Abstract
The aim of this study is to prove the feasibility of a system able to apply local mechanical loading on cells seeded in a hydrogel for tissue engineering applications. This experimental study is based on a previously developed artificial cartilage model with different concentrations of poly(vinyl alcohol) (PVA) that simulates the cartilage extracellular matrix (ECM). Poly(l-lactic acid) (PLLA) microspheres with dispersed magnetic nanoparticles (MNPs) were produced with an emulsion method. These microspheres were embedded in aqueous PVA solutions with varying concentration to resemble increased viscosity of growing tissue during regeneration. The ability to induce a local deformation in the ECM was assessed by applying a steady or an oscillatory magnetic field gradient to different PVA solutions containing the magnetic microparticles, similarly as in ferrogels. PLLA microparticle motion was recorded, and the images were analyzed. Besides, PVA gels and PLLA microparticles were introduced into the pores of a polycaprolactone scaffold, and the microparticle distribution and the mechanical properties of the construct were evaluated. The results of this experimental model show that the dispersion of PLLA microparticles containing MNPs, together with cells in a supporting gel, will allow applying local mechanical stimuli to cells during tissue regeneration. This local stimulation can have a positive effect on the differentiation of seeded cells and improve tissue regeneration.
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References
Eyre D (2002) Collagen of articular cartilage. Arthritis Res 4:30–35
Roughley PJ, Lee ER (1994) Cartilage proteoglycans: structure and potential functions. Microsc Res Tech 28:385–397
Gillard GC, Reilly HC, Bell-Booth PG, Flint MH (1979) The influence of mechanical forces on the glycosaminoglycan content of the rabbit flexor digitorum profundus tendon. Connect Tissue Res 7:37–46
Quinn TM, Grodzinsky AJ, Buschmann MD, Kim YJ, Hunziker EB (1998) Mechanical compression alters proteoglycan deposition and matrix deformation around individual cells in cartilage explants. J Cell Sci 111:573–583
Banes AJ, Tsuzaki M, Yamamoto J, Fischer T, Brigman B, Brown T, Miller L (1995) Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem Cell Biol 73:349–365
Appelman T, Mizrahi J, Elisseeff J, Seliktar D (2011) The influence of biological motifs and dynamic mechanical stimulation in hydrogel scaffold systems on the phenotype of chondrocytes. Biomaterials 32:1508–1516
Mow VC, Ratcliffe A, Poole AR (1992) Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. Biomaterials 13:67–97
Mow VC, Huiskes R (2005) Basic orthopaedic biomechanics and mechano-biology. Lippincott Williams and Wilkins, Philadelphia
Brady MA, Waldman SD, Ethier CR (2015) The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response. Tissue Eng Part B Rev 21:1–19
Valhmu WB, Stazzone EJ, Bachrach NM, Saed-Nejad F, Fischer SG, Mow VC, Ratcliffe A (1998) Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch Biochem Biophys 353:29–36
Ingber DE (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Ann Rev Physiol 59:575–599
Khan S, Sheetz MP (1997) Force effects on biochemical kinetics. Ann Rev Biochem 66:785–805
Hutmacher DW (2000) Scaffolds in tissue engineering bone and cartilage. Biomaterials 21:2529–2543
Crick FHC, Hughes AFW (1950) The physical properties of cytoplasm: a study by means of the magnetic particle method. Exp Cell Res 1:37–80
Valberg PA, Albertini DF (1985) Cytoplasmic motions, rheology, and structure probed by a novel magnetic particle method. J Cell Biol 101:130–140
Valberg PA, Feldman HA (1987) Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity. Biophys J 52:551–561
Wang N, Ingber DE (1995) Probing transmembrane mechanical coupling and cytomechanics using magnetic twisting cytometry. Biochem Cell Biol 73:327–335
Pommerenke H, Schreiber E, Durr F, Nebe B, Hahnel C, Moller W, Rychly J (1996) Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response. Eur J Cell Biol 70:157–164
Bausch AR, Hellerer U, Essler M, Aepfelbacher M, Sackmann E (2001) Rapid stiffening of integrin receptor-actin linkages in endothelial cells stimulated with thrombin: a magnetic bead microrheology study. Biophys J 80:2649–2657
Li L, Yang G, Li J, Ding S, Zhou S (2014) Cell behaviors on magnetic electrospun poly-d, l-lactide nano fibers. Mater Sci Eng, C 34:252–261
Fuhrer R, Hofmann S, Hild N, Vetsch JR, Herrmann IK, Grass RN, Stark WJ (2013) Pressureless mechanical induction of stem cell differentiation is dose and frequency dependent. PLoS One 8:e81362
Cezar CA, Roche ET, Vandenburgh HH, Duda GN, Walsh CJ, Mooney DJ (2016) Biologic-free mechanically induced muscle regeneration. Proc Natl Acad Sci USA 113:1534–1539
Vikingsson L, Gallego Ferrer G, Gómez-Tejedor JA, Gómez Ribelles JL (2014) An in vitro experimental model to predict the mechanical behaviour of macroporous scaffolds implanted in articular cartilage. J Mech Behav Biomed Mater 32:125–131
Vikingsson L, Gomez-Tejedor JA, Gallego Ferrer G, Gomez Ribelles JL (2015) An experimental fatigue study of a porous scaffold for the regeneration of articular cartilage. J Biomech 48:1310–1317
Vikingsson L, Claessens B, Gómez-Tejedor JA, Gallego Ferrer G, Gómez Ribelles JL (2015) Relationship between micro-porosity, water permeability and mechanical behavior in scaffolds for cartilage engineering. J Mech Behav Biomed Mater 48:60–69
Li F, Su YL, Shi DF, Wang CT (2010) Comparison of human articular cartilage and polyvinyl alcohol hydrogel as artificial cartilage in microstructure analysis and unconfined compression. Adv Mater Res Trans Tech Publ 87:188–193
Grant C, Twigg P, Egan A, Moody A, Eagland D, Crowther N, Britland S (2006) Poly(vinyl alcohol) hydrogel as a biocompatible viscoelastic mimetic for articular cartilage. Biotechnol Prog 22:1400–1406
Weeber R, Kantorovich S, Holm C (2015) Ferrogels cross-linked by magnetic nanoparticles—Deformation mechanisms in two and three dimensions studied by means of computer simulations. J Magn Magn Mater 383:262–266
Lebourg M, Suay Antón J, Gómez Ribelles JL (2008) Porous membranes of PLLA–PCL blend for tissue engineering applications. Eur Polym J 44:2207–2218
Santamaría VA, Deplaine H, Mariggió D, Villanueva-Molines AR, García-Aznar JM, Gómez Ribelles JL, Doblaré M, Gallego Ferrer G, Ochoa I (2012) Influence of the macro and micro-porous structure on the mechanical behavior of poly (l-lactic acid) scaffolds. J Non Cryst Solids 358:3141–3149
Panadero JA, Vikingsson L, Gomez Ribelles JL, Lanceros-Mendez S, Sencadas V (2015) In vitro mechanical fatigue behaviour of poly-ε-caprolactone macroporous scaffolds for cartilage tissue engineering. Influence of pore filling by a poly(vinyl alcohol) gel. J Biomed Mater Res Part B Appl Biomater 103:1037–1043
Hassan CM, Peppas NA (2000) Structure and applications of poly(vinyl alcohol) hydrogels produced by conventional crosslinking or by freezing/thawing methods. Adv Polym Sci 153:37–65
Labet M, Thielemans W (2009) Synthesis of polycaprolactone: a review. Chem Soc Rev 38:3484–3504
Mano JF, Gómez Ribelles JL, Alves NM, Salmerón Sanchez M (2005) Glass transition dynamics and structural relaxation of PLLA studied by DSC: influence of crystallinity. Polymer 46:8258–8265
Eckstein F, Lemberger B, Gratzke C, Hudelmaier M, Glaser C, Englmeier KH, Reiser M (2005) In vivo cartilage deformation after different types of activity and its dependence on physical training status. Ann Rheum Dis 64:291–295
Garlotta D (2001) A literature review of poly(lactic acid). J Polym Eng 9:63–84
Kovacs AJ, Aklonis JJ, Hutchinson JM, Ramos AR (1979) Isobaric volume and enthalpy recovery of glasses. II. A transparent multiparameter theory. J Polym Sci Polym Phys 17:1097–1162
Hernández F, Molina Mateo J, Romero Colomer F, Salmerón Sánchez M, Gómez Ribelles JL, Mano J (2005) Influence of low-temperature nucleation on the crystallization process of poly(l-lactide). Biomacromolecules 6:3291–3299
Wang Y, Gómez Ribelles JL, Salmerón Sánchez M, Mano JF (2005) Morphological contribution to glass transition in poly(l-lactic acid). Macromolecules 38:4712–4718
Salmerón Sánchez M, Vincent BM, Vanden Poel G, Gómez-Ribelles JL (2007) Effect of the cooling rate on the nucleation kinetics of poly(l-lactic acid) and its influence on morphology. Macromolecules 40:7989–7997
Nobuyuki O (1975) A threshold selection method from gray-level histograms. Automatica 11:23–27
Acknowledgements
The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the MAT2013-46467-C4-1-R project, including the Feder funds. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors thank “Servicio de Microscopia Electrónica” of Universitat Politècnica de València for their invaluable help. The translation of this paper was funded by the Universitat Politècnica de València, Spain.
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L. Vikingsson and A. Vinals-Guitart have contributed equally to this work.
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Vikingsson, L., Vinals-Guitart, A., Valera-Martínez, A. et al. Local deformation in a hydrogel induced by an external magnetic field. J Mater Sci 51, 9979–9990 (2016). https://doi.org/10.1007/s10853-016-0226-8
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DOI: https://doi.org/10.1007/s10853-016-0226-8