The existence of correlation and functional relationships between reaction conditions (concentrations of crosslinker, monomer and initiator, and neutralization degree of monomer), primary structural parameters (crosslinking density of network, average molar mass between crosslinks, and distance between macromolecular chains), and macroscopic properties (equilibrium swelling degree and xerogel density) of the synthesized xerogels which are important for application in tissue engineering is investigated. The structurally different xerogels samples of poly(acrylic acid), poly(methacrylic acid), and poly(acrylic acid-g-gelatin) were synthesized by applying different methods of polymerization: crosslinking polymerization, crosslinking polymerization in high concentrated aqueous solution, and crosslinking graft polymerization. The values of primary structural parameters and macroscopic properties were determined for the synthesized xerogels samples. For all of the investigated methods of polymerization, an existence of empirical power function of the dependence of primary structural parameters and macroscopic properties on the reaction conditions was established. The scaling laws between primary structural parameters and macroscopic properties on average molar mass between crosslinks were established. It is shown that scaling exponent is independent from the type of monomer and other reaction conditions within the same polymerization method. The physicochemical model that could be used for xerogel synthesis with predetermined macroscopic properties was suggested. 1. Application of Hydrogels in Tissue Engineering Every year, millions of patients suffer the loss or failure of an organ or tissue as a result of accidents or disease. The field of tissue engineering has developed to meet the tremendous need for organs and tissues [1–3]. Hydrogels are commonly defined as three-dimensional networks of hydrophilic polymers, capable of absorbing significant amounts of water (from 20？g/g up to 2000？g/g of their dry mass) without dissolving or losing their structural integrity [4, 5]. They are also called smart, intelligent, stimuli-responsive, or environmental sensitive materials when a rather sharp change can be induced by changes in the environmental conditions, for example, small changes in temperature. Stimuli-responsive hydrogels are described as smart or intelligent when their sol-gel transition occurs at conditions that can be induced in a living body [6]. Due to their characteristic properties (high swellability in water, hydrophilicity, biocompatibility, and
References
[1]
J. J. Grodzinski, “Polymeric gels and hydrogels for biomedical and pharmaceutical applications,” Polymers for Advanced Technologies, vol. 21, no. 1, pp. 27–47, 2010.
[2]
R. Langer and D. A. Tirrell, “Designing materials for biology and medicine,” Nature, vol. 428, no. 6982, pp. 487–492, 2004.
[3]
E. S. Place, N. D. Evans, and M. M. Stevens, “Complexity in biomaterials for tissue engineering,” Nature Materials, vol. 8, no. 6, pp. 457–470, 2009.
[4]
N. A. Peppas and A. G. Mikos, “Preparation methods and structure of hydrogels,” in Hydrogels in Medicine and Pharmacy, N. A. Peppas, Ed., pp. 2–23, CRC Press, Boca Raton, Fla, USA, 1986.
[5]
K. Park, W. C. W. Shalaby, and H. Park, “Hydrogels, definition, hydrogel as a biomaterial, biodegradable hydrogels, biodegradation,” in Biodegradable Hydrogels for Drug Delivery, K. Park, W. C. W. Shalaby, and H. Park, Eds., pp. 1–12, Technomic, Lancaster, UK, 1993.
[6]
S. Chaterji, I. K. Kwon, and K. Park, “Smart polymeric gels: redefining the limits of biomedical devices,” Progress in Polymer Science, vol. 32, no. 8-9, pp. 1083–1122, 2007.
[7]
A. Kikuchi and T. Okano, “Pulsatile drug release control using hydrogels,” Advanced Drug Delivery Reviews, vol. 54, no. 1, pp. 53–77, 2002.
[8]
S. H. Hu, T. Y. Liu, D. M. Liu, and S. Y. Chen, “Controlled pulsatile drug release from a ferrogel by a high-frequency magnetic field,” Macromolecules, vol. 40, no. 19, pp. 6786–6788, 2007.
[9]
D. S. Kohane and R. Langer, “Polymeric biomaterials in tissue engineering,” Pediatric Research, vol. 63, no. 5, pp. 487–491, 2008.
[10]
J. F. Mano, “Stimuli-responsive polymeric systems for biomedical applications,” Advanced Engineering Materials, vol. 10, no. 6, pp. 515–527, 2008.
[11]
M. Yamato, C. Konno, M. Utsumi, A. Kikuchi, and T. Okano, “Thermally responsive polymer-grafted surfaces facilitate patterned cell seeding and co-culture,” Biomaterials, vol. 23, no. 2, pp. 561–567, 2002.
[12]
Y. Yeo and D. S. Kohane, “Polymers in the prevention of peritoneal adhesions,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 68, no. 1, pp. 57–66, 2008.
[13]
N. E. Fedorovich, J. Alblas, J. R. de Wijn, W. E. Hennink, A. B.J. Verbout, and W. J.A. Dhert, “Hydrogels as extracellular matrices for skeletal tissue engineering: state-of-the-art and novel application in organ printing,” Tissue Engineering, vol. 13, no. 8, pp. 1905–1925, 2007.
[14]
S. M？ller, J. Weisser, S. Bischoff, and M. Schnabelrauch, “Dextran and hyaluronan methacrylate based hydrogels as matrices for soft tissue reconstruction,” Biomolecular Engineering, vol. 24, no. 5, pp. 496–504, 2007.
[15]
E. Ho, A. Lowman, and M. Marcolongo, “Synthesis and characterization of an injectable hydrogel with tunable mechanical properties for soft tissue repair,” Biomacromolecules, vol. 7, no. 11, pp. 3223–3228, 2006.
[16]
W. Lee, D. Choi, Y. Lee, D. N. Kim, J. Park, and W. G. Koh, “Preparation of micropatterned hydrogel substrate via surface graft polymerization combined with photolithography for biosensor application,” Sensors and Actuators, B, vol. 129, no. 2, pp. 841–849, 2008.
[17]
J. Hoffmann, M. Plotner, D. Kucling, and W.-J. Fischer, “Photopatterning of thermally sensitive hydrogel useful for micro actuators,” Sens Actuators, vol. 77, pp. 139–144, 1999.
[18]
J. D. Kretlow, L. Klouda, and A. G. Mikos, “Injectable matrices and scaffolds for drug delivery in tissue engineering,” Advanced Drug Delivery Reviews, vol. 59, no. 4-5, pp. 263–273, 2007.
[19]
Z. M. O. Rzaev, S. Din？er, and E. Pi？kin, “Functional copolymers of N-isopropylacrylamide for bioengineering applications,” Progress in Polymer Science, vol. 32, no. 5, pp. 534–595, 2007.
[20]
J. L. Drury and D. J. Mooney, “Hydrogels for tissue engineering: scaffold design variables and applications,” Biomaterials, vol. 24, no. 24, pp. 4337–4351, 2003.
[21]
S. Varghese and J. H. Elisseeff, “Hydrogels for musculoskeletal tissue engineering,” Advances in Polymer Science, vol. 203, no. 1, pp. 95–144, 2006.
[22]
K. Tuzlakoglu, C. M. Alves, J. F. Mano, and R. L. Reis, “Production and characterization of chitosan fibers and 3-D fiber mesh scaffolds for tissue engineering applications,” Macromolecular Bioscience, vol. 4, no. 8, pp. 811–819, 2004.
[23]
T. Guo, J. Zhao, J. Chang et al., “Porous chitosan-gelatin scaffold containing plasmid DNA encoding transforming growth factor-β1 for chondrocytes proliferation,” Biomaterials, vol. 27, no. 7, pp. 1095–1103, 2006.
[24]
Y. Liu and M. B. Chan-Park, “Hydrogel based on interpenetrating polymer networks of dextran and gelatin for vascular tissue engineering,” Biomaterials, vol. 30, no. 2, pp. 196–207, 2009.
[25]
S. Young, M. Wong, Y. Tabata, and A. G. Mikos, “Gelatin as a delivery vehicle for the controlled release of bioactive molecules,” Journal of Controlled Release, vol. 109, no. 1–3, pp. 256–274, 2005.
[26]
F. M. Chen, Y. M. Zhao, H. H. Sun et al., “Novel glycidyl methacrylated dextran (Dex-GMA)/gelatin hydrogel scaffolds containing microspheres loaded with bone morphogenetic proteins: formulation and characteristics,” Journal of Controlled Release, vol. 118, no. 1, pp. 65–77, 2007.
[27]
F. M. Chen, Y. M. Zhao, R. Zhang et al., “Periodontal regeneration using novel glycidyl methacrylated dextran (Dex-GMA)/gelatin scaffolds containing microspheres loaded with bone morphogenetic proteins,” Journal of Controlled Release, vol. 121, no. 1-2, pp. 81–90, 2007.
[28]
J. D. Kosmala, D. B. Henthorn, and L. Brannon-Peppas, “Preparation of interpenetrating networks of gelatin and dextran as degradable biomaterials,” Biomaterials, vol. 21, no. 20, pp. 2019–2023, 2000.
[29]
Y. Lu, D. Wang, T. Li et al., “Poly(vinyl alcohol)/poly(acrylic acid) hydrogel coatings for improving electrode-neural tissue interface,” Biomaterials, vol. 30, no. 25, pp. 4143–4151, 2009.
[30]
K. Y. Lee and D. J. Mooney, “Hydrogels for tissue engineering,” Chemical Reviews, vol. 101, no. 7, pp. 1869–1879, 2001.
[31]
Y. Teramura, Y. Kaneda, and H. Iwata, “Islet-encapsulation in ultra-thin layer-by-layer membranes of poly(vinyl alcohol) anchored to poly(ethylene glycol)-lipids in the cell membrane,” Biomaterials, vol. 28, no. 32, pp. 4818–4825, 2007.
[32]
D. Mawad, P. J. Martens, R. A. Odell, and L. A. Poole-Warren, “The effect of redox polymerisation on degradation and cell responses to poly (vinyl alcohol) hydrogels,” Biomaterials, vol. 28, no. 6, pp. 947–955, 2007.
[33]
J. Choi, H. Bodugoz-Senturk, H. J. Kung, A. S. Malhi, and O. K. Muratoglu, “Effects of solvent dehydration on creep resistance of poly(vinyl alcohol) hydrogel,” Biomaterials, vol. 28, no. 5, pp. 772–780, 2007.
[34]
Y. M. Yue, K. Xu, X. G. Liu, Q. Chen, X. Sheng, and P. X. Wang, “Preparation and characterization of interpenetration polymer network films based on poly(vinyl alcohol) and poly(acrylic acid) for drug delivery,” Journal of Applied Polymer Science, vol. 108, no. 6, pp. 3836–3842, 2008.
[35]
E. De Giglio, S. Cometa, N. Cioffi, L. Torsi, and L. Sabbatini, “Analytical investigations of poly(acrylic acid) coatings electrodeposited on titanium-based implants: a versatile approach to biocompatibility enhancement,” Analytical and Bioanalytical Chemistry, vol. 389, no. 7-8, pp. 2055–2063, 2007.
[36]
J. Dai, Z. Bao, L. Sun, S. U. Hong, G. L. Baker, and M. L. Bruening, “High-capacity binding of proteins by poly(acrylic acid) brushes and their derivatives,” Langmuir, vol. 22, no. 9, pp. 4274–4281, 2006.
[37]
J. A. Hubbell, “Bioactive biomaterials,” Current Opinion in Biotechnology, vol. 10, no. 2, pp. 123–129, 1999.
[38]
J. A. Rowley, G. Madlambayan, and D. J. Mooney, “Alginate hydrogels as synthetic extracellular matrix materials,” Biomaterials, vol. 20, no. 1, pp. 45–53, 1999.
[39]
D. L. Hern and J. A. Hubbell, “Incorporation of adhesion peptides into nonadhesive hydrogels useful for tissue resurfacing,” Journal of Biomedical Materials Research, vol. 39, no. 2, pp. 266–276, 1998.
[40]
B. K. Mann, R. H. Schmedlen, and J. L. West, “Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells,” Biomaterials, vol. 22, no. 5, pp. 439–444, 2001.
[41]
Y. Suzuki, M. Tanihara, K. Suzuki, A. Saitou, W. Sufan, and Y. Nishimura, “Alginate hydrogel linked with syntheticoligiopeptide derived from BMP-2 allows ectopic osteoinduction in vivo,” Journal of Biomedical Materials Research, vol. 50, pp. 405–409, 2000.
[42]
J. Elisseeff, W. McIntosh, K. Fu, T. Blunk, and R. Langer, “Controlled-release of IGF-I and TGF-β1 in a photopolymerizing hydrogel for cartilage tissue engineering,” Journal of Orthopaedic Research, vol. 19, no. 6, pp. 1098–1104, 2001.
[43]
A. E. Bent, J. Foote, S. Siegel, G. Faerber, R. Chao, and E. A. Gormley, “Collagen implant for treating stress urinary incontinence in women with urethral hypermobility,” Journal of Urology, vol. 166, no. 4, pp. 1354–1357, 2001.
[44]
C. R. Nuttelman, D. J. Mortisen, S. M. Henry, and K. S. Anseth, “Attachment of fibronectin to poly(vinyl alcohol) hydrogels promotes NIH3T3 cell adhesion, proliferation, and migration,” Journal of Biomedical Materials Research, vol. 57, no. 2, pp. 217–223, 2001.
[45]
R. C. Thomson, M. C. Wake, M. J. Yaszemski, and A. G. Mikos, “Biodegradable polymer scaffolds to regenerate organs,” Advances in Polymer Science, vol. 122, pp. 245–274, 1995.
[46]
M. Dimitrov, N. Lambov, S. Shenkov, V. Dosseva, and V. Y. Baranovski, “Hydrogels based on the chemically crosslinked polyacrylic acid: biopharmaceutical characterization,” Acta Pharmaceutica, vol. 53, no. 1, pp. 25–31, 2003.
[47]
M. Changez, V. Koul, B. Krishna, A. K. Dinda, and V. Choudhary, “Studies on biodegradation and release of gentamicin sulphate from interpenetrating network hydrogels based on poly(acrylic acid) and gelatin: in vitro and in vivo,” Biomaterials, vol. 25, no. 1, pp. 139–146, 2004.
[48]
J. S. Ahn, H. K. Choi, M. K. Chun et al., “Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro,” Biomaterials, vol. 23, no. 6, pp. 1411–1416, 2002.
[49]
Z. Juranic, L. Stevovic, B. Drakulic, T. Stanojkovic, S. Radulovic, and I. Juranic, “Substituted (E)-(benzoil) acrylic acid suppressed survival of neoplastic HeLacels,” Journal of the Serbian Chemical Society, vol. 64, no. 9, pp. 505–512, 1999.
[50]
B. Adnadjevic, J. Jovanovic, and B. Drakulic, “Isothermal kinetics of (E)-4-(4-metoxyphenyl)-4-oxo-2-butenoic acid release from poly(acrylic acid) hydrogel,” Thermochimica Acta, vol. 466, no. 1-2, pp. 38–48, 2007.
[51]
B. Adnadjevic and J. Jovanovic, “A comparative kinetics study of isothermal drug release from poly(acrylic acid) and poly(acrylic-co-methacrylic acid) hydrogels,” Colloids and Surfaces B, vol. 69, no. 1, pp. 31–42, 2009.
[52]
K. M. Gupta, S. R. Barnes, R. A. Tangaro et al., “Temperature and pH sensitive hydrogels: an approach towards smart semen-triggered vaginal microbicidal vehicles,” Journal of Pharmaceutical Sciences, vol. 96, no. 3, pp. 670–681, 2007.
[53]
M. Dittgen, M. Durrani, and K. Lehmann, “Acrylic polymers—a review of pharmaceutical applications,” S.T.P. Pharma Sciences, vol. 7, no. 6, pp. 403–437, 1997.
[54]
A. Besheer, K. M. Wood, N. A. Peppas, and K. M？der, “Loading and mobility of spin-labeled insulin in physiologically responsive complexation hydrogels intended for oral administration,” Journal of Controlled Release, vol. 111, no. 1-2, pp. 73–80, 2006.
[55]
D. F. Williams, “On the mechanisms of biocompatibility,” Biomaterials, vol. 29, no. 20, pp. 2941–2953, 2008.
[56]
J. Kope？ek and J. Yang, “Hydrogels as smart biomaterials,” Polymer International, vol. 56, no. 9, pp. 1078–1098, 2007.
[57]
A. S. Hoffman, “Hydrogels for biomedical applications,” Advanced Drug Delivery Reviews, vol. 54, no. 1, pp. 3–12, 2002.
[58]
F. Lim, “Microencapsulation of living cells and tissues—theory and practice,” in Biomedical Applications of Microencapsulation, pp. 137–154, CRC Press, Boca Raton, Fla, USA, 1984.
[59]
F. Brandl, F. Sommer, and A. Goepferich, “Rational design of hydrogels for tissue engineering: impact of physical factors on cell behavior,” Biomaterials, vol. 28, no. 2, pp. 134–146, 2007.
[60]
M. S. Shoichet, “Polymer scaffolds for biomaterials applications,” Macromolecules, vol. 43, no. 2, pp. 581–591, 2010.
[61]
P. J. Flory and J. Rehner, “Statistical mechanics of cross-linked polymer networks I. Rubberlike elasticity,” The Journal of Chemical Physics, vol. 11, no. 11, pp. 512–520, 1943.
[62]
J. Brandrup and E. H. Immergut, Polymer Handbook, John Wiley & Sons, New York, NY, USA, 2nd edition, 1975.
[63]
H. R. Allcock and W. L. Frederick, Contemporary Polymer Chemistry, Prentice Hall, Englewood Cliffs, NJ, USA, 1981.
[64]
H. Tobita and A. E. Hamielec, “Control of network structure in free-radical crosslinking copolymerization,” Polymer, vol. 33, no. 17, pp. 3647–3657, 1992.
[65]
K. Dusek, “Network formation involving polyfunctional polymer chains,” in Polymer Networks: Principles of Their Formation Structure and Properties, R. F. T. Stepto, Ed., pp. 64–92, Blackie Academic and Professional, London, UK, 1998.
[66]
J. E. Elliott and C. N. Bowman, “Kinetics of primary cyclization reactions in cross-linked polymers: an analytical and numerical approach to heterogeneity in network formation,” Macromolecules, vol. 32, no. 25, pp. 8621–8628, 1999.
[67]
B. Adnadjevic and J. Jovanovic, “Novel approach in investigation of the poly(acrylic acid) hydrogel swelling kinetics in water,” Journal of Applied Polymer Science, vol. 107, no. 6, pp. 3579–3587, 2008.
[68]
L. Bromberg, A. Y. Grosberg, E. S. Matsuo, Y. Suzuki, and T. Tanaka, “Dependency of swelling on the length of subchain in poly(N,N-dimethylacrylamide)-based gels,” Journal of Chemical Physics, vol. 106, no. 7, pp. 2906–2910, 1997.
[69]
A. Pastoriza, I. E. Pacios, and I. F. Piérola, “Kinetics of solvent responsiveness in poly(N,N-dimethylacrylamide) hydrogels of different morphology,” Polymer International, vol. 54, no. 8, pp. 1205–1211, 2005.
[70]
Z. Chen, C. Cohen, and F. A. Escobedo, “Monte Carlo simulation of the effect of entanglements on the swelling and deformation behavior of end-linked polymeric networks,” Macromolecules, vol. 35, no. 8, pp. 3296–3305, 2002.
[71]
P. J. Flory, Principles of Polymeric Chemistry, Cornell University Press, Ithaca, NY, USA, 1953.
[72]
J. Chen and Y. Zhao, “Relationship between water absorbency and reaction conditions in aqueous solution polymerization of polyacrylate superabsorbents,” Journal of Applied Polymer Science, vol. 75, no. 6, pp. 808–814, 2000.
[73]
A. Pourjavadi, A. M. Harzandy, and H. Hosseinzadeh, “Synthesis of novel polysaccharide—based superabsorbent hydtogel via graft coplymerization of acrylic acid onto kappa- carragenan in air,” European Polymer Journal, vol. 40, pp. 1363–1370, 2004.
[74]
I. E. Pacios, M. J. Molina, M. Rosa Gonez-Anton, and I. F. Pierola, “Correlation of swelling and crosslinking density with the composition of the reactiong mixture employed in radical crosslinking copolymerization,” Journal of Applied Polymer Science, vol. 103, pp. 263–269, 2007.
[75]
S. P. Obukhov, M. Rubinstein, and R. H. Colby, “Network modulus and superelasticity,” Macromolecules, vol. 27, no. 12, pp. 3191–3198, 1994.
[76]
H. Furukawa, “Effect of varying preparing-concentration on the equilibrium swelling of polyacrylamide gels,” Journal of Molecular Structure, vol. 554, no. 1, pp. 11–19, 2000.
[77]
P. G. De Gennes, Scaling Concepts in Polymer Ohysics, Cornell University Press, Ithaca, NY, USA, 1979.
