title: Biologics and Cell Therapy Tissue Engineering Approaches for the Management of the Edentulous Maxilla: A Systematic Review.
abstract: OBJECTIVE
  The aim of this systematic review was to evaluate current and emerging regenerative approaches for implant site development in the edentulous atrophic maxilla using tissue engineering and regenerative medicine (TERM) principles and to identify priorities for future research.
  
  
  METHODS
  Two independent examiners conducted a comprehensive search using specific keywords to identify original clinical studies using TERM for implant site development in the edentulous atrophic maxilla including indications for alveolar ridge preservation, horizontal alveolar augmentation, maxillary sinus augmentation, and augmentation of severe vertical or combined defects. Endpoints included clinical, radiographic, histologic, and patient-centered outcomes.
  
  
  RESULTS
  The initial search identified 3,061 articles. The final selection included 89 articles, of which 12 evaluated alveolar ridge preservation, 6 horizontal defects, 61 maxillary sinus augmentation, and 11 management of severe vertical or combined defects. A summary of the main findings relative to the effect of TERM-based approaches applied for implant site development in the atrophic maxillary segments is presented. Marked heterogeneity among included studies prevented meaningful quantitative analysis. The following relevant effects of TERM-based therapies for site development in the edentulous atrophic maxilla were observed: (1) recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge carrier increased bone augmentation; (2) recombinant human platelet-derived growth factor BB in combination with freeze-dried bone allograft or beta tricalcium phosphate accelerated bone formation through accelerated remodeling of carrier biomaterials; (3) autologous cell therapy enhanced clinical and radiographic outcomes; (4) autologous cell therapy in alveolar ridge preservation provided superior histomorphometric outcomes (vital bone formation) at 6 weeks; and (5) platelet-rich plasma formulations combined with autologous bone grafts for maxillary sinus augmentation increased radiographic density and accelerated bone mineralization at 6 months.
  
  
  CONCLUSIONS
  Clinical success has been demonstrated with the application of different TERM modalities for implant site development in the edentulous atrophic maxilla. However, indications are narrow and further study is needed. Clinical trials assessing meaningful outcomes, involving larger populations, and with longer follow-up are warranted to discern the effectiveness of the achieved results compared with a valid control.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Avila-Ortiz
authors.forename: P Mark
authors.initials: PM
authors.lastname: Bartold
authors.forename: William
authors.initials: W
authors.lastname: Giannobile
authors.forename: Wataru
authors.initials: W
authors.lastname: Katagiri
authors.forename: Salvador
authors.initials: S
authors.lastname: Nares
authors.forename: Hector
authors.initials: H
authors.lastname: Rios
authors.forename: Daniel
authors.initials: D
authors.lastname: Spagnoli
authors.forename: Ulf Me
authors.initials: UM
authors.lastname: Wikesjö
mesh_terms: D000540:Alveolar Ridge Augmentation / Q000379:methods*; D001688:Biological Products / Q000627:therapeutic use*; D055396:Bone Morphogenetic Protein 2 / Q000627:therapeutic use; D016025:Bone Transplantation / Q000379:methods*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D003758:Dental Implantation, Endosseous / Q000379:methods*; D015921:Dental Implants; D006801:Humans; D008437:Maxilla / Q000473:pathology / Q000601:surgery*; D008443:Maxillary Sinus / Q000601:surgery; D009066:Mouth, Edentulous / Q000601:surgery*; D053657:Platelet-Rich Plasma; D011994:Recombinant Proteins / Q000627:therapeutic use; D023822:Tissue Engineering / Q000379:methods*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use
chemical_list: D001688:Biological Products; D055396:Bone Morphogenetic Protein 2; D015921:Dental Implants; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2