title: Sustained release poly (lactic-co-glycolic acid) microspheres of bone morphogenetic protein 2 plasmid/calcium phosphate to promote in vitro bone formation and in vivo ectopic osteogenesis.
abstract: Bone regeneration often requires continuous stimulation to promote local bone formation. In the present study, calcium phosphate (CaPi) was used to promote transfection of human bone morphogenetic protein 2 (BMP-2) cDNA plasmid, and poly (lactic-co-glycolic acid) (PLGA) was used to prepare microspheres of pBMP-2/CaPi (i.e., PLGA@pBMP-2/CaPi) using W/O/W double emulsion solvent evaporation method. We showed that PLGA@pBMP-2/CaPi microspheres were spherical with smooth surface, and the particle size ranged from 0.5 to 35 μm. Encapsulation efficiency was up to 30~50%. The release of BMP-2 cDNA from microspheres continued more than 30 days and constituted, less than 7.5% of total plasmid amount within the first 24 h. Real-time PCR results showed that co-culturing of PLGA@pBMP-2/CaPi with bone marrow-derived mesenchymal stem cells (BMSCs) increased calcium deposition and gene expressions of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), SP7, and collagen type I (COLL I) in a time-dependent manner. Finally, X-ray analysis demonstrated that in vivo delivery of PLGA@pBMP-2/CaPi microspheres into the tibialis anterior muscles of rats promoted the generation of osteoblasts, bone tissue, and bone structure. The findings suggested that PLGA@pBMP-2/CaPi microspheres can promote ectopic osteogenesis in non-bone tissues, with strong prospects in promoting bone regeneration.
authors.affiliation: Department of Pathology, School of Stomatology, Jilin University Changchun, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Qiao
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University Changchun, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Stomatology, Jilin University Changchun, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pathology, School of Stomatology, Jilin University Changchun, China.
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Stomatology, Jilin University Changchun, China.
authors.forename: Jiyu
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Pathology, School of Stomatology, Jilin University Changchun, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pathology, School of Stomatology, Jilin University Changchun, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Pathology, School of Stomatology, Jilin University Changchun, China.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University Changchun, China.
authors.forename: Bai
authors.initials: B
authors.lastname: Yang
keywords: BMP-2 plasmid; PLGA; calcium phosphate; ectopic osteogenesis; microsphere