Abstract
Background
Although progenitor cells have been observed in articular cartilage, this part has a limited ability to repair due to a lack of blood supply. Formerly, tissue engineering was mainly based on collecting chondrocytes from the joint surface, culturing them on resorbable scaffolds such as poly D, L-lactic glycolic acid (PLGA) and then autologous transplantation. In recent times, due to difficulties in collecting chondrocytes, most of the researchers are focused on stem cells for producing these cells. Among the important factors in this approach, is using appropriate scaffolds with good mechanical and biological properties to provide optimal environment for growth and development of stem cells. In this study, we evaluated the potential of fibrin glue, PLGA and alginate scaffolds in providing a suitable environment for growth and chondrogenic differentiation of mesenchymal stem cells (MSCs) in the presence of transforming growth factor-β3.
Materials and Methods
Fibrin glue, PLGA and alginate scaffolds were prepared and MSCs were isolated from human adipose tissue. Cells were cultured separately on the scaffolds and 2 weeks after differentiation, chondrogenic genes, cell proliferation ability and morphology in each scaffold were evaluated using real time-polymerase chain reaction, MTT chondrogenic assay and histological examination, respectively.
Results
Proliferation of differentiated adipose tissue derived mesenchymal stem cells (AD-MSCs) to chondrogenic cells in Fibrin glue were significantly higher than in other scaffolds. Also, Fibrin glue caused the highest expression of chondrogenic genes compared to the other scaffolds. Histological examination revealed that the pores of the Fibrin glue scaffolds were filled with cells uniformly distributed.
Conclusion
According to the results of the study, it can be concluded that natural scaffolds such as fibrin can be used as an appropriate environment for cartilage differentiation.
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Change history
09 September 2022
This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1007/s43465-022-00738-w
References
Khan IM, Gilbert SJ, Singhrao SK, Duance VC, Archer CW. Cartilage integration: Evaluation of the reasons for failure of integration during cartilage repair. A review. Eur Cell Mater 2008;16:26–39.
Yarlagadda PK, Chandrasekharan M, Shyan JY. Recent advances and current developments in tissue scaffolding. Biomed Mater Eng 2005;15:159–77.
Dhandayuthapani B, Yoshida Y, Maekawa T, Kumar DS. Polymeric scaffolds in tissue engineering application: A review. Int J Polym Sci 2011;290602:1–19.
Zhu J, Marchant RE. Design properties of hydrogel tissueengineering scaffolds. Expert Rev Med Devices 2011;8:607–26.
Wagenseil JE, Mecham RP. Vascular extracellular matrix and arterial mechanics. Physiol Rev 2009;89:957–89.
Cao Y, Wang B. Biodegradation of silk biomaterials. Int J Mol Sci 2009;10:1514–24.
Chan BP, Leong KW. Scaffolding in tissue engineering: General approaches and tissue-specific considerations. Eur Spine J 2008;17 Suppl 4:467–79.
Moon JJ, West JL. Vascularization of engineered tissues: Approaches to promote angio-genesis in biomaterials. Curr Top Med Chem 2008;8:300–10.
Sundelacruz S, Kaplan DL. Stem cell- and scaffold-based tissue engineering approaches to osteochondral regenerative medicine. Semin Cell Dev Biol 2009;20:646–55.
McCall JD, Luoma JE, Anseth KS. Covalently tethered transforming growth factor beta in PEG hydrogels promotes chondrogenic differentiation of encapsulated human mesenchymal stem cells. Drug Deliv Transl Res 2012;2:305–12.
Nicodemus GD, Bryant SJ. Cell encapsulation in biodegradable hydrogels for tissue engineering applications. Tissue Eng Part B Rev 2008;14:149–65.
Ma K, Titan AL, Stafford M, Zheng Ch, Levenston ME. Variations in chondrogenesis of human bone marrow-derived mesenchymal stem cells in fibrin/alginate blended hydrogels. Acta Biomater 2012;8:3754–64.
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.
Pilia M, Guda T, Appleford M. Development of composite scaffolds for load-bearing segmental bone defects. Biomed Res Int 2013;2013:458253.
Lü JM, Wang X, Marin-Muller C, Wang H, Lin PH, Yao Q, et al. Current advances in research and clinical applications of PLGA-based nanotechnology. Expert Rev Mol Diagn 2009;9:325–41.
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.
Chen WC, Yao CL, Wei YH, Chu IM. Evaluating osteochondral defect repair potential of autologous rabbit bone marrow cells on type II collagen scaffold. Cytotechnology 2011;63:13–23.
Awad HA, Wickham MQ, Leddy HA, Gimble JM, Guilak F. Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 2004;25:3211–22.
Sun J, Tan H. Alginate-based biomaterials for regenerative medicine applications. Materials 2013;6:1285–309.
Wang W, Li B, Yang J, Xin L, Li Y, Yin H, et al. The restoration of full-thickness cartilage defects with BMSCs and TGFbeta 1 loaded PLGA/fibrin gel constructs. Biomaterials 2010;31:8964–73.
Danišovic L, Varga I, Polák S. Growth factors and chondrogenic differentiation of mesenchymal stem cells. Tissue Cell 2012;44:69–73.
http://www.ebi.ac.uk. Hinxton: The European Bioinformatics Institute, European Molecular Biology Laboratory (EMBL); c1992-2014. Available from: http://www.ebi.ac.uk/interpro/entry/IPR015618. [Last updated on 2013 Nov 27; Last cited on 2014 Jan 27].
Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 2007;327:449–62.
Ajibade DA, Vance DD, Hare JM, Kaplan LD, Lesniak BP. Emerging applications of stem cell and regenerative medicine to sports injuries. Orthop J Sports Med 2014;2:17.
Brown PT, Handorf AM, Jeon WB, Li WJ. Stem cell-based tissue engineering approaches for musculoskeletal regeneration. Curr Pharm Des 2013;19:3429–45.
Tuan RS, Boland G, Tuli R. Adult mesenchymal stem cells and cell-based tissue engineering. Arthritis Res Ther 2003;5:32–45.
Chen FH, Rousche KT, Tuan RS. Technology insight: Adult stem cells in cartilage regeneration and tissue engineering. Nat Clin Pract Rheumatol 2006;2:373–82.
Chen FH, Tuan RS. Mesenchymal stem cells in arthritic diseases. Arthritis Res Ther 2008;10:223.
Kessler MW, Grande DA. Tissue engineering and cartilage. Organogenesis 2008;4:1, 28–32.
Diekman BO, Guilak F. Stem cell-based therapies for osteoarthritis: Challenges and opportunities. Curr Opin Rheumatol 2013;25:119–26.
Drobnic M, Kregar-Velikonja N, Radosavljevic D, Gorensek M, Koritnik B, Malicev E, et al. The outcome of autologous chondrocyte transplantation treatment of cartilage lesions in the knee. Cell Mol Biol Lett 2002;7:361–3.
Fan H, Hu Y, Zhang C, Li X, Lv R, Qin L, et al. Cartilage regeneration using mesenchymal stem cells and a PLGAgelatin/chondroitin/hyaluronate hybrid scaffold. Biomaterials 2006;27:4573–80.
Frenkel SR, Bradica G, Brekke JH, Goldman SM, Ieska K, Issack P, et al. Regeneration of articular cartilage–evaluation of osteochondral defect repair in the rabbit using multiphasic implants. Osteoarthritis Cartilage 2005;13:798–807.
Johnstone B, Alini M, Cucchiarini M, Dodge GR, Eglin D, Guilak F, et al. Tissue engineering for articular cartilage repair–the state of the art. Eur Cell Mater 2013;25:248–67.
Mainil-Varlet P. A validated histological score for human cartilage biopsies in clinical trial. Presentation, 7th World Congress of the International Cartilage Repair Society, Warzaw, Poland; 2007.
Matsiko A, Levingstone TJ, O’Brien FJ. Advanced strategies for articular cartilage defect repair. Materials 2013;6:637–68.
McCarty R, Leavesley DI, Simmons P. Application of mesenchymal stem cells for repair and regeneration of cartilage and bone. Aust Biochem 2005;36:7–10.
O’Driscoll SW, Keeley FW, Salter RB. Durability of regenerated articular cartilage produced by free autogenous periosteal grafts in major full-thickness defects in joint surfaces under the influence of continuous passive motion. A followup report at one year. J Bone Joint Surg Am 1988;70:595–606.
Parchi PD, Vittorio O, Andreani L, Piolanti N, Andreani L, Poggetti A, Lisanti M. How nanotechnology can really improve the future of orthopedic implants and scaffolds for bone and cartilage defects. J Nanomedine Biotherapeutic Discov 2013;3:114.
Qi Y, Zhao T, Xu K, Dai T, Yan W. The restoration of fullthickness cartilage defects with mesenchymal stem cells (MSCs) loaded and cross-linked bilayer collagen scaffolds on rabbit model. Mol Biol Rep 2012;39:1231–7.
Roelofs AJ, Rocke JP, De Bari C. Cell-based approaches to joint surface repair: A research perspective. Osteoarthritis Cartilage 2013;21:892–900.
Shapiro F, Koide S, Glimcher MJ. Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. J Bone Joint Surg Am 1993;75:532–53.
Wakitani S, Yamamoto T. Response of the donor and recipient cells in mesenchymal cell transplantation to cartilage defect. Microsc Res Tech 2002;58:14–8.
Yang P, Huang X, Wang C, Dang X, Wang K. Repair of bone defects using a new biomimetic construction fabricated by adipose-derived stem cells, collagen I, and porous betatricalcium phosphate scaffolds. Exp Biol Med (Maywood) 2013;238:1331–43.
Zhang L, Hu J, Athanasiou KA. The role of tissue engineering in articular cartilage repair and regeneration. Crit Rev Biomed Eng 2009;37:1–57.
Guilak F, Awad HA, Fermor B, Leddy HA, Gimble JM. Adiposederived adult stem cells for cartilage tissue engineering. Biorheology 2004;41:389–99.
Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006;24:1294–301.
Shahdadfar A, Frønsdal K, Haug T, Reinholt FP, Brinchmann JE. In vitro expansion of human mesenchymal stem cells: Choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. Stem Cells 2005;23:1357–66.
Veronesi F, Maglio M, Tschon M, Aldini NN, Fini M. Adipose-derived mesenchymal stem cells for cartilage tissue engineering: State-of-the-art in in vivo studies. J Biomed Mater Res A 2014;102:2448–66.
Zhu Y, Liu T, Song K, Fan X, Ma X, Cui Z. Adipose-derived stem cell: A better stem cell than BMSC. Cell Biochem Funct 2008;26:664–75.
Mardani M, Hashemibeni B, Ansar MM, Zarkesh Esfahani SH, Kazemi M, Goharian V, et al. Comparison between chondrogenic markers of differentiated chondrocytes from adipose derived stem cells and articular chondrocytes in vitro. Iran J Basic Med Sci 2013;16:763–73.
Cucchiarini M, Venkatesan JK, Ekici M, Schmitt G, Madry H. Human mesenchymal stem cells overexpressing therapeutic genes: From basic science to clinical applications for articular cartilage repair. Biomed Mater Eng 2012;22:197–208.
Portocarrero G, Collins G, Arinzeh TL. Challenges in cartilage tissue engineering. J Tissue Sci Eng 2013;4:1–2.
Vinatier C, Bouffi C, Merceron C, Gordeladze J, Brondello JM, Jorgensen C, et al. Cartilage tissue engineering: Towards a biomaterial-assisted mesenchymal stem cell therapy. Curr Stem Cell Res Ther 2009;4:318–29.
Iwasa J, Engebretsen L, Shima Y, Ochi M. Clinical application of scaffolds for cartilage tissue engineering. Knee Surg Sports Traumatol Arthrosc 2009;17:561–77.
Koga H, Muneta T, Nagase T, Nimura A, Ju YJ, Mochizuki T, et al. Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: Suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res 2008;333:207–15.
Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, et al. Articular cartilage engineering with hyalograft C: 3-year clinical results. Clin Orthop Relat Res 2005;435:96–105.
Panseri S, Russo A, Cunha C, Bondi A, Di Martino A, Patella S, et al. Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration. Knee Surg Sports Traumatol Arthrosc 2012;20:1182–91.
Im GI, Jung NH, Tae SK. Chondrogenic differentiation of mesenchymal stem cells isolated from patients in late adulthood: The optimal conditions of growth factors. Tissue Eng 2006;12:527–36.
Zwingmann J, Mehlhorn AT, Südkamp N, Stark B, Dauner M, Schmal H. Chondrogenic differentiation of human articular chondrocytes differs in biodegradable PGA/PLA scaffolds. Tissue Eng 2007;13:2335–43.
Zhu J. Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 2010;31:4639–56.
Van Vlierberghe S, Dubruel P, Schacht E. Biopolymer-based hydrogels as scaffolds for tissue engineering applications: A review. Biomacromolecules. 2011;12:1387–408.
Chung C, Erickson IE, Mauck RL, Burdick JA. Differential behavior of auricular and articular chondrocytes in hyaluronic acid hydrogels. Tissue Eng Part A 2008;14:1121–31.
Kreuz PC, Müller S, Ossendorf C, Kaps C, Erggelet C. Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: Four-year clinical results. Arthritis Res Ther 2009;11:R33.
Lindahl A, Brittberg M, Peterson L. Cartilage repair with chondrocytes: Clinical and cellular aspects. Novartis Found Symp 2003;249:175–86.
Laurienzo P. Marine polysaccharides in pharmaceutical applications: An overview. Mar Drugs 2010;8:2435–65.
Spiller KL, Maher SA, Lowman AM. Hydrogels for the repair of articular cartilage defects. Tissue Eng Part B Rev 2011;17:281–99.
Pei M, He F, Kish VL, Vunjak-Novakovic G. Engineering of functional cartilage tissue using stem cells from synovial lining: A preliminary study. Clin Orthop Relat Res 2008;466:1880–9.
Lam G. Exploring the role of hypoxia related parameters in the vascularization of modular tissues. MASc Thesis. Ontario: University of Toronto; 2013.
Cheng NC, Estes BT, Young TH, Guilak F. Engineered cartilage using primary chondrocytes cultured in a porous cartilagederived matrix. Regen Med 2011;6:81–93.
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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1007/s43465-022-00738-w
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Sheykhhasan, M., Qomi, R.T., Kalhor, N. et al. RETRACTED ARTICLE: Evaluation of the ability of natural and synthetic scaffolds in providing an appropriate environment for growth and chondrogenic differentiation of adipose-derived mesenchymal stem cells. IJOO 49, 561–568 (2015). https://doi.org/10.4103/0019-5413.164043
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DOI: https://doi.org/10.4103/0019-5413.164043
Key words
- Adipose-derived mesenchymal stem cells
- alginate
- fibrin glue
- poly D
- L-lactic glycolic acid
- tissue engineering