Abstract
Microfluidics techniques can be used to process a wide range of biomaterials, from synthetic to natural origin ones. This chapter describes microfluidic processing of biomaterials, mainly polymeric materials of natural origin, focusing on water-soluble polymers that form non-flowing phases after crosslinking. Some polysaccharides and proteins, including agarose, alginate, chitosan, gellan gum, hyaluronic acid, collagen, gelatin, and silk fibroin are emphasized deu to their relevance in the field. The critical characteristics of these materials are discussed, giving particular consideration to those that directly impact its processability using microfluidics. Furthermore, some microfluidic-based processing techniques are presented, describing their suitability to process materials with different sol-gel transition mechanisms.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Agnello S, Gasperini L, Reis RL, Mano JF, Pitarresi G, Palumbo FS, Giammona G (2016) Microfluidic production of hyaluronic acid derivative microfibers to control drug release. Mater Lett 182:309–313
Agnello S, Gasperini L, Mano JF, Pitarresi G, Palumbo FS, Reis RL, Giammona G (2017) Synthesis, mechanical and thermal rheological properties of new gellan gum derivatives. Int J Biol Macromol 98:646–653. https://doi.org/10.1016/j.ijbiomac.2017.02.029
Balazs EA (2004) Viscoelastic properties of hyaluronan and its therapeutic use. In: Chemistry and biology of hyaluronan, vol 415. Elsevier, Amsterdam
Barnes HHA, Barnes A (1997) Thixotropy – a review. Journal of Non-Newtonian Fluid Mechanics 70(97):1–33. https://doi.org/10.1016/S0377-0257(97)00004-9
Barnes HA, Walters K (1985) The yield stress myth? Rheol Acta 24(4):323–326. https://doi.org/10.1007/BF01333960
Bekturov EA, Bimedina LA (1981) Interpolymer complexes. Adv Polymer Sci 41:99–147
Carvalho AF, Gasperini L, Ribeiro RS, Marques AP, Reis R l (2017) Control of osmotic pressure to improve cell viability in cell-laden tissue engineering constructs. J Tissue Eng Regen Med 12(2):e1063–e1067. https://doi.org/10.1002/term.2432
Chen W, Kim J-H, Zhang D, Lee K-H, Cangelosi GA, Soelberg SD, Furlong CE, Chung J-H, Shen AQ (2013) Microfluidic one-step synthesis of alginate microspheres immobilized with antibodies. J R Soc, Interface R Soc 10:20130566. https://doi.org/10.1098/rsif.2013.0566
Cheng Y, Zheng F, Lu J, Shang L, Xie Z, Zhao Y, Chen Y, Gu Z (2014) Bioinspired multicompartmental microfibers from microfluidics. Adv Mater 26:5184–5190. https://doi.org/10.1002/adma.201400798
Choi C-H, Jung J-H, Rhee YW, Kim D-P, Shim S-E, Lee C-S (2007) Generation of monodisperse alginate microbeads and in situ encapsulation of cell in microfluidic device. Biomed Microdevices 9(6):855–862. https://doi.org/10.1007/s10544-007-9098-7
Costa-Almeida R, Gasperini L, Rodrigues MT, Babo PS, Mano JF, Reis RL, Gomes ME (2015) Development of biomimetic microengineered hydrogel fibers for tendon regeneration In 2015 4th TERMIS World Congress
Costa-Almeida R, Gasperini L, Borges J, Babo PS, Rodrigues MT, Mano JF, Reis RL, Gomes ME (2016) Microengineered multicomponent hydrogel fibers: combining polyelectrolyte complexation and microfluidics. ACS Biomat Sci Eng 3(7):1322–1331. https://doi.org/10.1021/acsbiomaterials.6b00331
Coutinho DF, Sant SV, Shin H, Oliveira JT, Gomes ME, Neves NM, Khademhosseini A, Reis RL (2010) Modified Gellan gum hydrogels with tunable physical and mechanical properties. Biomaterials 31(29):7494–7502. https://doi.org/10.1016/j.biomaterials.2010.06.035
Couto DS, Hong Z, Mano JF (2009) Development of bioactive and biodegradable chitosan-based injectable systems containing bioactive glass nanoparticles. Acta Biomater 5(1):115–123. https://doi.org/10.1016/j.actbio.2008.08.006
De Menech M, Garstecki P, Jousse F, Stone H a (2008) Transition from squeezing to dripping in a microfluidic T-shaped junction. J Fluid Mech 595:141–161. https://doi.org/10.1017/S002211200700910X
de Vos P, Faas MM, Strand B, Calafiore R (2006) Alginate-based microcapsules for immunoisolation of pancreatic islets. Biomaterials 27(32):5603–5617. https://doi.org/10.1016/j.biomaterials.2006.07.010
Drury JL, Dennis RG, Mooney DJ (2004) The tensile properties of alginate hydrogels. Biomaterials 25(16):3187–3199. https://doi.org/10.1016/j.biomaterials.2003.10.002
Ferreira P, Coelho, JFJ, Almeida JF, Gil MH (2009) Photocrosslinkable Polymers for Biomedical Applications. In R. Fazel (Ed.), Biomedical Engineering - Frontiers and Challenges. InTech, pp. 55–74
Gasperini L, Mano JF, Reis RL (2014) Natural polymers for the microencapsulation of cells. J R Soc Interface 11(100):20140817–20140817. https://doi.org/10.1098/rsif.2014.0817
Goh CH, Heng PWS, Chan LW (2012) Alginates as a useful natural polymer for microencapsulation and therapeutic applications. Carbohydr Polym 88(1):1–12. https://doi.org/10.1016/j.carbpol.2011.11.012
Grasdalen H, Smidsrød O (1987) Gelation of gellan gum. Carbohydr Polym 7(5):371–393. Retrieved from http://www.sciencedirect.com/science/article/pii/014486178790004X
Helseth DL, Veis A (1981) Collagen self-assembly in vitro differentiating specific telopeptide-dependent interactions using selective enzyme modification and the addition of free amino telopeptide. J Biol Chem 256(14):7118–7128. Retrieved from https://pdfs.semanticscholar.org/6d43/701ea790f272f10fdc437bcc8abfc79a38a5.pdf
Hirama H, Kambe T, Aketagawa K, Ota T, Moriguchi H, Torii T (2013) Hyper alginate gel microbead formation by molecular diffusion at the hydrogel/droplet interface. Langmuir: ACS J Surfaces Colloids 29(2):519–524. https://doi.org/10.1021/la303827u
Hu Y, Wang Q, Wang J, Zhu J, Wang H, Yang Y (2012) Shape controllable microgel particles prepared by microfluidic combining external ionic crosslinking. Biomicrofluidics 6(2):26502–265029. https://doi.org/10.1063/1.4720396
Indovina PL, Tettamanti E, Micciancio-Giammarinaro MS, Palma MU (1979) Thermal hysteresis and reversibility of gel-sol transition in agarose-water systems. J Chem Phys 70(6):2841–2847. https://doi.org/10.1063/1.437817
Jankowski P, Ogończyk D, Derzsi L, Lisowski W, Garstecki P (2013) Hydrophilic polycarbonate chips for generation of oil-in-water (O/W) and water-in-oil-in-water (W/O/W) emulsions. Microfluid Nanofluid 14(5):767–774. https://doi.org/10.1007/s10404-012-1090-8
Jeong B, Kim SW, Bae YH (2002) Thermosensitive sol-gel reversible hydrogels. Adv Drug Deliv Rev 54(1):37–51. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/11755705
Jun Y, Kang E, Chae S, Lee S-H (2014) Microfluidic spinning of micro- and nano-scale fibers for tissue engineering. Lab Chip 14(13):2145–2160. https://doi.org/10.1039/c3lc51414e
Kim U-J, Park J, Li C, Jin H-J, Valluzzi R, Kaplan DL (2004) Structure and properties of silk hydrogels. Biomacromolecules 5(3):786–792. https://doi.org/10.1021/bm0345460
Klouda L, Mikos AG (2008) Thermoresponsive hydrogels in biomedical applications. Eur J Pharm Biopharm: Off J Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik eV 68(1):34–45. https://doi.org/10.1016/j.ejpb.2007.02.025
Kuijpers AJ, Engbers GHM, Feijen J, De Smedt SC, Meyvis TKL, Demeester J, Krijgsveld J, Zaat SAJ, Dankert J (1999) Characterization of the network structure of Carbodiimide cross-linked gelatin gels. Macromolecules 32(10):3325–3333. https://doi.org/10.1021/ma981929v
Lahaye M, Rochas C (1991) Chemical structure and physico-chemical properties of agar. In: Juanes JA, Santelices B, McLachlan JL (eds) International workshop on Gelidium. Springer, Dordrecht, pp 137–148. https://doi.org/10.1007/978-94-011-3610-5
Lee C, Chang C, Wang Y, Fu L (2011) Microfluidic mixing: a review. Int J Mol Sci 12:3263–3287. https://doi.org/10.3390/ijms12053263
Mancini M, Moresi M, Rancini R (1999) Mechanical properties of alginate gels: empirical characterisation. J Food Eng 39:369–378. Retrieved from http://www.sciencedirect.com/science/article/pii/S0260877499000229
Mano JF, Silva GA, Azevedo HS, Malafaya PB, Sousa RA, Silva SS, Boesel LF, Oliveira JM, Santos TC, Marques AP, Neves NM, Reis RL (2007) Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends. J R Soc Interface 4(17):999–1030. https://doi.org/10.1098/rsif.2007.0220
Matsumoto A, Chen J, Collette AL, Kim U, Altman GH, Cebe P, Kaplan DL (2006) Mechanisms of silk fibroin sol-gel transitions. J Phys Chem B 110(43):21630–21638. https://doi.org/10.1021/jp056350v
Møller PCF, Mewis J, Bonn D (2006) Yield stress and thixotropy: on the difficulty of measuring yield stresses in practice. Soft Matter 2(4):274. https://doi.org/10.1039/b517840a
Moreira Teixeira LS, Feijen J, van Blitterswijk CA, Dijkstra PJ, Karperien M (2012) Enzyme-catalyzed crosslinkable hydrogels: emerging strategies for tissue engineering. Biomaterials 33(5):1281–1290. https://doi.org/10.1016/j.biomaterials.2011.10.067
Nguyen N-T, Wu Z (2005) Micromixers—a review. J Micromech Microeng 15(2):R1–R16. https://doi.org/10.1088/0960-1317/15/2/R01
Nie, Z., Seo, M., Xu, S., Lewis, P. C., Mok, M., Kumacheva, E., … Stone, H. a. (2008). Emulsification in a microfluidic flow-focusing device: effect of the viscosities of the liquids. Microfluid Nanofluid, 5, 585–594. doi:https://doi.org/10.1007/s10404-008-0271-y
Oliveira JT, Martins L, Picciochi R, Malafaya PB, Sousa RA, Neves NM, Mano JF, Reis RL (2010) Gellan gum: a new biomaterial for cartilage tissue engineering applications. J Biomed Mater Res A 93(3):852–863. https://doi.org/10.1002/jbm.a.32574
Rao MA (2007) Flow and functional models for rheological properties of fluid foods. Springer, Boston, pp 27–58. https://doi.org/10.1007/978-0-387-70930-7_2
Rinaudo M (2006) Chitin and chitosan: properties and applications. Prog Polym Sci 31(7):603–632. https://doi.org/10.1016/j.progpolymsci.2006.06.001
Rinaudo M, Pavlov G, Desbrie J (1999) Influence of acetic acid concentration on the solubilization of chitosan. Polymer 40:7029–7032
Saeki D, Sugiura S, Kanamori T, Sato S, Ichikawa S (2010) Microfluidic preparation of water-in-oil-in-water emulsions with an ultra-thin oil phase layer. Lab Chip 10(3):357–362. https://doi.org/10.1039/B916318B
Seemann R, Brinkmann M, Pfohl T, Herminghaus S (2011) Droplet based microfluidics. Rep Prog Phys 75:016601. https://doi.org/10.1088/0034-4885/75/1/016601
Šiljegović M, Kačarević-Popović ZM, Bibić N, Jovanović ZM, Maletić S, Stchakovsky M, Krklješ AN (2011) Optical and dielectric properties of fluorinated ethylene propylene and tetrafluoroethylene–perfluoro(alkoxy vinyl ether) copolymer films modified by low energy N4+ and C4+ ion beams. Radiat Phys Chem 80(12):1378–1385. https://doi.org/10.1016/J.RADPHYSCHEM.2011.08.012
Smeds KA, Grinstaff MW, Pfister-serres A, Miki D, Dastgheib K, Inoue M, Hatchell DL (2001) Photocrosslinkable polysaccharides for in situ hydrogel formation. J Biomed Mater Res 54(1):115–121
Sutera SP, Skalak R (1993) The history of Poiseuille’s law. Annu Rev Fluid Mech 25(1):1–20. https://doi.org/10.1146/annurev.fl.25.010193.000245
Tan W-H, Takeuchi S (2007) Monodisperse alginate hydrogel microbeads for cell encapsulation. Adv Mater 19(18):2696–2701. https://doi.org/10.1002/adma.200700433
Van Den Bulcke AI, Bogdanov B, De Rooze N, Schacht EH, Cornelissen M, Berghmans H (2000) Structural and rheological properties of Methacrylamide modified gelatin hydrogels. Biomacromolecules 1(1):31–38. https://doi.org/10.1021/bm990017d
Ward M, Georgiou TK (2011) Thermoresponsive polymers for biomedical applications. Polymers 3(4):1215–1242. https://doi.org/10.3390/polym3031215
Xu T, Molnar P, Gregory C, Das M, Boland T, Hickman JJ (2009) Electrophysiological characterization of embryonic hippocampal neurons cultured in a 3D collagen hydrogel. Biomaterials 30(26):4377–4383. https://doi.org/10.1016/j.biomaterials.2009.04.047
Zhang H, Tumarkin E, Peerani R, Nie Z, Sullan RMA, Walker GC, Kumacheva E (2006) Microfluidic production of biopolymer microcapsules with controlled morphology. J Am Chem Soc 128(37):12205–12210. https://doi.org/10.1021/ja0635682
Zhao LB, Pan L, Zhang K, Guo SS, Liu W, Wang Y, Chen Y, Zhao XZ, Chan HLW (2009) Generation of Janus alginate hydrogel particles with magnetic anisotropy for cell encapsulation. Lab Chip 9(20):2981–2986. https://doi.org/10.1039/b907478c
Acknowledgments
APM acknowledges the European Research Council for Consolidator Grant Project “ECM_INK” ERC-2016-COG-726061.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Gasperini, L., Marques, A.P., Reis, R.L. (2020). Microfluidics for Processing of Biomaterials. In: Oliveira, J., Reis, R. (eds) Biomaterials- and Microfluidics-Based Tissue Engineered 3D Models. Advances in Experimental Medicine and Biology, vol 1230. Springer, Cham. https://doi.org/10.1007/978-3-030-36588-2_2
Download citation
DOI: https://doi.org/10.1007/978-3-030-36588-2_2
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-36587-5
Online ISBN: 978-3-030-36588-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)