title: Sustained dual release of placental growth factor-2 and bone morphogenic protein-2 from heparin-based nanocomplexes for direct osteogenesis.
abstract: OBJECTIVE
  To compare the direct osteogenic effect between placental growth factor-2 (PlGF-2) and bone morphogenic protein-2 (BMP-2).
  
  
  METHODS
  Three groups of PlGF-2/BMP-2-loaded heparin-N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) nanocomplexes were prepared: those with 0.5 μg PlGF-2; with 1.0 μg BMP-2; and with 0.5 μg PlGF-2 combined with 1.0 μg BMP-2. The loading efficiencies and release profiles of these growth factors (GFs) in this nanocomplex system were quantified using enzyme-linked immunosorbent assay, their biological activities were evaluated using cell counting kit-8, cell morphology, and cell number counting assays, and their osteogenic activities were quantified using alkaline phosphatase and Alizarin Red S staining assays.
  
  
  RESULTS
  The loading efficiencies were more than 99% for the nanocomplexes loaded with just PlGF-2 and for those loaded with both PlGF-2 and BMP-2. For the nanocomplex loaded with just BMP-2, the loading efficiency was more than 97%. About 83%-84% of PlGF-2 and 89%-91% of BMP-2 were stably retained on the nanocomplexes for at least 21 days. In in vitro biological assays, PlGF-2 exhibited osteogenic effects comparable to those of BMP-2 despite its dose in the experiments being lower than that of BMP-2. Moreover, the results implied that heparin-based nanocomplexes encapsulating two GFs have enhanced potential in the enhancement of osteoblast function.
  
  
  CONCLUSIONS
  PlGF-2-loaded heparin-HTCC nanocomplexes may constitute a promising system for bone regeneration. Moreover, the dual delivery of PlGF-2 and BMP-2 appears to have greater potential in bone tissue regeneration than the delivery of either GFs alone.
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: PCFM Lab, Sun Yat-sen University, Guangzhou, People's Republic of China; GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Deng
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Hai-Peng
authors.initials: HP
authors.lastname: Sun
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Jia-Yun
authors.initials: JY
authors.lastname: Xu
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.affiliation: PCFM Lab, Sun Yat-sen University, Guangzhou, People's Republic of China; GDHPPC Lab, Institute of Polymer Science, Department of Polymer and Materials Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhang
authors.affiliation: Department of Oral Implantology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, People's Republic of China.
authors.forename: Fei-Long
authors.initials: FL
authors.lastname: Deng
mesh_terms: D016475:3T3 Cells; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000493:pharmacokinetics* / Q000494:pharmacology; D001861:Bone Regeneration; D048271:Chitosan / Q000031:analogs & derivatives / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D006493:Heparin / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D053761:Nanocomposites / Q000737:chemistry*; D010012:Osteogenesis / Q000187:drug effects*; D000072483:Placenta Growth Factor / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D055396:Bone Morphogenetic Protein 2; C118071:N-trimethyl chitosan chloride; C495830:chitosan-N-2-hydroxypropyl trimethyl ammonium chloride; D000072483:Placenta Growth Factor; D006493:Heparin; D048271:Chitosan
keywords: bone morphogenic protein-2; heparin; nanocomplexes; osteogenesis; placental growth factor-2