title: PEG matrix enables cell-mediated local BMP-2 gene delivery and increased bone formation in a porcine critical size defect model of craniofacial bone regeneration.
abstract: OBJECTIVE
  This study addressed the suitability of a polyethylene glycol (PEG) matrix as scaffold for cell-mediated local BMP-2 gene transfer in a calvarial critical size defect (CSD) model.
  
  
  METHODS
  PEG matrix (degradation time 10 days) and PEG membrane (degradation time 120 days) were used in the pig calvarial model. Cylindrical (1 × 1 cm) CSD (9 per animal; 20 animals) were filled with: (i) HA/TCP, covered by PEG membrane (group 1); (ii) HA/TCP, mixed with PEG matrix (group 2); and (iii) HA/TCP mixed with BMP-2 transfected osteoblasts and PEG matrix (group 3). BMP-2/4 gene transfer: liposomal in vitro transfection of BMP-2/V5-tag fusion-protein. Quantitative histomorphometry (toluidine blue staining) after 2, 4 and 12 weeks assessed bone formation. Semiquantitative immunohistochemistry estimated the expression of BMP-2 and V5-tag.
  
  
  RESULTS
  Group 3 showed significantly higher new bone formation than groups 1, 2 at 4 (P < 0.05) and 12 (P < 0.02) weeks. BMP-2-V5-tag was detected for 4 weeks. BMP-2 expression in group 3 was higher compared to all other groups after 2 and 4 (P < 0.02) weeks.
  
  
  CONCLUSIONS
  The PEG matrix serves as scaffold for cell-mediated BMP-2 gene delivery in guided bone regeneration facilitating cell survival and protein synthesis for at least 4 weeks. Local BMP-2 gene delivery by PEG matrix-embedded cells leads to increased bone formation during critical size defect regeneration.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Erlangen, Germany. falk.wehrhan@uk-erlangen.de
authors.forename: Falk
authors.initials: F
authors.lastname: Wehrhan
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Aart
authors.initials: A
authors.lastname: Molenberg
authors.forename: Rainer
authors.initials: R
authors.lastname: Lutz
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Neukam
authors.forename: Karl A
authors.initials: KA
authors.lastname: Schlegel
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D018014:Gene Transfer Techniques; D007150:Immunohistochemistry; D008081:Liposomes; D008567:Membranes, Artificial; D011092:Polyethylene Glycols / Q000494:pharmacology*; D012886:Skull / Q000601:surgery*; D013552:Swine; D054457:Tissue Scaffolds; D014048:Tolonium Chloride
chemical_list: D055396:Bone Morphogenetic Protein 2; D008081:Liposomes; D008567:Membranes, Artificial; D014048:Tolonium Chloride; D011092:Polyethylene Glycols