title: Biological activation of bone-related biomaterials by recombinant adeno-associated virus vector.
abstract: Gene therapy is a promising clinical tool that is no longer limited as a method to supplement genetic deficits, but rather is considered reliable for delivering proteins to specific tissues or cells. Recombinant adeno-associated virus (rAAV) vector is one of the most potent gene transfer vehicles. Many biomaterials have been used in reconstructive surgery, but their biological inactivity has limited their use. To overcome shortcomings of available bone-related biomaterials, we investigated the combination of rAAV with biomaterials. Taking advantage of the method of lyophilizing rAAV onto biomaterials, we showed that an rAAV coating successfully induced beta-galactosidase protein expression by rat fibroblasts on hydroxyapatite, beta-tricalcium phosphate, and titanium alloy in vitro. beta-Galactosidase expression was detected for 8 weeks after implantation of rAAV-coated hydroxyapatite into rat back muscles in vivo. A coating of bone morphogenetic protein-2-expressing rAAV induced significant de novo bone formation on hydroxyapatite in rat back muscles. Our study demonstrates that the combination of lyophilized rAAV and biomaterials presents a promising strategy for bone regenerative medicine.
authors.affiliation: Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Sakyo, Kyoto, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nasu
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tsutsumi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kitaori
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Takemoto
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D001861:Bone Regeneration / Q000502:physiology*; D002130:Calcium Phosphates; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D017886:Durapatite; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005612:Freeze Drying; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014025:Titanium; D014161:Transduction, Genetic / Q000379:methods; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D020099:Coated Materials, Biocompatible; C485817:beta-tricalcium phosphate; D017886:Durapatite; D014025:Titanium; D001616:beta-Galactosidase