosteum plays an important role in bone regeneration. However, the harvesting of autogenous periosteum is associated with disadvantages such as donor site morbidity and limited donor sources. This study uses an osteogenic predifferentiated cell sheet to fabricate a scaffold-free tissue-engineered periosteum (TEP).
  
  
  METHODS
  We generated an osteogenic predifferentiated cell sheet from rabbit bone marrow stromal cells (BMSCs) using a continuous culture system and harvested it using a scraping technique. Then, the in vitro characterization of the sheet was investigated using microscopy investigation, quantitative analysis of alkaline phosphatase (ALP) activity, and RT-PCR. Next, we demonstrated the in vivo osteogenic potential of the engineered sheet in ectopic sites together with a porous β-tricalcium phosphate ceramic. Finally, we evaluated its efficiency in treating delayed fracture healing after wrapping the cell sheet around the mandible in a rabbit model.
  
  
  RESULTS
  The engineered periosteum showed sporadic mineralized nodules, elevated ALP activity, and up-regulated gene expression of osteogenic markers. After implantation in the subcutaneous pockets of the donor rabbits, the in vivo bone-forming capability of the engineered periosteum was confirmed by histological examinations. Additionally, when wrapping the engineered periosteum around a mandibular fracture gap, we observed improved bone healing and reduced amounts of fibrous tissue at the fracture site.
  
  
  CONCLUSIONS
  The osteogenic predifferentiated BMSC sheet can act as a scaffold-free TEP to facilitate bone regeneration. Hence, our study provides a promising strategy for enhancing bone regeneration in clinical settings.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Gansu, ChinaDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Shaanxi, ChinaRege Lab of Tissue Engineering, Department of Bioscience, Faculty of Life Science, Northwest University, Shaanxi, ChinaDepartment of Orthodontics, School of Stomatology, Lanzhou University, Gansu, China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Gansu, ChinaDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Shaanxi, ChinaRege Lab of Tissue Engineering, Department of Bioscience, Faculty of Life Science, Northwest University, Shaanxi, ChinaDepartment of Orthodontics, School of Stomatology, Lanzhou University, Gansu, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Gansu, ChinaDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Shaanxi, ChinaRege Lab of Tissue Engineering, Department of Bioscience, Faculty of Life Science, Northwest University, Shaanxi, ChinaDepartment of Orthodontics, School of Stomatology, Lanzhou University, Gansu, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Gansu, ChinaDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Shaanxi, ChinaRege Lab of Tissue Engineering, Department of Bioscience, Faculty of Life Science, Northwest University, Shaanxi, ChinaDepartment of Orthodontics, School of Stomatology, Lanzhou University, Gansu, China.
authors.forename: Fulin
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Gansu, ChinaDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Shaanxi, ChinaRege Lab of Tissue Engineering, Department of Bioscience, Faculty of Life Science, Northwest University, Shaanxi, ChinaDepartment of Orthodontics, School of Stomatology, Lanzhou University, Gansu, China.
authors.forename: Yanpu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Gansu, ChinaDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Shaanxi, ChinaRege Lab of Tissue Engineering, Department of Bioscience, Faculty of Life Science, Northwest University, Shaanxi, ChinaDepartment of Orthodontics, School of Stomatology, Lanzhou University, Gansu, China.
authors.forename: Tianqiu
authors.initials: T
authors.lastname: Mao
authors.affiliation: Department of Oral and Maxillofacial Surgery, Lanzhou General Hospital, Lanzhou Command of PLA, Gansu, ChinaDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Fourth Military Medical University, Shaanxi, ChinaRege Lab of Tissue Engineering, Department of Bioscience, Faculty of Life Science, Northwest University, Shaanxi, ChinaDepartment of Orthodontics, School of Stomatology, Lanzhou University, Gansu, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Ren
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D023421:Models, Animal; D010012:Osteogenesis / Q000502:physiology*; D010521:Periosteum / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods*; D055114:X-Ray Microtomography
chemical_list: D000469:Alkaline Phosphatase