title: Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds.
abstract: OBJECTIVE
  In pediatric neurosurgery, decompressive craniectomy and correction of congenital cranial anomalies can result in major cranial defects. Corrective cranioplasty for the repair of these critical-sized defects is not only a cosmetic issue. The limited availability of suitable autogenous bone and the morbidity of donor site harvesting have driven the search for new approaches with biodegradable and bioactive materials. This study aimed to assess the healing of rabbit calvarial critical-sized defects filled with osteogenic material, either with bioactive glass scaffolds or tricalcium phosphate granules in various combinations with adipose stem cells or bone marrow stem cells, BMP-2, BMP-7, or VEGF to enhance osteogenesis.
  
  
  METHODS
  Eighty-two bicortical full thickness critical-sized calvarial defects were operated. Five defects were left empty as negative control defects. The remaining 77 defects were filled with solid bioactive glass scaffolds or tricalcium phosphate granules seeded with adipose or bone marrow derived stem cells in combination with BMP-2, BMP-7, or VEGF. The defects were allowed to heal for 6 weeks before histologic and micro-CT analyses.
  
  
  RESULTS
  Micro-CT examination at the 6-week post-operative time point revealed that defects filled with stem cell-seeded tricalcium phosphate granules resulted in new bone formation of 6.0 %, whereas defects with bioactive glass scaffolds with stem cells showed new bone formation of 0.5 to 1.7 %, depending on the growth factor used.
  
  
  CONCLUSIONS
  This study suggests that tricalcium phosphate granules combined with stem cells have osteogenic potential superior to solid bioactive glass scaffolds with stem cells and growth factors.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Oulu University Hospital and Medical Research Center, University of Oulu, Oulu, Finland.
authors.forename: Olli-Pekka
authors.initials: OP
authors.lastname: Lappalainen
authors.affiliation: Research Group of Medical Imaging, Physics and Technology, Infotech Doctoral Program, University of Oulu, Oulu, Finland.
authors.forename: Sakari
authors.initials: S
authors.lastname: Karhula
authors.affiliation: Department of Diagnostic Radiology, University of Oulu, Oulu, Finland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Haapea
authors.affiliation: BioMediTech, Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Kyllönen
authors.affiliation: BioMediTech, Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland.
authors.forename: Suvi
authors.initials: S
authors.lastname: Haimi
authors.affiliation: BioMediTech, Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Miettinen
authors.affiliation: Research Group of Medical Imaging, Physics and Technology, Infotech Doctoral Program, Department of Diagnostic Radiology, Medical Research Center, University of Oulu, Oulu, Finland.
authors.forename: Simo
authors.initials: S
authors.lastname: Saarakkala
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Oulu University Hospital, Oulu, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Korpi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Oulu University Hospital and Medical Research Center, University of Oulu, Oulu, Finland.
authors.forename: Leena P
authors.initials: LP
authors.lastname: Ylikontiola
authors.affiliation: Department of Children and Adolescents, Division of Pediatric Surgery, Oulu University Hospital, Medical Research Center, PEDEGO Research Center, University of Oulu, Oulu, Finland.
authors.forename: Willy S
authors.initials: WS
authors.lastname: Serlo
authors.affiliation: Department of Oral and Maxillofacial Surgery, Oulu University Hospital and Medical Research Center, University of Oulu, Oulu, Finland. george.sandor@oulu.fi.|BioMediTech, Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland. george.sandor@oulu.fi.
authors.forename: George K
authors.initials: GK
authors.lastname: Sándor
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000000981:diagnostic imaging / Q000628:therapy*; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage; D055419:Bone Morphogenetic Protein 7; D004195:Disease Models, Animal; D006801:Humans; D006882:Hydroxyapatites / Q000627:therapeutic use*; D036341:Intercellular Signaling Peptides and Proteins / Q000627:therapeutic use*; D008297:Male; D011817:Rabbits; D013234:Stem Cells / Q000502:physiology*; D054457:Tissue Scaffolds; D015898:Tomography Scanners, X-Ray Computed; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C525718:BMP2 protein, human; C525819:BMP7 protein, human; D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; C558777:BoneCeramic; D006882:Hydroxyapatites; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A
keywords: Bone healing; Cranial defect; Micro-CT; Stem cells