title: GMP-level adipose stem cells combined with computer-aided manufacturing to reconstruct mandibular ameloblastoma resection defects: Experience with three cases.
abstract: BACKGROUND
  The current management of large mandibular resection defects involves harvesting of autogenous bone grafts and repeated bending of generic reconstruction plates. However, the major disadvantage of harvesting large autogenous bone grafts is donor site morbidity and the major drawback of repeated reconstruction plate bending is plate fracture and difficulty in reproducing complex facial contours. The aim of this study was to describe reconstruction of three mandibular ameloblastoma resection defects using tissue engineered constructs of beta-tricalcium phosphate (β-TCP) granules, recombinant human bone morphogenetic protein-2 (rhBMP-2), and Good Manufacturing Practice (GMP) level autologous adipose stem cells (ASCs) with progressively increasing usage of computer-aided manufacturing (CAM) technology.
  
  
  METHODS
  Patients' three-dimensional (3D) images were used in three consecutive patients to plan and reverse-engineer patient-specific saw guides and reconstruction plates using computer-aided additive manufacturing. Adipose tissue was harvested from the anterior abdominal walls of three patients before resection. ASCs were expanded ex vivo over 3 weeks and seeded onto a β-TCP scaffold with rhBMP-2. Constructs were implanted into patient resection defects together with rapid prototyped reconstruction plates.
  
  
  RESULTS
  All three cases used one step in situ bone formation without the need for an ectopic bone formation step or vascularized flaps. In two of the three patients, dental implants were placed 10 and 14 months following reconstruction, allowing harvesting of bone cores from the regenerated mandibular defects. Histological examination and in vitro analysis of cell viability and cell surface markers were performed and prosthodontic rehabilitation was completed.
  
  
  CONCLUSIONS
  Constructs with ASCs, β-TCP scaffolds, and rhBMP-2 can be used to reconstruct a variety of large mandibular defects, together with rapid prototyped reconstruction hardware which supports placement of dental implants.
authors.affiliation: Institute of Biomedical Technology, University of Tampere, Tampere, Finland ; Department of Eye, Ear and Oral Diseases, Tampere University Hospital, Tampere, Finland.
authors.forename: Jan
authors.initials: J
authors.lastname: Wolff
authors.forename: George K
authors.initials: GK
authors.lastname: Sándor
authors.forename: Aimo
authors.initials: A
authors.lastname: Miettinen
authors.forename: Veikko J
authors.initials: VJ
authors.lastname: Tuovinen
authors.forename: Bettina
authors.initials: B
authors.lastname: Mannerström
authors.forename: Mimmi
authors.initials: M
authors.lastname: Patrikoski
authors.forename: Susanna
authors.initials: S
authors.lastname: Miettinen
keywords: Adipose-derived stem cells; beta-tricalcium phosphate; bone morphogenetic protein; computer-aided design