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Combination of Controlled Release Platelet-Rich Plasma Alginate Beads and Bone Morphogenetic Protein-2 Genetically Modified Mesenchymal Stem Cells for Bone Regeneration.

ABSTRACT: Platelet-rich plasma (PRP) consists of platelet-derived growth factor and transforming growth factor-? 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.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.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.Sustained release of PRP along with BMP2-modified MSCs can significantly promote bone regeneration.

SUBMITTER: Fernandes G

PROVIDER: S-EPMC4927087 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Combination of Controlled Release Platelet-Rich Plasma Alginate Beads and Bone Morphogenetic Protein-2 Genetically Modified Mesenchymal Stem Cells for Bone Regeneration.

Fernandes Gabriela G Wang Changdong C Yuan Xue X Liu Zunpeng Z Dziak Rosemary R Yang Shuying S

Journal of periodontology 20160108 4

<h4>Background</h4>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 eff ...[more]

PMID: 26745613

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Project description:The repair and treatment of lost or damaged alveolar bone is of great significance in dentistry. Gene-activated matrix (GAM) technology provides a new way for bone regeneration. It is a local gene delivery system, which can not only recruit cells, but also influence their fate. For this purpose, we fabricated a bone morphogenetic protein 2 (BMP-2) gene-loaded absorbable gelatin sponge (AGS) and studied its effect on promoting alveolar bone formation and preventing resorption following tooth extraction in rats. In order to obtain better transfection efficiency, polyethylenimine-alginate (PEI-al) nanocomposites were synthesized and used as gene vectors to deliver BMP-2 cDNA plasmids (PEI-al/pBMP-2). The transfection efficiency, BMP-2 protein expression and osteogenic differentiation of the cells were investigated in vitro. In vivo, we established an alveolar bone regeneration model by extracting the rats' left mandibular incisors. The rats were randomly assigned into 3 groups: control group, unfilled sockets; AGS group, sockets filled with PEI-al solution-loaded gelatin sponges; AGS/BMP group, sockets filled with PEI-al/pBMP-2 solution-loaded gelatin sponge. Radiological and histological assays were performed at 4 and 8 weeks later. In vitro transfection assays indicated that PEI-al/pBMP-2 complexes could effectively transfect MC3T3-E1 cells, promoting the secretion of BMP-2 protein for at least 14 days, as well as increasing the expression of osteogenesis-related gene, ALP activity and calcium deposition. In vivo, western blot analysis showed BMP-2 protein was expressed in bone tissues of AGS/BMP group. The relative height of the residual alveolar ridge and bone mineral density (BMD) of the AGS/BMP group were significantly greater than those in the AGS and control groups at 4 and 8 weeks, respectively. Histological examination showed that, at 4 weeks, osteoblasts had grown in a cubic shape around the new bone in the AGS/BMP group, suggesting new bone formation. In conclusion, the combination of PEI-al/pBMP-2 complexes and gelatin sponge could promote alveolar bone regeneration, which may provide an easy and valuable method for alveolar ridge preservation and augmentation.

Dataset Information

Combination of Controlled Release Platelet-Rich Plasma Alginate Beads and Bone Morphogenetic Protein-2 Genetically Modified Mesenchymal Stem Cells for Bone Regeneration.

Publications

Combination of Controlled Release Platelet-Rich Plasma Alginate Beads and Bone Morphogenetic Protein-2 Genetically Modified Mesenchymal Stem Cells for Bone Regeneration.

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