title: Combination of Controlled Release Platelet-Rich Plasma Alginate Beads and Bone Morphogenetic Protein-2 Genetically Modified Mesenchymal Stem Cells for Bone Regeneration.
abstract: BACKGROUND
  Platelet-rich plasma (PRP) consists of platelet-derived growth factor and transforming growth factor-β that increase proliferation of mesenchymal stem cells (MSCs), whereas bone morphogenetic protein-2 (BMP2) promotes osteogenic differentiation of MSCs. However, the high degradation rate of fibrin leads to the dissociation of cytokines even before the process of bone regeneration begins. To the best of the authors' knowledge, this is the first study to examine the combined effect of sustained release of PRP from alginate beads on BMP2-modified MSC osteogenic differentiation in vitro and sustained release of PRP alone on a fracture defect model ex vivo as well as its effect on calvarial suture closure.
  
  
  METHODS
  After optimizing the alginate concentration for microspheres, the combined osteogenic and mineralization effect of PRP and BMP2 on MSCs was studied. Self-setting alginate hydrogel carrying PRP was tested on a femur defect model ex vivo. The effect of PRP at day 15 on the closure of the embryonic mouse calvaria sutures ex vivo was also studied.
  
  
  RESULTS
  Increase of PRP concentration promoted proliferation of MSCs, and 2.5% to 10% of PRP gradually increased alkaline phosphatase (ALP) activity in the cells in a dose-dependent manner. Sustained release of PRP and BMP2 demonstrated significantly higher ALP and mineralization activity (P <0.05). Radiographs of alginate hydrogel with PRP-treated bone demonstrated nearly complete healing of the fracture, and histologic sections of the embryonic calvaria revealed that PRP leads to suture fusion.
  
  
  CONCLUSIONS
  Sustained release of PRP along with BMP2-modified MSCs can significantly promote bone regeneration.
authors.affiliation: Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Fernandes
authors.affiliation: Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY.
authors.forename: Changdong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY.
authors.forename: Xue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY.
authors.forename: Zunpeng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Dziak
authors.affiliation: Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY.|Developmental Genomics Group, New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo.
authors.forename: Shuying
authors.initials: S
authors.lastname: Yang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D001861:Bone Regeneration; D002454:Cell Differentiation; D003692:Delayed-Action Preparations; D059630:Mesenchymal Stem Cells; D051379:Mice; D010012:Osteogenesis; D053657:Platelet-Rich Plasma
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D003692:Delayed-Action Preparations
keywords: Bone regeneration; periodontal regeneration; platelet-rich plasma; stem cells