Abstract
Alginate beads have been a popular carrier of a wide array of biologically relevant molecules, such as proteins, genes, and cells, for biomedical applications. However, the difficulty of controlling their mechanical properties as well as maintaining the long-term structural integrity has prevented more widespread utilization. Herein, a simple yet highly efficient method of engineering alginate beads with improved mechanical properties is presented, whereby a secondary network of biocompatible anionic cellulose is created within the alginate network. The aqueous-soluble anionic cellulose, containing either carboxylate or sulfonate, is found to undergo crosslinking reaction with trivalent ions more favorably than divalent ions, necessitating a dual sequential ionic crosslinking scheme to create interpenetrating networks (IPN) of alginate and cellulose with divalent and trivalent ions, respectively. The IPN alginate-cellulose beads demonstrate superior mechanical strength and controllable rigidity as well as enhanced resistance to harsh chemical environment as compared to alginate beads. Furthermore, their suitability for biomedical applications is also demonstrated by encapsulating microbial species to maximize their bioactivity and therapeutic agents for controlled release.
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References
Agarwal T, Narayana SNGH, Pal K, Pramanik K, Giri S, Banerjee I (2015) Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery. Int J Biol Macromol 75:409–417. doi:10.1016/j.ijbiomac.2014.12.052
Anseth KS, Bowman CN, Brannon-Peppas L (1996) Mechanical properties of hydrogels and their experimental determination. Biomaterials 17:1647–1657. doi:10.1016/0142-9612(96)87644-7
Bashan Y (1986) Alginate beads as synthetic inoculant carriers for slow release of bacteria that affect plant growth. Appl Environ Microbiol 51:1089–1098
Cha C, Kim SR, Jin Y-S, Kong H (2012) Tuning structural durability of yeast-encapsulating alginate gel beads with interpenetrating networks for sustained bioethanol production. Biotechnol Bioeng 109:63–73. doi:10.1002/bit.23258
Cha C et al (2014) Microfluidics-assisted fabrication of gelatin-silica core–shell microgels for injectable tissue constructs. Biomacromol 15:283–290. doi:10.1021/bm401533y
Chan ES et al (2011) Effects of starch filler on the physical properties of lyophilized calcium–alginate beads and the viability of encapsulated cells. Carbohydr Polym 83:225–232. doi:10.1016/j.carbpol.2010.07.044
Chitprasert P, Sudsai P, Rodklongtan A (2012) Aluminum carboxymethyl cellulose–rice bran microcapsules: Enhancing survival of Lactobacillus reuteri KUB-AC5. Carbohydr Polym 90:78–86. doi:10.1016/j.carbpol.2012.04.065
Chremos A, Douglas JF (2016) Influence of higher valent ions on flexible polyelectrolyte stiffness and counter-ion distribution. J Chem Phys 144:164904. doi:10.1063/1.4947221
Cormack BP, Valdivia RH, Falkow S (1996) FACS-optimized mutants of the green fluorescent protein (GFP). Gene 173:33–38. doi:10.1016/0378-1119(95)00685-0
Covarrubias SA, de Bashan LE, Moreno M, Bashan Y (2012) Alginate beads provide a beneficial physical barrier against native microorganisms in wastewater treated with immobilized bacteria and microalgae. Appl Microbiol Biotechnol 93:2669–2680. doi:10.1007/s00253-011-3585-8
Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67:217–223
Emregül E, Sungur S, Akbulut U (1996) Effect of chromium salts on invertase immobilization onto carboxymethylcellulose-gelatine carrier system. Biomaterials 17:1423–1427. doi:10.1016/0142-9612(96)87285-1
Fan L, Zhang J, Wang A (2013) In situ generation of sodium alginate/hydroxyapatite/halloysite nanotubes nanocomposite hydrogel beads as drug-controlled release matrices. J Mater Chem B 1:6261–6270. doi:10.1039/C3TB20971G
Fang A, Cathala B (2011) Smart swelling biopolymer microparticles by a microfluidic approach: synthesis, in situ encapsulation and controlled release. Colloids Surf B Biointerfaces 82:81–86. doi:10.1016/j.colsurfb.2010.08.020
Fu Y, Kao WJ (2009) Drug release kinetics and transport mechanisms from semi-interpenetrating networks of gelatin and poly(ethylene glycol) diacrylate. Pharm Res. doi:10.1007/s11095-009-9923-1
George M, Abraham TE (2006) Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan—a review. J Control Release 114:1–14. doi:10.1016/j.jconrel.2006.04.017
Gombotz WR, Wee SF (2012) Protein release from alginate matrices Adv Drug Deliver Rev 64(Supplement):194–205. doi:10.1016/j.addr.2012.09.007
Hari PR, Chandy T, Sharma CP (1996) Chitosan/calcium–alginate beads for oral delivery of insulin. J Appl Polym Sci 59:1795–1801
Hashmi SM, Dufresne ER (2009) Mechanical properties of individual microgel particles through the deswelling transition. Soft Matter 5:3682–3688. doi:10.1039/B906051K
Hoenich N (2006) Cellulose for medical applications: past, present, and future. BioRes 1:270–280
Jang J, Hong J, Cha C (2017) Effects of precursor composition and mode of crosslinking on mechanical properties of graphene oxide reinforced composite hydrogels. J Mech Behav Biomed Mater 69:282–293. doi:10.1016/j.jmbbm.2017.01.025
Jorfi M, Foster EJ (2015) Recent advances in nanocellulose for biomedical applications. J Appl Polym Sci. doi:10.1002/app.41719
Kil KC, Paik U (2015) Lithium salt of carboxymethyl cellulose as an aqueous binder for thick graphite electrode in lithium ion batteries. Macromol Res 23:719–725. doi:10.1007/s13233-015-3094-1
Kim MS, Park SJ, Gu BK, Kim C-H (2012) Ionically crosslinked alginate–carboxymethyl cellulose beads for the delivery of protein therapeutics. Appl Surf Sci 262:28–33. doi:10.1016/j.apsusc.2012.01.010
Kim S, Lee K, Cha C (2016) Refined control of thermoresponsive swelling/deswelling and drug release properties of poly(N-isopropylacrylamide) hydrogels using hydrophilic polymer crosslinkers. J Biomater Sci Polym Ed 27:1698–1711. doi:10.1080/09205063.2016.1230933
Ko H-U, John A, Mun S, Im J, Kim J (2015) Preparation and characterization of Cellulose-ZnO nanolayer film by blending method. Macromol Res 23:814–818. doi:10.1007/s13233-015-3111-4
Kulkarni AR, Soppimath KS, Aminabhavi TM, Rudzinski WE (2001) In-vitro release kinetics of cefadroxil-loaded sodium alginate interpenetrating network beads. Eur J Pharm Biopharm 51:127–133. doi:10.1016/S0939-6411(00)00150-8
Lee KY, Mooney DJ (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37:106–126. doi:10.1016/j.progpolymsci.2011.06.003
Lee TS et al (2011) BglBrick vectors and datasheets: a synthetic biology platform for gene expression. J Biol Eng 5:12. doi:10.1186/1754-1611-5-12
Lee JY, Kwak HW, Yun H, Kim YW, Lee KH (2016) Methyl cellulose nanofibrous mat for lipase immobilization via cross-linked enzyme aggregates. Macromol Res 24:218–225. doi:10.1007/s13233-016-4028-2
Lim F, Sun AM (1980) Microencapsulated islets as bioartificial endocrine pancreas Science 210:908–910. doi:10.1126/science.6776628
Lin DC, Dimitriadis EK, Horkay F (2007) Elasticity of rubber-like materials measured by AFM nanoindentation Express Polym Lett 1:576–584. doi:10.3144/expresspolymlett.2007.79
Mørch ÝA, Donati I, Strand BL (2006) Effect of Ca2+, Ba2+, and Sr2+ on alginate microbeads. Biomacromol 7:1471–1480. doi:10.1021/bm060010d
Ouwerx C, Velings N, Mestdagh MM, Axelos MAV (1998) Physico-chemical properties and rheology of alginate gel beads formed with various divalent cations Polym Gels. Networks 6:393–408. doi:10.1016/S0966-7822(98)00035-5
Pfister G, Bahadir M, Korte F (1986) Release characteristics of herbicides from Ca alginate gel formulations. J Control Release 3:229–233. doi:10.1016/0168-3659(86)90094-5
Ramos LA, Frollini E, Heinze T (2005) Carboxymethylation of cellulose in the new solvent dimethyl sulfoxide/tetrabutylammonium fluoride. Carbohydrate Polym 60:259–267. doi:10.1016/j.carbpol.2005.01.010
Rathore S, Desai PM, Liew CV, Chan LW, Heng PWS (2013) Microencapsulation of microbial cells. J Food Eng 116:369–381. doi:10.1016/j.jfoodeng.2012.12.022
Serra L, Doménech J, Peppas NA (2006) Drug transport mechanisms and release kinetics from molecularly designed poly(acrylic acid-g-ethylene glycol) hydrogels. Biomaterials 27:5440–5451. doi:10.1016/j.biomaterials.2006.06.011
Shen Y et al (2016) pH and redox dual stimuli-responsive injectable hydrogels based on carboxymethyl cellulose derivatives. Macromol Res 24:602–608. doi:10.1007/s13233-016-4077-6
Shi J, Alves NM, Mano JF (2008) Chitosan coated alginate beads containing poly(N-isopropylacrylamide) for dual-stimuli-responsive drug release. J Biomed Mater Res Part B: Appl Biomater 84B:595–603. doi:10.1002/jbm.b.30907
Sindhu KA, Prasanth R, Thakur VK (2014) Medical applications of cellulose and its derivatives: present and future. In: Nanocellulose Polymer Nanocomposites. John Wiley and Sons, Inc., pp 437–477. doi:10.1002/9781118872246.ch16
Siritientong T, Aramwit P (2015) Characteristics of carboxymethyl cellulose/sericin hydrogels and the influence of molecular weight of carboxymethyl cellulose. Macromol Res 23:861–866. doi:10.1007/s13233-015-3116-z
Smidsrød O, Skja˚k-Br˦k G (1990) Alginate as immobilization matrix for cells. Trends Biotechnol 8:71–78. doi:10.1016/0167-7799(90)90139-O
Sugiura S et al (2005) Size control of calcium alginate beads containing living cells using micro-nozzle array. Biomaterials 26:3327–3331. doi:10.1016/j.biomaterials.2004.08.029
Thu B, Bruheim P, Espevik T, Smidsrød O, Soon-Shiong P, Skjåk-Bræk G (1996a) Alginate polycation microcapsules: I. interaction between alginate and polycation. Biomaterials 17:1031–1040. doi:10.1016/0142-9612(96)84680-1
Thu B, Bruheim P, Espevik T, Smidsrød O, Soon-Shiong P, Skjåk-Bræk G (1996b) Alginate polycation microcapsules: II. some functional properties. Biomaterials 17:1069–1079. doi:10.1016/0142-9612(96)85907-2
Tønnesen HH, Karlsen J (2002) Alginate in drug delivery systems. Drug Dev Ind Pharm 28:621–630. doi:10.1081/DDC-120003853
Van Benschoten JE, Edzwald JK (1990) Chemical aspects of coagulation using aluminum salts—I. hydrolytic reactions of alum and polyaluminum chloride. Water Res 24:1519–1526. doi:10.1016/0043-1354(90)90086-L
Xiao C, Li H, Gao Y (2009) Preparation of fast pH-responsive ferric carboxymethylcellulose/poly(vinyl alcohol) double-network microparticles. Polym Int 58:112–115. doi:10.1002/pi.2502
Xiong G, Luo H, Zhang C, Zhu Y, Wan Y (2015) Enhanced biological behavior of bacterial cellulose scaffold by creation of macropores and surface immobilization of collagen. Macromol Res 23:734–740. doi:10.1007/s13233-015-3099-9
Yang XH, Zhu WL (2007) Viscosity properties of sodium carboxymethylcellulose solutions Cellulose 14:409–417. doi:10.1007/s10570-007-9137-9
Zhang L-M (2001) New water-soluble cellulosic polymers: a review. Macromol Mater Eng 286:267–275. doi:10.1002/1439-2054(20010501)286:5<267:AID-MAME267>3.0.CO;2-3
Zhang J, Wang Q, Wang A (2010) In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices. Acta Biomater 6:445–454. doi:10.1016/j.actbio.2009.07.001
Zhang K, Brendler E, Gebauer K, Gruner M, Fischer S (2011) Synthesis and characterization of low sulfoethylated cellulose Carbohydrate Polym 83:616–622. doi:10.1016/j.carbpol.2010.08.030
Acknowledgments
This study was supported by the 2017 Research Fund (1.170008.01 and 1.170050.01) of UNIST (Ulsan National Institute of Science and Technology) and Civil-Military Technology Cooperation Program (15-CM-SS) of Korea.
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Lee, K., Hong, J., Roh, H.J. et al. Dual ionic crosslinked interpenetrating network of alginate-cellulose beads with enhanced mechanical properties for biocompatible encapsulation. Cellulose 24, 4963–4979 (2017). https://doi.org/10.1007/s10570-017-1458-8
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DOI: https://doi.org/10.1007/s10570-017-1458-8