Abstract
In embryonic development, pure cartilage structures are in the basis of bone-cartilage interfaces. Despite this fact, the mature bone and cartilage structures can vary greatly in composition and function. Nevertheless, they collaborate in the osteochondral region to create a smooth transition zone that supports the movements and forces resulting from the daily activities. In this sense, all the hierarchical organization is involved in the maintenance and reestablishment of the equilibrium in case of damage. Therefore, this interface has attracted a great deal of interest in order to understand the mechanisms of regeneration or disease progression in osteoarthritis. With that purpose, in vitro tissue models (either static or dynamic) have been studied. Static in vitro tissue models include monocultures, co-cultures, 3D cultures, and ex vivo cultures, mostly cultivated in flat surfaces, while dynamic models involve the use of bioreactors and microfluidic systems. The latter have emerged as alternatives to study the cellular interactions in a more authentic manner over some disadvantages of the static models. The current alternatives of in vitro mimetic models for bone-cartilage interface regeneration are overviewed and discussed herein.
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References
Hoemann CD, Lafantaisie-Favreau C-H, Lascau-Coman V et al (2012) The cartilage-bone interface. J Knee Surg 25:85–97. https://doi.org/10.1055/s-0032-1319782
Haines RW (1975) The histology of epiphyseal union in mammals. J Anat 120:1–25
Hunziker EB, Kapfinger E, Geiss J (2007) The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development. Osteoarthr Cartil 15:403–413. https://doi.org/10.1016/j.joca.2006.09.010
Hayes AJ, MacPherson S, Morrison H et al (2001) The development of articular cartilage: evidence for an appositional growth mechanism. Anat Embryol (Berl) 203:469–479
Khanarian NT, Boushell MK, Spalazzi JP et al (2014) FTIR-I compositional mapping of the cartilage-to-bone Interface as a function of tissue region and age. J Bone Miner Res 29:2643–2652. https://doi.org/10.1002/jbmr.2284
Yang L, Tsang KY, Tang HC et al (2014) Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation. Proc Natl Acad Sci U S A 111:12097–12102. https://doi.org/10.1073/pnas.1302703111
Atesok K, Doral MN, Karlsson J et al (2016) Multilayer scaffolds in orthopaedic tissue engineering. Knee Surgery, Sport Traumatol Arthrosc 24:2365–2373. https://doi.org/10.1007/s00167-014-3453-z
Liu Y, Lian Q, He J et al (2011) Study on the microstructure of human articular cartilage/bone Interface. J Bionic Eng 8:251–262. https://doi.org/10.1016/S1672-6529(11)60037-1
Goldring SR, Goldring MB (2016) Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage–bone cross talk. Nat Rev Rheumatol 12:632–644. https://doi.org/10.1038/nrrheum.2016.148
Mithoefer K, McAdams TR, Scopp JM, Mandelbaum BR (2009) Emerging options for treatment of articular cartilage injury in the athlete. Clin Sports Med 28:25–40. https://doi.org/10.1016/j.csm.2008.09.001
Smith GD, Knutsen G, Richardson JB (2005) A clinical review of cartilage repair techniques. J Bone Jt Surg - Br 87–B:445–449. https://doi.org/10.1302/0301-620X.87B4.15971
Iqbal Z, Kumaraswamy V, Srivastava P et al (2013) Role of autologous chondrocyte transplantation in articular cartilage defects: an experimental study. Indian J Orthop 47:129. https://doi.org/10.4103/0019-5413.108878
Röhner E, Pfitzner T, Preininger B et al (2016) Temporary arthrodesis using fixator rods in two-stage revision of septic knee prothesis with severe bone and tissue defects. Knee Surgery, Sport Traumatol Arthrosc 24:84–88. https://doi.org/10.1007/s00167-014-3324-7
Siclari A, Mascaro G, Gentili C et al (2014) Cartilage repair in the knee with subchondral drilling augmented with a platelet-rich plasma-immersed polymer-based implant. Knee Surgery, Sport Traumatol Arthrosc 22:1225–1234. https://doi.org/10.1007/s00167-013-2484-1
Alexander PG, Gottardi R, Lin H et al (2014) Three-dimensional osteogenic and chondrogenic systems to model osteochondral physiology and degenerative joint diseases. Exp Biol Med 239:1080–1095. https://doi.org/10.1177/1535370214539232
Worthen J, Waterman BR, Davidson PA, Lubowitz JH (2012) Limitations and sources of bias in clinical knee cartilage research. Arthrosc J Arthrosc Relat Surg 28:1315–1325. https://doi.org/10.1016/j.arthro.2012.02.022
Johnson CI, Argyle DJ, Clements DN (2016) In vitro models for the study of osteoarthritis. Vet J 209:40–49. https://doi.org/10.1016/j.tvjl.2015.07.011
Gibson JS, Milner PI, White R et al (2007) Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis. Pflügers Arch - Eur J Physiol 455:563–573. https://doi.org/10.1007/s00424-007-0310-7
Grimshaw MJ, Mason RM (2001) Modulation of bovine articular chondrocyte gene expression in vitro by oxygen tension. Osteoarthr Cartil 9:357–364. https://doi.org/10.1053/joca.2000.0396
Murphy CL, Sambanis A (2001) Effect of oxygen tension and alginate encapsulation on restoration of the differentiated phenotype of passaged chondrocytes. Tissue Eng 7:791–803. https://doi.org/10.1089/107632701753337735
Yang PJ, Temenoff JS (2009) Engineering Orthopedic tissue interfaces. Tissue Eng Part B Rev 15:127–141. https://doi.org/10.1089/ten.teb.2008.0371
Madry H, Luyten FP, Facchini A (2012) Biological aspects of early osteoarthritis. Knee Surgery, Sport Traumatol Arthrosc 20:407–422. https://doi.org/10.1007/s00167-011-1705-8
Butler LM, McGettrick HM, Nash GB (2016) Static and dynamic assays of cell adhesion relevant to the vasculature. Methods Mol Biol 1430:231–248
Elliott NT, Yuan F (2011) A review of three-dimensional in vitro tissue models for drug discovery and transport studies. J Pharm Sci 100:59–74. https://doi.org/10.1002/jps.22257
Duval K, Grover H, Han L-H et al (2017) Modeling physiological events in 2D vs. 3D cell culture. Physiology 32:266–277. https://doi.org/10.1152/physiol.00036.2016
Sailon AM, Allori AC, Davidson EH et al (2009) A novel flow-perfusion bioreactor supports 3D dynamic cell culture. J Biomed Biotechnol 2009:873816. https://doi.org/10.1155/2009/873816
Umansky R (1966) The effect of cell population density on the developmental fate of reaggregating mouse limb bud mesenchyme. Dev Biol 13:31–56. https://doi.org/10.1016/0012-1606(66)90048-0
Sanchez C, Deberg MA, Bellahcène A et al (2008) Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritic subchondral bone. Arthritis Rheum 58:442–455. https://doi.org/10.1002/art.23159
Hunter GK, Hauschka PV, Poole AR et al (1996) Nucleation and inhibition of hydroxyapatite formation by mineralized tissue proteins. Biochem J 317(Pt 1):59–64
Greco KV, Iqbal AJ, Rattazzi L et al (2011) High density micromass cultures of a human chondrocyte cell line: a reliable assay system to reveal the modulatory functions of pharmacological agents. Biochem Pharmacol 82:1919–1929. https://doi.org/10.1016/j.bcp.2011.09.009
Ahrens PB, Solursh M, Reiter RS (1977) Stage-related capacity for limb chondrogenesis in cell culture. Dev Biol 60:69–82
Jähn K, Richards RG, Archer CW, Stoddart MJ (2010) Pellet culture model for human primary osteoblasts. Eur Cell Mater 20:149–161. doi: vol020a13 [pii]
Kirkpatrick CJ, Fuchs S, Unger RE (2011) Co-culture systems for vascularization — learning from nature. Adv Drug Deliv Rev 63:291–299. https://doi.org/10.1016/j.addr.2011.01.009
Genova T, Munaron L, Carossa S, Mussano F (2016) Overcoming physical constraints in bone engineering: “the importance of being vascularized”. J Biomater Appl 30:940–951. https://doi.org/10.1177/0885328215616749
Pirraco RP, Marques AP, Reis RL (2010) Cell interactions in bone tissue engineering. J Cell Mol Med 14:93–102. https://doi.org/10.1111/j.1582-4934.2009.01005.x
Lee P, Tran K, Zhou G et al (2015) Guided differentiation of bone marrow stromal cells on co-cultured cartilage and bone scaffolds. Soft Matter 11:7648–7655. https://doi.org/10.1039/C5SM01909E
Mesallati T, Sheehy EJ, Vinardell T et al (2015) Tissue engineering scaled-up, anatomically shaped osteochondral constructs for joint resurfacing. Eur Cell Mater 30:163–185
Baldwin J, Antille M, Bonda U et al (2014) In vitro pre-vascularisation of tissue-engineered constructs a co-culture perspective. Vasc Cell 6:1–16. https://doi.org/10.1186/2045-824X-6-13
Hubka KM, Dahlin RL, Meretoja VV et al (2014) Enhancing Chondrogenic phenotype for cartilage tissue engineering: monoculture and co-culture of articular chondrocytes and mesenchymal stem cells. Tissue Eng Part B 20:1–50. https://doi.org/10.1089/ten.TEB.2014.0034
Meretoja VV, Dahlin RL, Wright S et al (2013) The effect of hypoxia on the chondrogenic differentiation of co-cultured articular chondrocytes and mesenchymal stem cells in scaffolds. Biomaterials 34:4266–4273. https://doi.org/10.1016/j.biomaterials.2013.02.064
Wu L, Leijten JCH, Georgi N et al (2011) Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation. Tissue Eng Part A 17:1425–1436. https://doi.org/10.1089/ten.TEA.2010.0517
Ahmed N, Gan L, Nagy A et al (2009) Cartilage tissue formation using Redifferentiated passaged chondrocytes in vitro. Tissue Eng Part A 15:665–673. https://doi.org/10.1089/ten.tea.2008.0004
Qing C, Wei-ding C, Wei-min F (2011) Co-culture of chondrocytes and bone marrow mesenchymal stem cells in vitro enhances the expression of cartilaginous extracellular matrix components. Brazilian J Med Biol Res = Rev Bras Pesqui medicas e Biol 44:303–310
Olivos-Meza A, Velasquillo Martínez C, Olivos Díaz B et al (2017) Co-culture of dedifferentiated and primary human chondrocytes obtained from cadaveric donor enhance the histological quality of repair tissue: an in-vivo animal study. Cell Tissue Bank 18:369–381. https://doi.org/10.1007/s10561-017-9635-4
Zhong J, Guo B, Xie J et al (2016) Crosstalk between adipose-derived stem cells and chondrocytes: when growth factors matter. Bone Res 4:15036. https://doi.org/10.1038/boneres.2015.36
ter Huurne M, Schelbergen R, Blattes R et al (2012) Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum 64:3604–3613. https://doi.org/10.1002/art.34626
Schulze S, Wehrum D, Dieter P, Hempel U (2017) A supplement-free osteoclast-osteoblast co-culture for pre-clinical application. J Cell Physiol. https://doi.org/10.1002/jcp.26076
Janardhanan S, Wang MO, Fisher JP (2012) Coculture strategies in bone tissue engineering: the impact of culture conditions on pluripotent stem cell populations. Tissue Eng Part B Rev 18:312–321. https://doi.org/10.1089/ten.TEB.2011.0681
Panseri S, Russo A, Cunha C et al (2012) Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration. Knee Surgery, Sport Traumatol Arthrosc 20:1182–1191. https://doi.org/10.1007/s00167-011-1655-1
Pesesse L, Sanchez C, Henrotin Y (2011) Osteochondral plate angiogenesis: a new treatment target in osteoarthritis. Jt Bone Spine 78:144–149. https://doi.org/10.1016/j.jbspin.2010.07.001
Gawlitta D, Farrell E, Malda J et al (2010) Modulating endochondral ossification of multipotent stromal cells for bone regeneration. Tissue Eng Part B Rev 16:385–395. https://doi.org/10.1089/ten.TEB.2009.0712
Tokuhara Y, Wakitani S, Imai Y et al (2010) Repair of experimentally induced large osteochondral defects in rabbit knee with various concentrations of Escherichia coli-derived recombinant human bone morphogenetic protein-2. Int Orthop 34:761–767. https://doi.org/10.1007/s00264-009-0818-x
UNGER R, SARTORIS A, PETERS K et al (2007) Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials. Biomaterials 28:3965–3976. https://doi.org/10.1016/j.biomaterials.2007.05.032
Goerke SM, Plaha J, Hager S et al (2012) Human endothelial progenitor cells induce extracellular signal-regulated kinase-dependent differentiation of mesenchymal stem cells into smooth muscle cells upon Cocultivation. Tissue Eng Part A 18:120914061009005. https://doi.org/10.1089/ten.tea.2012.0147
Davis GE, Bayless KJ, Mavila A (2002) Molecular basis of endothelial cell morphogenesis in three-dimensional extracellular matrices. Anat Rec 268:252–275. https://doi.org/10.1002/ar.10159
Davis GE, Stratman AN, Sacharidou A, Koh W (2011) Molecular basis for endothelial lumen formation and Tubulogenesis during Vasculogenesis and Angiogenic sprouting. Int Rev Cell Mol Biol 288:101–165. https://doi.org/10.1016/B978-0-12-386041-5.00003-0
Evensen L, Micklem DR, Blois A et al (2009) Mural cell associated VEGF is required for Organotypic vessel formation. PLoS One 4:e5798. https://doi.org/10.1371/journal.pone.0005798
Kim K-I, Park S, Im G-I (2014) Osteogenic differentiation and angiogenesis with cocultured adipose-derived stromal cells and bone marrow stromal cells. Biomaterials 35:4792–4804. https://doi.org/10.1016/j.biomaterials.2014.02.048
Pepper MS, Montesano R, Vassalli J-D, Orci L (1991) Chondrocytes inhibit endothelial sprout formation in vitro: evidence for involvement of a transforming growth factor-beta. J Cell Physiol 146:170–179. https://doi.org/10.1002/jcp.1041460122
Yuan XL, Meng HY, Wang YC et al (2014) Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies. Osteoarthr Cartil 22:1077–1089. https://doi.org/10.1016/j.joca.2014.05.023
Pan J, Wang B, Li W et al (2012) Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints. Bone 51:212–217. https://doi.org/10.1016/j.bone.2011.11.030
Pan J, Zhou X, Li W et al (2009) In situ measurement of transport between subchondral bone and articular cartilage. J Orthop Res 27:1347–1352. https://doi.org/10.1002/jor.20883
Jiang J, Leong NL, Mung JC et al (2008) Interaction between zonal populations of articular chondrocytes suppresses chondrocyte mineralization and this process is mediated by PTHrP. Osteoarthr Cartil 16:70–82. https://doi.org/10.1016/j.joca.2007.05.014
Çakmak S, Çakmak AS, Kaplan DL, Gümüşderelioğlu M (2016) A silk fibroin and peptide Amphiphile-based co-culture model for osteochondral tissue engineering. Macromol Biosci 16:1212–1226. https://doi.org/10.1002/mabi.201600013
Farrell E, Both SK, Odörfer KI et al (2011) In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells. BMC Musculoskelet Disord 12:31. https://doi.org/10.1186/1471-2474-12-31
Janicki P, Kasten P, Kleinschmidt K et al (2010) Chondrogenic pre-induction of human mesenchymal stem cells on β-TCP: enhanced bone quality by endochondral heterotopic bone formation. Acta Biomater 6:3292–3301. https://doi.org/10.1016/j.actbio.2010.01.037
Scotti C, Piccinini E, Takizawa H et al (2013) Engineering of a functional bone organ through endochondral ossification. Proc Natl Acad Sci 110:3997–4002. https://doi.org/10.1073/pnas.1220108110
Panseri S, Montesi M, Dozio SM et al (2016) Biomimetic scaffold with aligned microporosity designed for dentin regeneration. Front Bioeng Biotechnol 4:48. https://doi.org/10.3389/fbioe.2016.00048
Font Tellado S, Bonani W, Balmayor ER et al (2017) Fabrication and characterization of biphasic silk fibroin scaffolds for tendon/ligament-to-bone tissue engineering. Tissue Eng Part A 23:859–872. https://doi.org/10.1089/ten.tea.2016.0460
O’Shea TM, Miao X (2008) Bilayered scaffolds for osteochondral tissue engineering. Tissue Eng Part B Rev 14:447–464. https://doi.org/10.1089/ten.teb.2008.0327
Oliveira JM, Rodrigues MT, Silva SS et al (2006) Novel hydroxyapatite/chitosan bilayered scaffold for osteochondral tissue-engineering applications: scaffold design and its performance when seeded with goat bone marrow stromal cells. Biomaterials 27:6123–6137. https://doi.org/10.1016/J.BIOMATERIALS.2006.07.034
Yan L-P, Silva-Correia J, Oliveira MB et al (2015) Bilayered silk/silk-nanoCaP scaffolds for osteochondral tissue engineering: in vitro and in vivo assessment of biological performance. Acta Biomater 12:227–241. https://doi.org/10.1016/j.actbio.2014.10.021
Kang H, Peng J, Lu S et al (2014) In vivo cartilage repair using adipose-derived stem cell-loaded decellularized cartilage ECM scaffolds. J Tissue Eng Regen Med 8:442–453. https://doi.org/10.1002/term.1538
Zheng X-F, Lu S-B, Zhang W-G et al (2011) Mesenchymal stem cells on a decellularized cartilage matrix for cartilage tissue engineering. Biotechnol Bioprocess Eng 16:593–602. https://doi.org/10.1007/s12257-010-0348-9
Sutherland AJ, Beck EC, Dennis SC et al (2015) Decellularized cartilage may be a Chondroinductive material for osteochondral tissue engineering. PLoS One 10:e0121966. https://doi.org/10.1371/journal.pone.0121966
Johnson CC, Johnson DJ, Garcia GH et al (2017) High short-term failure rate associated with Decellularized osteochondral allograft for treatment of knee cartilage lesions. Arthrosc J Arthrosc Relat Surg. https://doi.org/10.1016/j.arthro.2017.07.018
Vindas Bolaños RA, Cokelaere SM, Estrada McDermott JM et al (2017) The use of a cartilage decellularized matrix scaffold for the repair of osteochondral defects: the importance of long-term studies in a large animal model. Osteoarthr Cartil 25:413–420. https://doi.org/10.1016/j.joca.2016.08.005
Do A-V, Khorsand B, Geary SM, Salem AK (2015) 3D printing of scaffolds for tissue regeneration applications. Adv Healthc Mater 4:1742–1762. https://doi.org/10.1002/adhm.201500168
JoVE Science Education Database. Developmental Biology. Explant Culture for Developmental Studies. JoVE, Cambridge, MA, (2018). https://www.jove.com/science-education/5329/explant-culture-fordevelopmental-studies. Accessed 22 Sep 2017
Marino S, Staines KA, Brown G et al (2016) Models of ex vivo explant cultures: applications in bone research. Bonekey Rep. https://doi.org/10.1038/bonekey.2016.49
Madsen SH, Goettrup AS, Thomsen G et al (2011) Characterization of an ex vivo femoral head model assessed by markers of bone and cartilage turnover. Cartilage 2:265–278. https://doi.org/10.1177/1947603510383855
de Vries-van Melle ML, Mandl EW, Kops N et al (2012) An osteochondral culture model to study mechanisms involved in articular cartilage repair. Tissue Eng Part C Methods 18:45–53. https://doi.org/10.1089/ten.TEC.2011.0339
You J, Yellowley CE, Donahue HJ et al (2000) Substrate deformation levels associated with routine physical activity are less stimulatory to bone cells relative to loading-induced oscillatory fluid flow. J Biomech Eng 122:387–393
Yeatts AB, Fisher JP (2011) Bone tissue engineering bioreactors: dynamic culture and the influence of shear stress. Bone 48:171–181. https://doi.org/10.1016/j.bone.2010.09.138
Grayson WL, Bhumiratana S, Grace Chao PH et al (2010) Spatial regulation of human mesenchymal stem cell differentiation in engineered osteochondral constructs: effects of pre-differentiation, soluble factors and medium perfusion. Osteoarthr Cartil 18:714–723. https://doi.org/10.1016/j.joca.2010.01.008
Malafaya PB, Reis RL (2009) Bilayered chitosan-based scaffolds for osteochondral tissue engineering: influence of hydroxyapatite on in vitro cytotoxicity and dynamic bioactivity studies in a specific double-chamber bioreactor. Acta Biomater 5:644–660. https://doi.org/10.1016/j.actbio.2008.09.017
R, Canadas (2015) Oliveira JM. Marques AP RR, Multi-chambers bioreactor, methods and uses
Canadas R, Oliveira JM, Marques AP RR (2014) Rotational dual chamber bioreactor: methods and uses thereof
Lozito TP, Alexander PG, Lin H et al (2013) Three-dimensional osteochondral microtissue to model pathogenesis of osteoarthritis. Stem Cell Res Ther 4:S6. https://doi.org/10.1186/scrt367
Responte DJ, Lee JK, Hu JC, Athanasiou KA (2012) Biomechanics-driven chondrogenesis: from embryo to adult. FASEB J 26:3614–3624. https://doi.org/10.1096/fj.12-207241
Oftadeh R, Perez-Viloria M, Villa-Camacho JC et al (2015) Biomechanics and mechanobiology of trabecular bone: a review. J Biomech Eng 137:108021. https://doi.org/10.1115/1.4029176
Elder S, Fulzele K, McCulley W (2005) Cyclic hydrostatic compression stimulates chondroinduction of C3H/10T1/2 cells. Biomech Model Mechanobiol 3:141–146. https://doi.org/10.1007/s10237-004-0058-3
Gaspar DA, Gomide V, Monteiro FJ (2012) The role of perfusion bioreactors in bone tissue engineering. Biomatter 2:167–175. https://doi.org/10.4161/biom.22170
Amini AR, Laurencin CT, Nukavarapu SP (2012) Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 40:363–408
Sackmann EK, Fulton AL, Beebe DJ (2014) The present and future role of microfluidics in biomedical research. Nature 507:181–189. https://doi.org/10.1038/nature13118
Zhang J, Wei X, Zeng R et al (2017) Stem cell culture and differentiation in microfluidic devices toward organ-on-a-chip. Futur Sci OA 3:FSO187. https://doi.org/10.4155/fsoa-2016-0091
Jun Y, Kang E, Chae S, Lee S-H (2014) Microfluidic spinning of micro- and nano-scale fibers for tissue engineering. Lab Chip 14:2145–2160. https://doi.org/10.1039/C3LC51414E
Hasan A, Paul A, Vrana NE et al (2014) Microfluidic techniques for development of 3D vascularized tissue. Biomaterials 35:7308–7325. https://doi.org/10.1016/j.biomaterials.2014.04.091
Aroonnual A, Janvilisri T, Ounjai P, Chankhamhaengdecha S (2017) Microfluidics: innovative approaches for rapid diagnosis of antibiotic-resistant bacteria. Essays Biochem 61:91–101. https://doi.org/10.1042/EBC20160059
Goldman SM, Barabino GA (2016) Spatial engineering of osteochondral tissue constructs through Microfluidically directed differentiation of mesenchymal stem cells. Biores Open Access 5:109–117. https://doi.org/10.1089/biores.2016.0005
Kim KM, Choi YJ, Hwang J-H et al (2014) Shear stress induced by an interstitial level of slow flow increases the osteogenic differentiation of mesenchymal stem cells through TAZ activation. PLoS One 9:e92427. https://doi.org/10.1371/journal.pone.0092427
Hasani-Sadrabadi MM, Pour Hajrezaei S, Hojjati Emami S et al (2015) Enhanced osteogenic differentiation of stem cells via microfluidics synthesized nanoparticles. Nanomedicine Nanotechnology, Biol Med 11:1809–1819. https://doi.org/10.1016/j.nano.2015.04.005
Whitesides GM (2006) The origins and the future of microfluidics. Nature 442:368–373. https://doi.org/10.1038/nature05058
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The research leading to this work has received funding from the Portuguese Foundation for Science and Technology for the M-ERA.NET/0001/2014 project and for the funds provided under the program Investigador FCT 2012 and 2015 (IF/00423/2012 and IF/01285/2015).
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Bicho, D., Pina, S., Oliveira, J.M., Reis, R.L. (2018). In Vitro Mimetic Models for the Bone-Cartilage Interface Regeneration. In: Oliveira, J., Pina, S., Reis, R., San Roman, J. (eds) Osteochondral Tissue Engineering. Advances in Experimental Medicine and Biology, vol 1059. Springer, Cham. https://doi.org/10.1007/978-3-319-76735-2_17
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