title: PDGF-B gene therapy accelerates bone engineering and oral implant osseointegration.
abstract: Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due, in part, to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5 x 10(8) or 5.5 x 10(9) pfu ml(-1)), Ad encoding luciferase (Ad-Luc; 5.5 x 10(9) pfu ml(-1); control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg ml(-1)). Bone repair and osseointegration were measured through backscattered scanning electron microscopy, histomorphometry, micro-computed tomography and biomechanical assessments. Furthermore, a panel of local and systemic safety assessments was performed. Results indicated that bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared with Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B shows regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable with rhPDGF-BB protein delivery in vivo.
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: P-C
authors.initials: PC
authors.lastname: Chang
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Seol
authors.forename: J A
authors.initials: JA
authors.lastname: Cirelli
authors.forename: G
authors.initials: G
authors.lastname: Pellegrini
authors.forename: Q
authors.initials: Q
authors.lastname: Jin
authors.forename: L M
authors.initials: LM
authors.lastname: Franco
authors.forename: S A
authors.initials: SA
authors.lastname: Goldstein
authors.forename: L A
authors.initials: LA
authors.lastname: Chandler
authors.forename: B
authors.initials: B
authors.lastname: Sosnowski
authors.forename: W V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D016301:Alveolar Bone Loss / Q000628:therapy*; D000818:Animals; D000077214:Becaplermin; D001861:Bone Regeneration; D003758:Dental Implantation, Endosseous; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D016348:Osseointegration; D017622:Periodontal Attachment Loss; D010982:Platelet-Derived Growth Factor / Q000235:genetics*; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D023822:Tissue Engineering
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D000077214:Becaplermin