Preparation and investigation of hydrolyzed polyacrylonitrile as a preliminary biomedical hydrogel
- Ji Hoon Park†1,
- Guo Zhe Tai†1,
- Bo Keun Lee1,
- Seung Hun Park1,
- Ja Yong Jang1,
- Jung Soo Lee1, 2,
- Jae Ho Kim1,
- Kwideok Park3,
- Ju Woong Jang2 and
- Moon Suk Kim1Email author
© Park et al. 2016
Received: 1 September 2015
Accepted: 19 October 2015
Published: 26 October 2015
Hydrolyzed polyacrylonitrile (HPAN) has attracted much attention as a hydrogel for a broad range of biomedical applications. Therefore, in this study, we prepared HPAN derivatives with controllable compositions by the radical polymerization of acrylonitrile (AN), methacrylic acid (MAA) and N-isopropylacrylamide (NIPAM) monomers.
The prepared poly(AN-co-MAA-co-NIPAM) copolymers had different ratios of AN, MAA, and NIPAM and molecular weights ranging from 2000 to 50,000. The copolymers were prepared as films to examine their properties. The prepared copolymer films showed different solubilities, contact angles, and swelling ratios. The properties of the copolymer films were affected by the hydrophobic PAN segments and the hydrophilic PMAA or PNIPAM segments.
Thus, we conclude that introducing PMAA and PNIPAM segments with different ratios and lengths into PAN segments could represent a method of controlling the hydrogel properties of copolymers.
Hydrogels have been developed extensively for a broad range of biomedical applications [1, 2]. Most types of hydrogels can absorb large quantities of water relative to their initial weight because of their intrinsic hydrophilicity. Because of this propensity to retain large amounts of water, hydrogels can be used in biomedical applications in dehydrated and/or hydrated form. Hydrogels have been applied extensively as smart polymers for drug carriers, contact lens materials, and orthopedic implants [3–7]. In vivo, hydrogels expand to form swelled shapes by absorbing body-derived fluids [8–11].
Many hydrogels have been developed using various polymers. Among them, partial hydrolyzed polyacrylonitrile (HPAN) is produced through a chemical reaction of polyacrylonitrile (PAN) with sodium hydroxide [12–14]. The reaction produces a water-soluble HPAN block copolymer consisting of hydrophobic nitrile functional groups and hydrophilic poly(acrylic acid), partially neutralized poly(acrylic acid), and poly(acrylamide) [15–18].
HPAN mainly expands in water and/or in body-derived fluids to form swollen hydrogels that are highly biocompatible and biodurable and cause minimal inflammation following implantation. Uniquely, HPAN shows elasticity and tensile strength that are very similar to those of body tissues, such as cartilage and the nucleus pulposus of the intervertebral disc [19–21]. Thus, HPAN has been developed extensively for minimally invasive spine surgery .
Although HPAN has a significant advantage in biomedical applications, control over the hydrophilic and hydrophobic segments is limited by the hetero-chemical reaction of PAN with sodium hydroxide and/or amine. Thus, developing a simple preparation method for HPAN copolymers with controllable composition has been the subject of practical development efforts.
HPAN derivatives can be easily prepared using acrylonitrile (AN), methacrylic acid (MAA) and N-isopropylacrylamide (NIPAM) monomers, which are cheap and easy to polymerize. The prepared poly(AN–co-MAA-co-NIPAM) copolymer derivatives have the ability to absorb higher water and form hydrogel, which is an essential criterion for a hydrogel suitable for biomedical applications.
To the best of our knowledge, few previous studies have addressed the preparation of HPAN derivatives with controllable compositions. Thus, in this work, we prepared HPAN derivatives with controllable compositions of AN, MAA and NIPAM by radical polymerization. The solution and swelling properties of the copolymer were also examined for hydrogel application.
Acrylonitrile (AN), methacrylic acid (MAA), and N-isopropylacrylamide (NIPAM) were purchased from Aldrich (MO, USA) and distilled over CaH2 under reduced pressure. Azobisisobutyronitrile (AIBN) was recrystallized in methanol. THF was purchased from Burdick & Jackson (MI, USA). The HPLC-grade n-hexane and ethyl ether were purchased from Samchun (Pyeongtaek, Korea) and used as received.
Synthesis of poly(AN-co-MAA-co-NIPAM)
Preparation and swelling ratios of poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM) copolymers
Molar ratio (%) (AN-MAA-NIPAM)
Molar ratio (%) (AN-MAA-NIPAM)a
Swelling ratio (%)
Synthesis of poly(AN-co-MAA) and poly(AN-co-NIPAM)
Poly(AN-co-MAA) with an AN/MAA ratio of 50/50 and poly(AN-co-NIPAM) with an AN/NIPAM ratio of 50/50 were prepared using same copolymerization method as described in the previous section.
Determination of solution properties
250 mg of the poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM) copolymers were introduced into 5-mL vials. Two milliliter of distilled water (pH 7), a solution of pH 3, and a solution of pH 10 (Adjusted to the desire pH with 1 N HCl and NaOH) were added to the vials and incubated for 1 h and observed. The solubility of poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM) copolymers in DW was determined at 37 °C.
Preparation of copolymer films
Poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM) films were prepared using solvent casting. One milligram of copolymers was solubilized in 1 mL of THF. The solution was casted on polyethylene film and allowed to dry slowly at 10 °C for 2 d. Next, the casted films were dried in a vacuum oven at room temperature for 4 days, resulting in smooth and non-porous films. The copolymer films were cut into discs with 6 mm diameters and 200 μm thicknesses.
Contact angle measurement of copolymer films
The water contact angle was measured using the sessile drop method at room temperature with an optical bench-type contact angle goniometer (Phoenix 150, SEO, Suwon, Korea). One drop of purified water (5 μL) was deposited onto the prepared film surface by means of a microsyringe. The water contact angle was measured within 5 s.
Determination of swelling ratios
The completely dried poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM) films were placed in 5-mL vials, and 1 mL of PBS at 37 °C was added. The swollen films were removed after 24 h, and the surface was quickly blotted free of water with filter paper. The films were then weighed and placed in the same bath. The mass measurements were continued until equilibrium was reached. The equilibrium swelling ratio was determined according to the conventional gravimetric method using the following equation: Swelling ratio (%) = [equilibrium swollen weight − initial dried weight) × 100] / [initial dried weight].
Results and discussion
Preparation of poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM)
These findings indicated that HPAN derivatives with controllable compositions of AN-MAA-NIPAM were successfully prepared by radical polymerization. Thus, in this work, we have demonstrated that it is possible to prepare copolymers with distinct compositions, lengths and molecular weights of the hydrophobic PAN segment and the hydrophilic PMAA and/or PNIPAM segments.
Solution properties of poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM)
Surface properties of poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM)
Swelling properties of poly(AN-co-MAA-co-NIPAM), poly(AN-co-MAA) and poly(AN-co-NIPAM)
In this work, we successfully prepared HPAN derivatives with controllable compositions. The properties of the copolymer films depended on the ratio and length of the hydrophobic PAN segment and the hydrophilic PMAA and/or PNIPAM segments. Although future studies will be needed to provide additional biological information associated with cellular studies including cytoxicity, cell growth and proliferation as well as animal experiments, we anticipate that the HPAN derivatives with controllable compositions developed in this study can be potentially used as biomedical hydrogels.
This study was supported by a grant from a Small and Medium Business Administration (S2087373) and Priority Research Centers Program (2010–0028294) through the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP).
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Choi S, Choi W, Kim S, Lee S, Noh I, Kim CW. Purification and biocompatibility of fermented hyaluronic acid for its applications to biomaterials. Biomater Res. 2014;18:6.View ArticleGoogle Scholar
- Kim DY, Kwon DY, Kwon JS, Kim JH, Min BH, Kim MS. Injectable in situ-forming hydrogels for regenerative medicines. Polymer Review. 2015;55:407–52.View ArticleGoogle Scholar
- Kim DY, Kwon DY, Kwon JS, Kim JH, Min BH, Kim MS. Stimuli-responsive injectable in situ–forming hydrogels for regenerative medicines. Polymer Review. 2015;55:407–52.View ArticleGoogle Scholar
- Gupta KC, Haider A, Choi YR, Kang IK. Nanofibrous scaffolds in biomedical applications. Biomater Res. 2014;18:5.View ArticleGoogle Scholar
- Ionov L. 3D microfabrication using stimuli-responsive self-folding polymer films. Polym Rev. 2013;53:92–107.View ArticleGoogle Scholar
- Park JH, Kang HY, Kwon DY, Lee BK, Lee B, Jang JW, et al. Biodegradable poly(lactide-co-glycolide-co-ε-caprolactone) block copolymers – evaluation as drug carriers for a localized and sustained delivery system. J Mater Chem B. 2015;3:8143–53.View ArticleGoogle Scholar
- Wang ZG, Wan LS, Xu ZK. Surface engineerings of polyacrylonitrile-based asymmetric membranes towards biomedical applications: an overview. J Memb Sci. 2007;304:8–23.View ArticleGoogle Scholar
- Seo HW, Kim DY, Kwon DY, Kwon JS, Jin LM, Lee B, et al. Injectable intratumoral hydrogel as 5-fluorouracil drug depot. Biomaterials. 2013;34:2748–57.View ArticleGoogle Scholar
- Wang Z, Zhang Y, Zhang J, Huang L, Liu J, Li YK, et al. Exploring natural silk protein sericin for regenerative medicine: an injectable, photoluminescent, cell-adhesive 3D hydrogel. Scientific Rep. 2014;4:7064.View ArticleGoogle Scholar
- Kwon JS, Kim SW, Kwon DY, Park SH, Son AR, Kim JH, et al. In vivo osteogenic differentiation of human turbinate mesenchymal stem cells in an injectable in situ-forming hydrogel. Biomaterials. 2014;35:5327–46.View ArticleGoogle Scholar
- Son AR, Kim DY, Park SH, Jang JY, Kim KS, Kim BJ, et al. Direct chemotherapeutic dual drug delivery through intra-articular injection for synergistic enhancement of rheumatoid arthritis treatment. Scientific Reports. 2015;5:14713.View ArticleGoogle Scholar
- Oh NW, Jegal J, Lee KH. Preparation and characterization of nanofiltration composite membranes using polyacrylonitrile (PAN). I. Preparation and modification of PAN supports. J Appl Polym Sci. 2001;80:1854–62.View ArticleGoogle Scholar
- Chaudhary BK, Farrell J. Preparation and characterization of homopolymer polyacrylonitrile-based fibrous sorbents for arsenic removal. Environ Eng Sci. 2014;31:593–601.View ArticleGoogle Scholar
- Chen S, Gao H, Chen J, Wu J. Surface modification of polyacrylonitrile fibre by nitrile hydratase from Corynebacterium nitrilophilus. Appl Biochem Biotechnol. 2014;174:2058–66.View ArticleGoogle Scholar
- Chiang YW, Hu CM. Studies of reactions with polymers. VI. The modification of PAN with primary amines. J Polym Sci Part A: Polym Chem. 1990;28:1623–36.View ArticleGoogle Scholar
- Bryjak M, Hodge H, Dach B. Modification of porous polyacrylonitrile membrane. Angew Makromol Chem. 1998;260:25–9.View ArticleGoogle Scholar
- Lohokare HR, Kumbharkar SC, Bhole YS, Kharul UK. Surface modification of polyacrylonitrile based ultrafiltration membrane. J Appl Polym Sci. 2006;101:4378–85.View ArticleGoogle Scholar
- Jindal KK, McDougall J, Woods B, Nowakowski L, Goldstein MB. A study of the basic principles determining the performance of several high-flux dialyzers. Am J Kidney Dis. 1989;14:507–11.View ArticleGoogle Scholar
- Chanard J, Lavaud S, Randoux C, Rieu P. New insights in dialysis membrane biocompatibility: relevance of adsorption properties and heparin binding. Nephrol Dial Transpl. 2003;18:252–7.View ArticleGoogle Scholar
- Czop JK, Austen KF. Properties of glycans that activate the human alternative complement pathway and interact with the human monocyte beta-glucan receptor. J Immunol. 1985;135:3388–93.Google Scholar
- Ramseyer P, Micol LA, Engelhardt EM, Osterheld MC, Hubbel JA, Frey P. In vivo study of an injectabld poly(acrylonitrile)-based hydrogel paste as a bulking agent for the treatment of urinary incontinence. Biomaterials. 2010;31:4613–9.View ArticleGoogle Scholar
- Yeom JS, Hwang B, Yang D, Shin HI, Hahn S. Effect of osteoconductive hyaluronate hydrogels on calvarial bone regeneration. Biomater Res. 2014;18:8.View ArticleGoogle Scholar