Combination of porous hydroxyapatite and cationic liposomes as a vector for BMP-2 gene therapy.
The clinical significance of hydroxyapatite (HAP) as a bone substitute has become apparent in recent years and bone morphogenetic protein (BMP) a substance which induces bone has attracted much attention. In this study, a 1.2 cm diameter bone defects created on rabbit cranium were treated with the BMP-2 gene (cDNA plasmid) introduced with porous HAP after completion of hemostasis and the resultant bone formation was analyzed histopathologically. The amounts of bone formation was compared BMP-2 cDNA plasmids were not combined with cationic liposomes as a vector. Four groups of rabbits were compared. In the HAP group the cranial bone defect was treated with HAP containing 40 microg of liposomes and a dummy gene (PU). The BMP gene HAP group was treated with HAP soaked in liposomes and 10 microg of the BMP-2 gene. In addition, a group was treated with the gene without implanting HAP. Bone formation on the cranial defects was evaluated 3, 6 and 9 weeks after the operation, by X-ray and histopathological examinations. Three weeks after the operation there was vigorous bone formation in the cranial defect in the group which received the BMP-2 gene without HAP, and complete ossification was observed at 9 weeks. In the group which received HAP containing the BMP-2 gene, although new bone formation was evident surrounding the scaffold 3 weeks post-operation, the induced bone tissue did not fill all the pores of the scaffold even at 9 weeks post-operation. These results confirm the clinical usefulness of gene therapy for bone formation, using the BMP-2 gene combined with cationic liposomes as a vector. It is possible that the effects of administering the BMP-2 gene will be improved by specializing the microstructure of scaffold for gene therapy.
Ono
Ichiro
I
Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan. ichiro@sapmed.ac.jp
Yamashita
Toshiharu
T
Jin
Hai-Ying
HY
Ito
Yoshinori
Y
Hamada
Hirobumi
H
Akasaka
Yoshikiyo
Y
Nakasu
Masanori
M
Ogawa
Tetsunori
T
Jimbow
Kowichi
K
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D018786:Bone Substitutes; D002412:Cations; D004337:Drug Carriers / Q000737:chemistry; D004343:Drug Implants / Q000737:chemistry; D017886:Durapatite / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D008081:Liposomes / Q000737:chemistry*; D008422:Materials Testing; D010012:Osteogenesis / Q000187:drug effects; D010957:Plasmids / Q000008:administration & dosage*; D016062:Porosity; D011817:Rabbits; D012887:Skull Fractures / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D014945:Wound Healing / Q000235:genetics
D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018786:Bone Substitutes; D002412:Cations; D004337:Drug Carriers; D004343:Drug Implants; D008081:Liposomes; D016212:Transforming Growth Factor beta; D017886:Durapatite