Volume 21, Issue 2 (2018)                   mjms 2018, 21(2): 65-72 | Back to browse issues page

XML Persian Abstract Print

1- Life Science Engineering Department, New Sciences & Technologies Faculty, University of Tehran, Tehran, ‎Iran
2- Chemical Engineering Departmen, Chemical Engineering Faculty, University of Tehran, Tehran, Iran , amoabediny@ut.ac.ir
3- Stem Cells & Developmental Biology Department, Cell Science Research Center, Royan Institute for Stem Cell ‎Biology & Technology, Tehran, Iran
4- Biotechnology Department, Chemical Engineering Faculty, Tarbiat Modares University, Tehran, Iran
5- Oral Cell Biology Department, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam & ‎VU University, Amsterdam, The Netherlands
Abstract:   (8117 Views)
Aims: Growth factor (GFs) delivery with the certain concentration and release kinetic is one of the main challenges in tissue engineering. The aim of this study was the preparation and characterization of smart poly (N-isopropylacrylamide) nanoparticles containing vascular endothelial growth factor for induction of angiogenesis in human bone marrow-derived mesenchymal stem cells.
Materials and Methods: In this exprimental study, two different formulations of temperature-sensitive Poly (N-isopropylacrylamide) (PNIPAM) nanoparticles (NPs) were synthesized by free radical polymerization technique. Nanoprecipitation and diffusion methods were used to load the vascular endothelial growth factor (VEGF) in PNIPAM NPs. The effects of released VEGF on the differentiation of human bone marrow stem cells (hBMSCs) into endothelial cells in angiogenic, osteogenic, and 50% angiogenic-osteogenic culture medium were investigated, using flow cytometry and light microscope. Statistical analysis was performed, using the GraphPad Prism 6 software.
Findings: The nanoprecipitation process caused polymer degradation due to using the organic N, N-Dimethylacetamide solvent. The cumulative VEGF released after 72hours for 70%. A total of 10ng/ml VEGF released from PNIPAM nanoparticles, in 2D culture with cell density of 3×104 hBMSCs, after 7 days, leading to the endothelial differentiation, capillary-like tube formation, and expression of 20% vWF as angiogenic marker.
Conclusion: The PNIPAM NPs have the potential to load and release the angiogenic GFs for induction of angiogenesis in hBMSCs and in osteogenic medium.
Full-Text [PDF 653 kb]   (1469 Downloads)    
Article Type: Original Manuscipt | Subject: Biochemistry
Received: 2017/12/11 | Accepted: 2018/02/26

1. Vo TN, Kasper FK, Mikos AG. Strategies for controlled delivery of growth factors and cells for bone ‎regeneration. Adv Drug Deliv Rev. 2012;64(12):1292-309. ‎ [Link] [DOI:10.1016/j.addr.2012.01.016]
2. Chen FM, Zhang M, Wu ZF. Toward delivery of multiple growth factors in tissue engineering. Biomaterials. ‎‎2010;31(24):6279-308.‎ [Link] [DOI:10.1016/j.biomaterials.2010.04.053]
3. Li P, Xu K, Tan Y, Lu C, Li Y, Wang P. A novel fabrication method of temperature-responsive poly ‎‎(acrylamide) composite hydrogel with high mechanical strength. Polymer. 2013;54(21):5830-8. ‎ [Link] [DOI:10.1016/j.polymer.2013.08.019]
4. Kuckling D, Krahl ADF, Krahl F, Arndt KF. Stimuli-responsive polymer systems. Polym Sci, Compr Ref. ‎‎2012;8:377-413. ‎ [Link]
5. Hoffman AS. Stimuli-responsive polymers: Biomedical applications and challenges for clinical translation. ‎Adv Drug Deliv Rev. 2013;65(1):10-6.‎ [Link] [DOI:10.1016/j.addr.2012.11.004]
6. Hathawaya H, Alves DR, Bean J, Esteban PP, Ouadi K, Sutton JM, et al. Poly(N-isopropylacrylamide-co-‎allylamine) (PNIPAM-co-ALA) nanospheres for the thermally triggered release of Bacteriophage K. Eur J ‎Pharm Biopharm. 2015;96:437-41.‎ [Link]
7. Rejinold NS, Baby T, Chennazhi KP, Jayakumar R. Dual drug encapsulated thermo-sensitive fibrinogen-‎graft-poly (N-isopropyl acrylamide) nanogels for breast cancer therapy. Colloids Surf B Biointerfaces. ‎‎2014;114:209-17.‎ [Link] [DOI:10.1016/j.colsurfb.2013.10.015]
8. Joshi RV, Nelson CE, Poole KM, Skala MC, Duvall CL. Dual pH- and temperature-responsive microparticles ‎for protein delivery to ischemic tissues. Acta Biomater. 2013;9(5):6526-34.‎ [Link] [DOI:10.1016/j.actbio.2013.01.041]
9. Ertan AB, Yılgor P, Bayyurt B, Çalıkoğlu AC, Kaspar Ç, Kök FN, et al. Effect of double growth factor release ‎on cartilage tissue engineering. J Tissue Eng Regen Med. 2013;7(2):149-60. ‎ [Link]
10. ‎Garbern JC, Hoffman AS, Stayton PS. Injectable pH- and temperature-responsive poly (N-‎isopropylacrylamide-co-propylacrylic acid) copolymers for delivery of angiogenic growth factors. ‎Biomacromolecules. 2010;11(7):1833-9.‎ [Link] [DOI:10.1021/bm100318z]
11. Naddaf AA, Tsibranska I, Bart HJ. Kinetics of BSA release from poly (N- isopropylacrylamide) hydrogels, ‎Chem Eng Process, Process Intensif . 2010;49(6):581–8.‎ [Link] [DOI:10.1016/j.cep.2010.05.008]
12. Das S, Suresh PK, Desmukh R. Design of Eudragit RL 100 nanoparticles by nanoprecipitation method for ‎ocular drug delivery. Nanomedicine. 2010;6(2):318-23.‎ [Link]
13. Rao JP, Geckeler KE. Polymer nanoparticles: Preparation techniques and size-control parameters. Prog ‎Polym Sci. 2011;36(7):887-913.‎ [Link]
14. Chim SM, Tickner J, Chow ST, Kuek V, Guo B, Zhang G, et al. Angiogenic factors in bone local environment. ‎Cytokine Growth Factor Rev. 2013;24(3):297-310. ‎ [Link]
15. Odedra D, Chiu LL, Shoichet M, Radisic M. Endothelial cells guided by immobilized gradients of vascular ‎endothelial growth factor on porous collagen scaffolds. Acta Biomater. 2011;7(8):3027-35. ‎ [Link] [DOI:10.1016/j.actbio.2011.05.002]
16. Chen RR, Silva EA, Yuen WW, Brock AA, Fischbach C, Lin AS, et al. Integrated approach to designing ‎growth factor delivery systems. FASEB J. 2007;21(14):3896-903.‎ [Link]
17. Böhrnsen F, Schliephake H. Supportive angiogenic and osteogenic differentiation of mesenchymal stromal ‎cells and endothelial cells in monolayer and co-cultures. Int J Oral Sci. 2016;8(4):223-30. ‎ [Link] [DOI:10.1038/ijos.2016.39]
18. Bronckaers A, Hilkens P, Martens W, Gervois P, Ratajczak J, Struys T, et al. Mesenchymal stem/stromal ‎cells as a pharmacological and therapeutic approach to accelerate angiogenesis. Pharmacol Ther. ‎‎2014;143(2):181-96.‎ [Link]
19. Bai Y, Yin G, Huang Z, Liao X, Chen X, Yao Y, et al. Localized delivery of growth factors for angiogenesis ‎and bone formation in tissue engineering. Int Immunopharmacol. 2013;16(2):214-23. ‎ [Link]
20. Probst A, Spiegel HU. Cellular mechanisms of bone repair. J Invest Surg. 1997;10(3):77-86.‎ [Link] [DOI:10.3109/08941939709032137]
21. Mikos AG, Sarakinos G, Lyman MD, Ingber DE, Vacanti JP, Langer R. Prevascularization of porous ‎biodegradable polymers. Biotechnol Bioeng. 1993;42(6):716-23.‎ [Link]
22. Lokmic Z, Mitchell GM. Engineering the microcirculation. Tissue Eng Part B Rev. 2008;14(1):87-103. ‎ [Link]
23. Kang Y, Kim S, Fahrenholtz M, Khademhosseini A, Yang Y. Osteogenic and angiogenic potentials of ‎monocultured and co-cultured human-bone-marrow-derived mesenchymal stem cells and human-umbilical-‎vein endothelial cells on three-dimensional porous beta-tricalcium phosphate scaffold. Acta Biomater. ‎‎2013;9(1):4906-15. ‎ [Link] [DOI:10.1016/j.actbio.2012.08.008]
24. DeCicco-Skinner KL, Henry GH, Cataisson C, Tabib T, Gwilliam JC, Watson NJ, et al. Endothelial cell tube ‎formation assay for the in vitro study of angiogenesis. J Vis Exp. 2014;(91):e51312.‎ [Link]
25. Bucatariu S, Fundueanu G, Prisacaru I, Balan M, Stoica I, Harabagiu V, et al. Synthesis and ‎characterization of thermosensitive poly (N-isopropylacrylamide-co-hydroxyethylacrylamide) microgels as ‎potential carriers for drug delivery. J Polym Res. 2014;21:580.‎ [Link]
26. Alf ME, Alan Hatton T, Gleason KK. Novel N-isopropylacrylamide based polymer architecture for faster ‎LCST transition kinetics. Polymer. 2011;52(20):4429-34.‎ [Link] [DOI:10.1016/j.polymer.2011.07.051]
27. Reis CP, Neufeld RJ, Ribeiro AJ, Veiga F. Nanoencapsulation I. Methods for preparation of drug-loaded ‎polymeric nanoparticles. Nanomedicine. 2006;2(1):8-21. ‎ [Link]
28. Chen MY, Lie PC, Li ZL, Wei X. Endothelial differentiation of Wharton's jelly-derived mesenchymal stem ‎cells in comparison with bone marrow-derived mesenchymal stem cells. Exp Hematol. 2009;37(5):629-40.‎ [Link] [DOI:10.1016/j.exphem.2009.02.003]
29. Birmingham E, Niebur GL, McHugh PE, Shaw G, Barry FP, McNamara LM. Osteogenic differentiation of ‎mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche. Eur Cell ‎Mater. 2012;23:13-27.‎ [Link]

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.