title: Histological and molecular-biological analyses of poly(3-hydroxybutyrate) (PHB) patches for enhancement of bone regeneration.
abstract: Tissue engineered cell-seeded constructs with poly(3)hydroxybutyrate (PHB) induced ectopic bone formation after implantation into the back muscle of rats. The objective of our in vivo study was to evaluate the osteogenic potential of pure PHB patches in surgically created cranial defects. For this, PHB patches were analyzed after implantation in surgically created defects on the cranium of adult male rats. After healing periods of 4, 8 and 12 weeks, the bone tissue specimens containing PHB patches were processed and analyzed histologically as well as molecular-biologically. After 4 weeks, the PHB patches were completely embedded in connective tissue. Eight weeks after PHB insertion, bone regeneration proceeding from bearing bone was found in 50% of all treated animals, whereas all PHB treated cavities showed both bone formation and embedding of the patches in bone 12 weeks after surgery. Furthermore, all slices showed pronounced development of blood vessels. Histomorphometric analysis presented a regenerated bone mean value between 46.4 ± 16.1% and 54.2 ± 19.3% after 4-12 weeks of healing. Caveolin-1 staining in capillary-like structures showed a 1.16-1.38 fold increased expression in PHB treated defects compared to controls. Real-time RT-PCR analyses showed significantly lower expressions of Alpl, Col1a1 and VEGFA in cranium defects after treatment with PHB patches compared to untreated bony defects of the same cranium. Within the limits of the presented animal investigation, it could conclude that the tested PHB patches featured a good biocompatibility and an osteoconductive character.
authors.affiliation: Department of Orthodontics, Carl Gustav Carus Campus, Technische Universität Dresden, Germany. Electronic address: tomasz.gredes@uniklinikum-dresden.de.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gredes
authors.affiliation: Department of Orthodontics, Carl Gustav Carus Campus, Technische Universität Dresden, Germany.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gedrange
authors.affiliation: Leibniz Institute of Polymer Research Dresden e. V., Dresden, Germany; Institute of Material Science, Technische Universität Dresden, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Hinüber
authors.affiliation: Centre for Translational Bone, Joint and Soft tissue research, Carl Gustav Carus Campus, Technische Universität, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gelinsky
authors.affiliation: Department of Orthodontics, Carl Gustav Carus Campus, Technische Universität Dresden, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Kunert-Keil
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism; D002828:Choristoma / Q000473:pathology; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D003238:Connective Tissue / Q000254:growth & development; D049308:Dioxygenases / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006885:Hydroxybutyrates / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000254:growth & development / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011091:Polyesters / Q000008:administration & dosage / Q000494:pharmacology*; D000091402:Prohibitins; D051381:Rats; D011917:Rats, Inbred Lew; D012886:Skull / Q000187:drug effects / Q000254:growth & development; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D000094122:Polyhydroxybutyrates
chemical_list: D051242:Caveolin 1; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D049308:Dioxygenases; D006885:Hydroxybutyrates; D011091:Polyesters; D000091402:Prohibitins; D042461:Vascular Endothelial Growth Factor A; C000717332:Phb protein, rat; C467498:vascular endothelial growth factor A, rat; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates; C483684:Adi1 protein, rat
keywords: Biocompatibility; Bone healing; Osteoconduction; Rat cranium