Osteosarcoma growth on trabecular bone mimicking structures manufactured via laser direct write

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Atra Malayeri, Colin Sherborne, Thomas Paterson, Shweta Mittar, Ilida Ortega Asencio, Paul V. Hatton, Frederik Claeyssens


This paper describes the direct laser write of a photocurable acrylate-based PolyHIPE (High Internal Phase Emulsion) to produce scaffolds with both macro- and microporosity, and the use of these scaffolds in osteosarcoma-based 3D cell culture. The macroporosity was introduced via the application of stereolithography to produce a classical woodpile structure with struts having an approximate diameter of 200 m and pores were typically around 500 m in diameter. The PolyHIPE retained its microporosity after stereolithographic manufacture, with a range of pore sizes typically between 10 and 60 m (with most pores between 20 and 30 m). The resulting scaffolds were suitable substrates for further modification using acrylic acid plasma polymerisation. This scaffold was used as a structural mimic of the trabecular bone and in vitro determination of biocompatibility using cultured bone cells (MG63) demonstrated that cells were able to colonise all materials tested, with evidence that acrylic acid plasma polymerisation improved biocompatibility in the long term. The osteosarcoma cell culture on the 3D printed scaffold exhibits different growth behaviour than observed on tissue culture plastic or a flat disk of the porous material; tumour spheroids are observed on parts of the scaffolds. The growth of these spheroids indicates that the osteosarcoma behave more akin to in vivo in this 3D mimic of trabecular bone. It was concluded that PolyHIPEs represent versatile biomaterial systems with considerable potential for the manufacture of complex devices or scaffolds for regenerative medicine. In particular, the possibility to readily mimic the hierarchical structure of native tissue enables opportunities to build in vitro models closely resembling tumour tissue.


high internal phase emulsion; PolyHIPEs; scaffold; emulsion templating; photopolymerisation; bone cells; MG63

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Bokhari M, Carnachan R J, Przyborski S A, et al., 2007, Emulsion-templated porous polymers as scaffolds for three dimensional cell culture: effect of synthesis parameters on scaffold formation and homogeneity. Journal of Materials Chemistry, vol.17(38): 4088–4094. http://dx.doi.org/10.1039/B707499A

Kimmins S D and Cameron N R, 2011, Functional porous polymers by emulsion templating: recent advances. Advanced Functional Materials, vol.21(2): 211–225. http://dx.doi.org/10.1002/adfm.201001330

Barbetta A and Cameron N R, 2004, Morphology and surface area of emulsion-derived (PolyHIPE) solid foams prepared with oil-phase soluble porogenic solvents: span 80 as surfactant. Macromolecules, vol.37(9): 3188–3201. http://dx.doi.org/10.1021/ma0359436

Kimmins S D, Wyman P and Cameron N R, 2012, Photopolymerised methacrylate-based emulsion-templated porous polymers. Reactive and Functional Polymers, vol.72(12): 947–954. http://dx.doi.org/10.1016/j.reactfunctpolym.2012.06.015

Foudazi R, Gokun P, Feke D L, et al., 2013, Chemorheology of Poly(high internal phase emulsions). Macromolecules, vol.46(13): 5393–5396. http://dx.doi.org/10.1021/ma401157b

Gitli T and Silverstein M S, 2008, Bicontinuous hydrogel-hydrophobic polymer systems through emulsion templated simultaneous polymerizations. Soft Matter, vol.4(12): 2475–2485. http://dx.doi.org/10.1039/B809346F

Moghbeli M R and Shahabi M, 2011, Morphology and mechanical properties of an elastomeric poly(HIPE) nanocomposite foam prepared via an emulsion template. Iranian Polymer Journal, vol.20(5): 343–355.

Cummins D, Wyman P, Duxbury C J, et al., 2007, Synthesis of functional photopolymerized macroporous polyHIPEs by atom transfer radical polymerization surface grafting. Chemistry of Materials, vol.19(22): 5285–5292. http://dx.doi.org/10.1021/cm071511o

Hayward A S, Sano N, Przyborski S A, et al. 2013, Acrylic-acid-functionalized PolyHIPE scaffolds for use in 3D cell culture. Macromolecular Rapid Communications, vol.34(23–24): 1844–1849. http://dx.doi.org/10.1002/marc.201300709

Pierre S J, Thies J C, Dureault A, et al., 2006, Covalent enzyme immobilization onto photopolymerized highly porous monoliths. Advanced Materials, vol.18(14): 1822–1826. http://dx.doi.org/10.1002/adma.200600293

Sušec M, Ligon S C, Stampfl J, et al., 2013, Hierarchically porous materials from layer-by-layer photopolymerization of high internal phase emulsions. Macromolecular Rapid Communications, vol.34(11): 938–943. http://dx.doi.org/10.1002/marc.201300016

Caldwell S, Johnson D W, Didsbury M P, et al., 2012, Degradable emulsion-templated scaffolds for tissue engineering from thiol-ene photopolymerisation. Soft Matter, vol. 8(40): 10344–10351. http://dx.doi.org/10.1039/C2SM26250A

Johnson D W, Sherborne C, Didsbury M P, et al., 2013, Macrostructuring of emulsion-templated porous polymers by 3D laser patterning. Advanced Materials, vol.25(23): 3178–3181. http://dx.doi.org/10.1002/adma.201300552

Lovelady E, Kimmins S D, Wu J, et al., 2011, Preparation of emulsion-templated porous polymers using thiol-ene and thiol-yne chemistry. Polymer Chemistry, vol.2(3): 559–562. http://dx.doi.org/10.1039/C0PY00374C

Huš S and Krajnc P, 2014, PolyHIPEs from methyl methacrylate: hierarchically structured microcellular polymers with exceptional mechanical properties. Polymer, vol.55(17): 4420–4424. http://dx.doi.org/10.1016/j.polymer.2014.07.007

Causa F, Netti P A and Ambrosio L, 2007, A multi-functional scaffold for tissue regeneration: the need to engineer a tissue analogue. Biomaterials, vol.28(34): 5093–5099. http://dx.doi.org/10.1016/j.biomaterials.2007.07.030

Griffith L G and Swartz M A, 2006, Capturing complex 3D tissue physiology in vitro. Nature Reviews Molecular Cell Biology, vol.7: 211–224. http://dx.doi.org/10.1038/nrm1858

Dalton P D, Vaquette C, Farrugia B L, et al., 2013, Electrospinning and additive manufacturing: converging technologies. Biomaterials Science, vol.1: 171–185. http://dx.doi.org/10.1039/C2BM00039C

Ortega I, Ryan A J, Deshpande P, et al., 2013, Combined microfabrication and electrospinning to produce 3-D architectures for corneal repair. Acta Biomaterialia, vol.9(3): 5511–5520. http://dx.doi.org/10.1016/j.actbio.2012.10.039

Lee M, Dunn J C Y and Wu B M, 2005, Scaffold fabrication by indirect three-dimensional printing. Biomaterials, vol.26(20): 4281–4289. http://dx.doi.org/10.1016/j.biomaterials.2004.10.040

Mohanty S, Sanger K, Heiskanen A, et al., 2016, Fabrication of scalable tissue engineering scaffolds with dual-pore microarchitecture by combining 3D printing and particle leaching. Materials Science and Engineering: C, vol.61: 180–189. http://dx.doi.org/10.1016/j.msec.2015.12.032

Ortega I, Dew L, Kelly A G, et al., 2015, Fabrication of biodegradable synthetic perfusable vascular networks via a combination of electrospinning and robocasting. Biomaterials Science, vol.3(4): 592–596. http://dx.doi.org/10.1039/C4BM00418C

Jeffries E M, Nakamura S, Lee K W, et al., 2014, Micropatterning electrospun scaffolds to create intrinsic vascular networks. Macromolecular Bioscience, vol.14(11): 1514–1520. http://dx.doi.org/10.1002/mabi.201400306

Owen R, Sherborne C, Paterson T, et al., 2015, Emulsion templated scaffolds with tunable mechanical properties for bone tissue engineering. Journal of Mechanical Behavior of Biomedical Materials, vol.54: 159–172. http://dx.doi.org/10.1016/j.jmbbm.2015.09.019

Wang A, Paterson T, Owen R, et al., 2016, Photocurable high internal phase emulsions (HIPEs) containing hydroxyapatite for additive manufacture of tissue engineering scaffolds with multi-scale porosity. Materials Sci-ence and Engineering: C, vol.67: 51–58. http://dx.doi.org/10.1016/j.msec.2016.04.087

Lumelsky Y, Lalush-Michael I, Levenberg S, et al., 2009, A degradable, porous, emulsion-templated polyacrylate. Journal of Polymer Science Part A Polymer Chemistry, vol.47(24): 7043–7053. http://dx.doi.org/10.1002/pola.23744

Silverstein M S, 2014, Emulsion-templated porous polymers: a retrospective perspective. Polymer, vol.55(1): 304–320. http://dx.doi.org/10.1016/j.polymer.2013.08.068

Chen P Y and McKittrick J, 2011, Compressive mechanical properties of demineralized and deproteinized cancellous bone. Journal of Mechanical Behavior of Biomedical Materials, vol.4(7): 961–973. http://dx.doi.org/10.1016/j.jmbbm.2011.02.006

Santini M T, Rainaldi G, Romano R, et al., 2004, MG-63 human osteosarcoma cells grown in monolayer and as three-dimensional tumor spheroids present a different metabolic profile: a 1H NMR study. FEBS Letters, vol.557(1–3): 148–154. http://dx.doi.org/10.1016/S0014-5793(03)01466-2

Trojani C, Weiss P, Michiels J F, et al., 2005, Three-dimensional culture and differentiation of human osteogenic cells in an injectable hydroxypropylmethylcellulose hydrogel. Biomaterials, vol.26(27): 5509–5517. http://dx.doi.org/10.1016/j.biomaterials.2005.02.001

Kale S, Biermann S, Edwards C, et al., 2000, Three-dimensional cellular development is essential for ex vivo formation of human bone. Nature Biotechnology, vol.18: 954–958. http://dx.doi.org/10.1038/79439

DOI: http://dx.doi.org/10.18063/IJB.2016.02.005


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