title: Adipose stem cell tissue-engineered construct used to treat large anterior mandibular defect: a case report and review of the clinical application of good manufacturing practice-level adipose stem cells for bone regeneration.
abstract: OBJECTIVE
  Large mandibular resection defects historically have been treated using autogenous bone grafts and reconstruction plates. However, a major drawback of large autogenous bone grafts is donor-site morbidity.
  
  
  METHODS
  This report describes the replacement of a 10-cm anterior mandibular ameloblastoma resection defect, reproducing the original anatomy of the chin, using a tissue-engineered construct consisting of β-tricalcium phosphate (β-TCP) granules, recombinant human bone morphogenetic protein-2 (BMP-2), and Good Manufacturing Practice-level autologous adipose stem cells (ASCs). Unlike prior reports, 1-step in situ bone formation was used without the need for an ectopic bone-formation step. The reconstructed defect was rehabilitated with a dental implant-supported overdenture. An additive manufactured medical skull model was used preoperatively to guide the prebending of patient-specific hardware, including a reconstruction plate and titanium mesh. A subcutaneous adipose tissue sample was harvested from the anterior abdominal wall of the patient before resection and simultaneous reconstruction of the parasymphysis. ASCs were isolated and expanded ex vivo over the next 3 weeks. The cell surface marker expression profile of ASCs was similar to previously reported results and ASCs were analyzed for osteogenic differentiation potential in vitro. The expanded cells were seeded onto a scaffold consisting of β-TCP and BMP-2 and the cell viability was evaluated. The construct was implanted into the parasymphyseal defect.
  
  
  RESULTS
  Ten months after reconstruction, dental implants were inserted into the grafted site, allowing harvesting of bone cores. Histologic examination and in vitro analysis of cell viability and cell surface markers were performed and prosthodontic rehabilitation was completed.
  
  
  CONCLUSIONS
  ASCs in combination with β-TCP and BMP-2 offer a promising construct for the treatment of large, challenging mandibular defects without the need for ectopic bone formation and allowing rehabilitation with dental implants.
authors: Department of Oral and Maxillofacial Surgery, University of Oulu, Oulu, Finland. george.sandor@uta.fi
authors: George K
authors: GK
authors: Sándor
authors: Veikko J
authors: VJ
authors: Tuovinen
authors: Jan
authors: J
authors: Wolff
authors: Mimmi
authors: M
authors: Patrikoski
authors: Jari
authors: J
authors: Jokinen
authors: Elina
authors: E
authors: Nieminen
authors: Bettina
authors: B
authors: Mannerström
authors: Olli-Pekka
authors: OP
authors: Lappalainen
authors: Riitta
authors: R
authors: Seppänen
authors: Susanna
authors: S
authors: Miettinen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000564:Ameloblastoma / Q000601:surgery*; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use; D001860:Bone Plates; D001861:Bone Regeneration / Q000502:physiology; D018786:Bone Substitutes / Q000627:therapeutic use; D002130:Calcium Phosphates / Q000627:therapeutic use; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D015921:Dental Implants; D019094:Dental Prosthesis, Implant-Supported; D003828:Denture, Overlay; D003829:Denture, Partial; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008339:Mandibular Neoplasms / Q000601:surgery*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000601:surgery; D016348:Osseointegration / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D019651:Plastic Surgery Procedures / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology; D013526:Surgical Mesh; D023822:Tissue Engineering / Q000295:instrumentation* / Q000592:standards; D054457:Tissue Scaffolds; D016212:Transforming Growth Factor beta / Q000627:therapeutic use
chemical_list: D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D002130:Calcium Phosphates; D015921:Dental Implants; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C485817:beta-tricalcium phosphate; C499469:recombinant human bone morphogenetic protein-2