The effects of fibrin–icariin nanoparticle loaded in poly (lactic-co-glycolic) acid scaffold as a localized delivery system on chondrogenesis of human adipose-derived stem cells

Gorji, Mona; Ghasemi, Nazem; Setayeshmehr, Mohsen; Zargar, Anooshe; Kazemi, Mohammad; Soleimani, Mitra; Hashemibeni, Batool

The effects of fibrin–icariin nanoparticle loaded in poly (lactic-co-glycolic) acid scaffold as a localized delivery system on chondrogenesis of human adipose-derived stem cells

Document Type : Original Article

Authors

¹ Department of Anatomical Sciences and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

² Department of Advanced Medical Technology, Biomaterials Nanaotechnology and Tissue Engineering Group, Isfahan University of Medical Sciences, Isfahan, Iran

³ Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Nowadays, cartilage tissue engineering is the best candidate for regeneration of cartilage defects. This study evaluates the effect of fibrin/icariin (ICA) nanoparticles (F/I NPs) on chondrogenesis of stem cells. Materials and Methods: F/I NPs were characterized by Dynamic Light Scattering DLS. Poly (lactic-co-glycolic) acid (PLGA)-F/I NP scaffold was fabricated and assessed by scanning electron microscope. Human adipose-derived stem cells (hADSCs) were seeded on scaffold and induced for chondrogenesis. After 14 days, cell viability and gene expression were analyzed by the 3-(4, 5- dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. MTT assay and real-time polymerase chain reaction (RT-PCR). Results: The size and surface charge of F/I NP were about 28–30 nm and − 17, respectively. The average of pore size of PLGA and PLGA–fibrin/ICA was 230 and 340 μm, respectively. Cell viability of differentiated cells in P/F group was higher than others significantly (P ≤ 0.05). Furthermore, quantitative RT-PCR analysis demonstrated that ICA upregulated cartilaginous-specific gene expression. Furthermore, the results of the expression of type I collagen revealed that ICA downregulated this gene significantly (P < 0.01). Conclusions: The results indicated that F/I NP could be a potential factor for chondrogenesis of stem cells and downregulation of fibrocartilage marker.

Keywords

References

1.	O'brien FJ. Biomaterials and scaffolds for tissue engineering. Mater Today 2011;14:88-95.
2.	Woo KM, Chen VJ, MaPX. Nano-fibrous scaffolding architecture selectively enhances protein adsorption contributing to cell attachment. J Biomed Mater Res A 2003;67:531-7.
3.	Tavakoli E, Mehdikhani-Nahrkhalaji M, Hashemi-Beni B, Zargar-Kharazi A, Kharaziha M. Preparation, characterization and mechanical assessment of poly (lactide-co-glycolide) hyaluronic acid/fibrin/bioactive glass nano-composite scaffolds for cartilage tissue engineering applications. Procedia Mater Sci 2015;11:124-30.
4.	Mehdikhani-Nahrkhalaji M, Fathi MH, Mortazavi V, Mousavi SB, Hashemi-Beni B, Razavi SM. Novel nanocomposite coating for dental implant applications in vitro and in vivo evaluation. J Mater Sci Mater Med 2012;23:485-95.
5.	Kang SW, Seo SW, Choi CY, Kim BS. Porous poly (lactic-co-glycolic acid) microsphere as cell culture substrate and cell transplantation vehicle for adipose tissue engineering. Tissue Eng Part C Methods 2008;14:25-34.
6.	Song JE, Lee Y, Lee YM, Cho SA, Jang JE, Lee D, et al. Effects of PLGA/Fibrin Scaffolds on Attachment and Proliferation of Costal Cartilage Cells. Polymer Korea. 2013;37:141-7.
7.	Jockenhoevel S, Zund G, Hoerstrup SP, Chalabi K, Sachweh JS, Demircan L, et al. Fibrin gel – Advantages of a new scaffold in cardiovascular tissue engineering. Eur J Cardiothorac Surg 2001;19:424-30.
8.	Munirah S, Kim SH, Ruszymah BH, Khang G. The use of fibrin and poly (lactic-co-glycolic acid) hybrid scaffold for articular cartilage tissue engineering: An in vivo analysis. Eur Cell Mater 2008;15:41-52.
9.	Jung Y, Chung YI, Kim SH, Tae G, Kim YH, Rhie JW, et al. In situ chondrogenic differentiation of human adipose tissue-derived stem cells in a TGF-beta1 loaded fibrin-poly (lactide-caprolactone) nanoparticulate complex. Biomaterials 2009;30:4657-64.
10.	Longobardi L, O'Rear L, Aakula S, Johnstone B, Shimer K, Chytil A, et al. Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF-beta signaling. J Bone Miner Res 2006;21:626-36.
11.	Tuli R, Tuli S, Nandi S, Huang X, Manner PA, Hozack WJ, et al. Transforming growth factor-beta-mediated chondrogenesis of human mesenchymal progenitor cells involves N-cadherin and mitogen-activated protein kinase and Wnt signaling cross-talk. J Biol Chem 2003;278:41227-36.
12.	Nakamura K, Shirai T, Morishita S, Uchida S, Saeki-Miura K, Makishima F. P38 mitogen-activated protein kinase functionally contributes to chondrogenesis induced by growth/differentiation factor-5 in ATDC5 cells. Exp Cell Res 1999;250:351-63.
13.	van Beuningen HM, Glansbeek HL, van der Kraan PM, van den Berg WB. Differential effects of local application of BMP-2 or TGF-beta 1 on both articular cartilage composition and osteophyte formation. Osteoarthritis Cartilage 1998;6:306-17.
14.	Li D, Yuan T, Zhang X, Xiao Y, Wang R, Fan Y. Icariin: A potential promoting compound for cartilage tissue engineering. Osteoarthritis Cartilage 2012;20:1647-56.
15.	Zhang L, Zhang X, Li KF, Li DX, Xiao YM, Fan YJ, et al. Icariin promotes extracellular matrix synthesis and gene expression of chondrocytes in vitro. Phytother Res 2012;26:1385-92.
16.	Sun P, Liu Y, Deng X, Yu C, Dai N, Yuan X, et al. An inhibitor of cathepsin K, icariin suppresses cartilage and bone degradation in mice of collagen-induced arthritis. Phytomedicine 2013;20:975-9.
17.	Wu J, Du J, Xu C, Le J, Liu B, Xu Y, et al. In vivo and in vitro anti-inflammatory effects of a novel derivative of icariin. Immunopharmacol Immunotoxicol 2011;33:49-54.
18.	Jiang W, Kim BY, Rutka JT, Chan WC. Advances and challenges of nanotechnology-based drug delivery systems. Expert Opin Drug Deliv 2007;4:621-33.
19.	Tautzenberger A, Kovtun A, Ignatius A. Nanoparticles and their potential for application in bone. Int J Nanomedicine 2012;7:4545-57.
20.	Kwon IK, Kidoaki S, Matsuda T. Electrospun nano- to microfiber fabrics made of biodegradable copolyesters: Structural characteristics, mechanical properties and cell adhesion potential. Biomaterials 2005;26:3929-39.
21.	Pham QP, Sharma U, Mikos AG. Electrospinning of polymeric nanofibers for tissue engineering applications: A review. Tissue Eng 2006;12:1197-211.
22.	Hashemibeni B, Razavi S, Esfandiary E, Karbasi S, Mardani M, Nasresfahani M. Induction of chondrogenic differentiation of human adipose-derived stem cells with TGF-β3 in pellet culture system. Iran J Basic Med Sci 2008;11:10-7.
23.	Poirot-Mazères I. Legal aspects of the risks raised by nanotechnologies in the field of medicine. J Int Bioethique 2011;22:99-118, 212.
24.	Galvin P, Thompson D, Ryan KB, McCarthy A, Moore AC, Burke CS, et al. Nanoparticle-based drug delivery: Case studies for cancer and cardiovascular applications. Cell Mol Life Sci 2012;69:389-404.
25.	Sajja HK, East MP, Mao H, Wang YA, Nie S, Yang L. Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect. Curr Drug Discov Technol 2009;6:43-51.
26.	Duncan R. The dawning era of polymer therapeutics. Nat Rev Drug Discov 2003;2:347-60.
27.	Praveen G, Sreerekha PR, Menon D, Nair SV, Chennazhi KP. Fibrin nanoconstructs: A novel processing method and their use as controlled delivery agents. Nanotechnology 2012;23:095102.
28.	Rajangam T, An SS. Fibrinogen and fibrin based micro and nano scaffolds incorporated with drugs, proteins, cells and genes for therapeutic biomedical applications. Int J Nanomedicine 2013;8:3641-62.
29.	Vedakumari WS, Prabu P, Babu SC, Sastry TP. Fibrin nanoparticles as possible vehicles for drug delivery. Biochim Biophys Acta 2013;1830:4244-53.
30.	Uematsu K, Hattori K, Ishimoto Y, Yamauchi J, Habata T, Takakura Y, et al. Cartilage regeneration using mesenchymal stem cells and a three-dimensional poly-lactic-glycolic acid (PLGA) scaffold. Biomaterials 2005;26:4273-9.
31.	Croll TI, O'Connor AJ, Stevens GW, Cooper-White JJ. Controllable surface modification of poly (lactic-co-glycolic acid) (PLGA) by hydrolysis or aminolysis I: Physical, chemical, and theoretical aspects. Biomacromolecules 2004;5:463-73.
32.	Sha'ban M, Kim SH, Idrus RB, Khang G. Fibrin and poly (lactic-co-glycolic acid) hybrid scaffold promotes early chondrogenesis of articular chondrocytes: An in vitro study. J Orthop Surg Res 2008;3:17.
33.	Wu SC, Chang JK, Wang CK, Wang GJ, Ho ML. Enhancement of chondrogenesis of human adipose derived stem cells in a hyaluronan-enriched microenvironment. Biomaterials 2010;31:631-40.
34.	Bahrami M, Valiani A, Amirpour N, Ra Rani MZ, Hashemibeni B. Cartilage tissue engineering via icariin and adipose-derived stem cells in fibrin scaffold. Adv Biomed Res 2018;7:36.
35.	Lien SM, Ko LY, Huang TJ. Effect of pore size on ECM secretion and cell growth in gelatin scaffold for articular cartilage tissue engineering. Acta Biomater 2009;5:670-9.
36.	Grad S, Zhou L, Gogolewski S, Alini M. Chondrocytes seeded onto poly (L/DL-lactide) 80%/20% porous scaffolds: A biochemical evaluation. J Biomed Mater Res A 2003;66:571-9.
37.	Lefebvre V, Peeters-Joris C, Vaes G. Production of collagens, collagenase and collagenase inhibitor during the dedifferentiation of articular chondrocytes by serial subcultures. Biochim Biophys Acta 1990;1051:266-75.
38.	Widmer MS, Mikos AG. Fabrication of biodegradable polymer scaffolds for tissue engineering. In: Frontiers in Tissue Engineering. FTE: Elsevier; 1998. p. 107-20.
39.	Wang W, Li B, Yang J, Xin L, Li Y, Yin H, et al. The restoration of full-thickness cartilage defects with BMSCs and TGF-beta 1 loaded PLGA/fibrin gel constructs. Biomaterials 2010;31:8964-73.
40.	Kolambkar YM, Peister A, Soker S, Atala A, Guldberg RE. Chondrogenic differentiation of amniotic fluid-derived stem cells. J Mol Histol 2007;38:405-13.
41.	Jung MR, Shim IK, Chung HJ, Lee HR, Park YJ, Lee MC, et al. Local BMP-7 release from a PLGA scaffolding-matrix for the repair of osteochondral defects in rabbits. J Control Release 2012;162:485-91.
42.	Levi B, James AW, Wan DC, Glotzbach JP, Commons GW, Longaker MT. Regulation of human adipose-derived stromal cell osteogenic differentiation by insulin-like growth factor-1 and platelet-derived growth factor-alpha. Plast Reconstr Surg 2010;126:41-52.
43.	Werle M, Bernkop-Schnürch A. Strategies to improve plasma half life time of peptide and protein drugs. Amino Acids 2006;30:351-67.
44.	Lee RJ, Springer ML, Blanco-Bose WE, Shaw R, Ursell PC, Blau HM. VEGF gene delivery to myocardium: Deleterious effects of unregulated expression. Circulation 2000;102:898-901.
45.	Goya G, Grazu V, Ibarra M. Magnetic nanoparticles for cancer therapy. Curr Nanosci 2008;4:1-16.
46.	Tew SR, Li Y, Pothacharoen P, Tweats LM, Hawkins RE, Hardingham TE. Retroviral transduction with SOX9 enhances re-expression of the chondrocyte phenotype in passaged osteoarthritic human articular chondrocytes. Osteoarthritis Cartilage 2005;13:80-9.
47.	Hsieh TP, Sheu SY, Sun JS, Chen MH, Liu MH. Icariin isolated from Epimedium pubescens regulates osteoblasts anabolism through BMP-2, SMAD4, and cbfa1 expression. Phytomedicine 2010;17:414-23.
48.	Liang W, Lin M, Li X, Li C, Gao B, Gan H, et al. Icariin promotes bone formation via the BMP-2/Smad4 signal transduction pathway in the hFOB 1.19 human osteoblastic cell line. Int J Mol Med 2012;30:889-95.
49.	Liu MH, Sun JS, Tsai SW, Sheu SY, Chen MH. Icariin protects murine chondrocytes from lipopolysaccharide-induced inflammatory responses and extracellular matrix degradation. Nutr Res 2010;30:57-65.
50.	Hashemibeni B, Pourentezari M, Valiani A, Zamani M, Mardani M. Effect of icariin on the chondrogenesis of human adipose derived stem cells on poly (lactic-co-glycolic) acid/fibrin composite scaffold. Int J Adv Biotechnol Res 2017;8:595-605.

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