Abstract
Two series of novel hydrogels, based on 2-hydroxyethyl acrylate (HEA), itaconic acid (IA), and two poly(ethylene glycol) dimethacrylates (PEGDMA), of different ethylene glycol chain lengths, were prepared by free radical crosslinking copolymerization. The influence of different ethylene glycol chain lengths and concentration in P(HEA/IA/PEGDMA) hydrogels on biocompatibility, swelling and thermal properties was investigated. All samples in contact with blood showed a mean hemolysis value <1.0 % in the direct contact assay, and even <0.5 % in the indirect contact assay, for in vitro testing conditions. Swelling studies, conducted in a physiological pH and temperature range, showed pH sensitivity and relatively small changes of equilibrium swelling with temperature, which varied with PEGDMA molecular weight. The glass transition temperatures (T g) of P(HEA/IA/PEGDMA) networks were in the range 28.1–36.9 °C, respectively, and also dependent on copolymer composition. Due to good biocompatibility, favorable swelling, and thermal properties these hydrogels show good potential for biomedical uses.
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Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J (2000) Physicochemical foundations and structural design of hydrogels in medicine and biology. Annu Rev Biomed Eng 2:9–29
Kumar A, Srivastava A, Galaev IY, Mattiasson B (2007) Smart polymers: physical forms & bioengineering applications. Prog Polym Sci 32:1205–1237
Schmaljohann B (2006) Thermo- and pH-responsive polymers in drug delivery. Adv Drug Deliv Rev 58:1655–1670
Brahim S, Narinesingh D, Elie AG (2003) Synthesis and hydration properties of pH-sensitive p(HEMA)-based hydrogels containing 3-(trimethoxysilyl)propyl methacrylate. Biomacromolecules 4:497–503
Kou JH, Fleisher D, Amidon GL (1990) Modeling drug release from dynamically swelling poly(hydroxyethyl methacrylate-co-methacrylic acid) hydrogels. J Control Release 12:241–250
Albin G, Horbett TA, Miller SR, Ricker NL (1987) Theoretical and experimental studies of glucose sensitive membranes. J Control Release 6:267–291
Bajpai AK, Shukla SK, Bhanu S, Kankane S (2008) Responsive polymers in controlled drug delivery. Prog Polym Sci 33:1088–1118
Tomić SLj, Mićić MM, Filipović JM, Suljovrujić EH (2010) Synthesis, characterization and controlled release of cephalexin from smart poly(2-hydroxyethyl methacrylate/poly(alkylene glycol)(meth) acrylates hydrogels. Chem Eng J 160:801–809
Dobić SN, Filipović JM, Tomić SLj (2012) Synthesis and characterization of poly(2-hydroxyethyl methacrylate/itaconic acid/poly(ethylene glycol) dimethacrylate) hydrogels. Chem Eng J 179:372–380
Kakwere H, Perrier S (2011) Design of complex polymeric architectures and nanostructured materials/hybrids by living radical polymerization of hydroxylated monomers. Polym Chem 2:270–288
Montheard JP, Chatzopoulos M, Chappard DJ (1992) 2-hydroxyethyl methacrylate (HEMA); chemical properties and applications in biomedical fields. J Macromol Sci Macromol Rev 32:1–34
Mark HF (2007) Encyclopedia of polymer science and technology. Wiley, New York
Tomić SLj, Mićić MM, Filipović JM, Suljovrujić EH (2007) Swelling and drug release behavior of poly(2-hydroxyethyl methacrylate/itaconic acid) copolymeric hydrogels obtained by gamma irradiation. Radiat Phys Chem 76:801–810
Inam R, Caykara T, Ozyurek C (2001) Polarographic determination of uranyl ion adsorption on poly-(2-hydroxyethyl methacrylate/itaconic acid) hydrogels. Sep Sci Technol 36:1451–1461
Ozyurek C, Caykara T, Inam R (2003) Enhancement of uranyl ion uptake by the prestructuring of poly(2-hydroxyethyl methacrylate itaconic acid) hydrogels in the presence of lead and cadmium ions/polarographic determination. J Appl Polym Sci 90:2385–2390
Hamdy SM, El-Sigeny S, Abou Taleb MF (2008) Immobilization of urease on (HEMA/IA) hydrogel prepared by gamma radiation. J Macromol Sci A 45:982–989
Tomić SLj, Suljovrujić EH, Filipović JM (2006) Biocompatible and bioadhesive hydrogels based on 2-hydroxyethyl methacrylate, monofunctional poly(alkylene glycol)s and itaconic acid. Polym Bull 57:691–702
Lin CC, Anseth KS (2009) PEG hydrogels for the controlled release of biomolecules in regenerative medicine. Pharm Res 26:631–643
Drury JL, Mooney DJ (2003) Hydrogels for tissue engineering: scaffold design variables and applications. Biomaterials 24:4337–4351
Mellott MB, Searcy K, Pishko MV (2001) Release of protein from highly crosslinked hydrogels poly(ethylene glycol) diacrylate fabricated by UV polymerization. Biomaterials 22:929–941
Gallego Ferrer G, Salmerón Sánchez M, Gómez Ribelles JL, Romero Colomer FJ, Monleón Pradas M (2007) Nanodomains in a hydroplylic–hydrophobic IPN based on poly(2-hydroxyethyl acrylate) and poly(ethyl acrylate). Eur Polym J 43:3136–3145
Jeon SI, Lee JH, Andrade JD, De Gennes PG (1991) Protein–surface interactions in the presence of polyethylene oxide. J Colloid Interf Sci 142:149–158
Nagaoka S, Mori Y, Takiuchi H, Yokota K, Tanzawa H, Nichiumi S (1984) Interaction between blood components and hydrogels with poly(oxyethylene) chains. Plenum Press, New York
Al-Nasassrah MA, Podczeck F, Newton JM (1998) The effect of an increase in chain length on the mechanical properties of polyethylene glycols. Eur J Pharm Biopharm 46:31–38
Gunn JW, Turner SD, Mann BK (2005) Adhesive and mechanical properties of hydrogels influence neurite extension. J Biomed Mater Res A 72:91–97
Padmavathi NC, Chatterji PR (1996) Structural characterization and swelling behavior of poly(ethylene glycol) diacrylate hydrogels. Macromolecules 29:1976–1979
Peyton SR, Raub CB, Keschrumrus VP, Putnam AJ (2006) The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells. Biomaterials 27:4881–4893
Nemir S, Hayenga HN, West JL (2010) PEGDA hydrogels with patterned elasticity: novel tools for the study of cell response to substrate rigidity. Biotechnol Bioeng 105:636–644
Tomić SLj, Mićić MM, Dobić SN, Filipović JM, Suljovrujić EH (2010) Smart Poly(2-hydroxyethyl methacrylate/itaconic acid) hydrogels for biomedical application. Radiat Phys Chem 79:643–649
Tomić SLj, Jovašević JS, Filipović JM, Dobić SN (2010) 2nd Conference Innovation in Drug Delivery, Aix-en-Provence, France, Programme and Abstracts, p 154
Pertruccioli M, Pulchi V, Federici F (1999) Itaconic acid production by Aspergillus terreus on raw starchy materials. Lett Appl Microbial 28:309–312
Pal K, Banthia AK, Majumdar DK (2006) Starch based hydrogel with potential biomedical application as artificial skin. Afr J Biomed Res 9:23–29
ISO document (1992) 10, 993–5: Part 4
(2003) Guide to the preparation, use and quality assurance of blood components, 9th edn. Council of Europe Publishing Strasbourg, France
(1986) FDA summary basis of approval for red blood cells frozen and red blood cells deglycerolized (Reference number 86-0335). US License Number 635-10. Applicant-Department of the Navy, Navy Hospital, Bethesda
Han V, Serrano K, Devine DV (2010) A comparative study of common techniques used to measure haemolysis in stored red cell concentrates. Vox Sang 98:116–123
Bell CL, Peppas NA (1995) Measurement of the swelling force in ionic polymer networks. III. Swelling force of interpolymer complexes. J Control Release 37:277–280
Peppas NA (1985) Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv 60:110–111
Park JB, Lakes RS (2007) Tissue Response to Implants. In: Biomaterials. Springer, Berlin, pp 266–288
Pizzoferrato A, Vespucci A, Ciapetti G, Stea S (1985) Biocompatibility testing of prosthetic implant materials by cell culture. Biomaterials 6:346–351
Williams D (1991) Objectivity in the evaluation of biological safety of medical devices and biomaterials. Med Device Technol 2:44–48
Bruck SD (1980) Problems and artifacts in the evaluation of polymeric materials for medical uses. Biomaterials 1:103–107
Williams DF (1981) Biomaterials and Biocompatibility. CRC Press, Boca Raton
Sharp MK, Mohammad SF (1998) The scaling of haemolysis in needles and catheters. Ann Biomed Eng 26:788–797
Tomić SLj, Dimitrijević SI, Marinković AD, Najman S, Filipović JM (2009) Synthesis and characterization of poly (2-hydroxyethyl methacrylate/itaconic acid) copolymeric hydrogels. Polym Bull 63:837–851
Mishra A, Chaudhary N (2010) Study of povidone iodine loaded hydrogels as wound dressing material. Trends Biomater Artif Organs 23:122–128
Caykara T, Dogmus M, Kantoglu OJ (2004) Network structure and swelling-shrinking behaviors of pH-sensitive poly(acrylamide-co-itaconic acid) hydrogels. Polym Sci Part B Pol Phys 42:2586–2594
Canal T, Peppas NA (1989) Correlation between mesh size and equilibrium degree of swelling of polymeric networks. J Biomed Mater Res 23:1183–1193
Gudeman LF, Peppas NA (1995) pH-Sensitive membranes from poly (vinyl alcohol)/poly (acrylic acid) interpenetrating networks. J Membr Sci 107:239–248
Aran B, Sankir M, Vargun E, Sankir ND, Usanmaz A (2010) Tailoring the swelling and glass-transition temperature of acrylonitrile/hydroxyethyl acrylate copolymers. J Appl Polym Sci 116:628–635
Spanoudaki A, Fragiadakis D, Vartzelinikaki K, Pissis P, Rodriguez Hernandez JC, Monleon Pradas M (2006) Nanostructured and nanocomposite hydrogels for biomedical applications. In: Blitz JP, Gun’ko VM (eds) Surface chemistry in biomedical and environmental science. Springer, Berlin, pp 229–240
Gomez Ribelles JL, Monleon Pradas M, Gallego Ferrer G, Peidro Torres N, Perez Gimenez V, Pissis P, Kyritsis AJ (1999) Poly(methyl acrylate)/poly(hydroxyethyl acrylate) sequential interpenetrating polymer networks. Miscibility and water sorption behavior. Poly Sci Part B Pol Phys 37:1587–1599
Russell GA, Hiltner PA, Gregonis DE, Visser AC, Andrade JD (1980) Thermal and dynamic mechanical relaxation behavior of stereoregular poly(2-hydroxyethyl methacrylate). J Polym Sci Part B Pol Phys 18:1271–1283
Fernandez-Garcia M, Torrado MF, Marinez G, Sanchez-Chaves M, Madruga EL (2000) Free radical copolymerization of 2-hydroxyethyl methacrylate with butyl methacrylate. Determination of monomer reactivity ratios and glass transition temperatures. Polymer 41:8001–8008
Ortiz C, Vasquez B, SanRoman J (1998) Synthesis, characterization and properties of polyacrylic systems derived from vitamin E. Polymer 39:4107–4114
Caykara T, Ozyurek C, Kantoglu O (2007) Investigation of thermal behavior of poly(2-hydroxyethyl methacrylate-co-itaconic acid) networks. J Appl Polym Sci 103:1602–1607
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This work has been supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grants No. 172026 and 172062).
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Tomić, S.L., Jovašević, J.S. & Filipović, J.M. Hemocompatibility, swelling and thermal properties of hydrogels based on 2-hydroxyethyl acrylate, itaconic acid and poly(ethylene glycol) dimethacrylate. Polym. Bull. 70, 2895–2909 (2013). https://doi.org/10.1007/s00289-013-0995-z
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DOI: https://doi.org/10.1007/s00289-013-0995-z