Abstract
There is a myriad of ways to crosslink hydrogel wound dressings; however, they require additional steps to remove the residue of the crosslinking agents, or their byproducts in biological environments are toxic. In this study, we studied and characterized the crosslinking of the chitosan hydrogels by various dicarboxylic acids, including oxalic acid, adipic acid, and sebacic acid under vacuum at 90 °C. The concentrations of the crosslinkers in the crosslinked hydrogels are tolerable for the cells, and the membranes can be used after crosslinking without complicated additional steps to remove the unreacted residues. The molar ratio of the crosslinkers was calculated based on the stoichiometry of the chitosan amine groups. Attenuated total reflectance Fourier transform infrared spectroscopy revealed amide linkage formation between amine groups of the chitosan and carboxyl groups of the dicarboxylic acids at 90 °C. The results showed that the chitosan membranes crosslinked with oxalic acid had higher Young's modulus (~ 1042 N/mm2) and ultimate tensile strength (~ 75 N/mm2) in comparison with the other dicarboxylic acids. Moreover, the membranes crosslinked with oxalic acid showed a weight loss of ~ 5.4% after 24 h at double-distilled water, which was drastically lower than that of the others. Thus, oxalic acid was selected as the most effective crosslinker. Cell viability assay, using mouse fibroblast (L929) cells, was conducted on the mechanically optimized membranes. The fibroblast cells successfully attached and spread well on the surface of the membranes. In conclusion, the obtained results suggested oxalic acid as an effective and non-toxic crosslinker for chitosan-based membranes for wound dressing applications.
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Campos MG, Satsangi N, Rawls HR, Mei LH (2009) Chitosan cross‐linked films for drug delivery application. Paper presented at: macromolecular symposia
Zuo P-P, Feng H-F, Xu Z-Z et al (2013) fabrication of biocompatible and mechanically reinforced graphene oxide–chitosan nanocomposite films. Chem Cent J 7(1):39–39
Hsiao Y-C, Chen C-N, Chen Y-T, Yang T-L (2013) Controlling branching structure formation of the salivary gland by the degree of chitosan deacetylation. Acta Biomater 9(9):8214–8223
Chien R-C, Yen M-T, Mau J-L (2016) Antimicrobial and antitumor activities of chitosan from shiitake stipes, compared to commercial chitosan from crab shells. Carbohydr Polym 138:259–264
Tachaboonyakiat W, Sukpaiboon E, Pinyakong O (2014) Development of an antibacterial chitin betainate wound dressing. Polym J 46(8):505–510
Liu Z, Ge X, Lu Y, Dong S, Zhao Y, Zeng M (2012) Effects of chitosan molecular weight and degree of deacetylation on the properties of gelatine-based films. Food Hydrocolloids 26(1):311–317
Hattori H, Ishihara M (2015) Changes in blood aggregation with differences in molecular weight and degree of deacetylation of chitosan. Biomed Mater 10(1):015014
Dashtimoghadam E, Mirzadeh H, Taromi FA, Nyström B (2013) Microfluidic self-assembly of polymeric nanoparticles with tunable compactness for controlled drug delivery. Polymer 54(18):4972–4979
Majedi FS, Hasani-Sadrabadi MM, VanDersarl JJ et al (2014) On-chip fabrication of paclitaxel-loaded chitosan nanoparticles for cancer therapeutics. Adv Funct Mater 24(4):432–441
Meng X, Tian F, Yang J, He C-N, Xing N, Li F (2010) Chitosan and alginate polyelectrolyte complex membranes and their properties for wound dressing application. J Mater Sci Mater Med 21(5):1751–1759
Karbasi S, Khorasani SN, Ebrahimi S, Khalili S, Fekrat F, Sadeghi D (2016) Preparation and characterization of poly(hydroxy butyrate)/chitosan blend scaffolds for tissue engineering applications. Adv Biomed Res 5:177
Kojima K, Okamoto Y, Miyatake K, Kitamura Y, Minami S (1998) Collagen typing of granulation tissue induced by chitin and chitosan. Carbohydr Polym 37(2):109–113
Ueno H, Mori T, Fujinaga T (2001) Topical formulations and wound healing applications of chitosan. Adv Drug Deliv Rev 52(2):105–115
Benhabiles M, Salah R, Lounici H, Drouiche N, Goosen M, Mameri N (2012) Antibacterial activity of chitin, chitosan and its oligomers prepared from shrimp shell waste. Food Hydrocolloids 29(1):48–56
Dragostin OM, Samal SK, Dash M et al (2016) New antimicrobial chitosan derivatives for wound dressing applications. Carbohydr Polym 141:28–40
Moghadas B, Dashtimoghadam E, Mirzadeh H, Seidi F, Hasani-Sadrabadi MM (2016) Novel chitosan-based nanobiohybrid membranes for wound dressing applications. RSC Adv 6(10):7701–7711
Je J-Y, Kim S-K (2006) Chitosan derivatives killed bacteria by disrupting the outer and inner membrane. J Agric Food Chem 54(18):6629–6633
Helander IM, Nurmiaho-Lassila EL, Ahvenainen R, Rhoades J, Roller S (2001) Chitosan disrupts the barrier properties of the outer membrane of Gram-negative bacteria. Int J Food Microbiol 71(2):235–244
Kim S-K (2010) Chitin, chitosan, oligosaccharides and their derivatives: biological activities and applications. CRC Press, Boca Raton
López-Mata MA, Ruiz-Cruz S, Silva-Beltrán NP, Ornelas-Paz JJ, Zamudio-Flores PB, Burruel-Ibarra SE (2013) Physicochemical, antimicrobial and antioxidant properties of chitosan films incorporated with carvacrol. Molecules 18(11):13735–13753
Fernandez-Saiz P, Lagaron J, Ocio M (2009) Optimization of the film-forming and storage conditions of chitosan as an antimicrobial agent. J Agric Food Chem 57(8):3298–3307
Li Q, Dunn E, Grandmaison E, Goosen M (1992) Applications and properties of chitosan. J Bioact Compat Polym 7(4):370–397
Kamoun EA, Chen X, Eldin MSM, Kenawy E-RS (2015) Crosslinked poly(vinyl alcohol) hydrogels for wound dressing applications: a review of remarkably blended polymers. Arab J Chem 8(1):1–14
Elsner JJ, Shefy-Peleg A, Zilberman M (2010) Novel biodegradable composite wound dressings with controlled release of antibiotics: microstructure, mechanical and physical properties. J Biomed Mater Res B Appl Biomater 93(2):425–435
Cai M, Gong J, Cao J, Chen Y, Luo X (2013) In situ chemically crosslinked chitosan membrane by adipic acid. J Appl Polym Sci 128(5):3308–3314
Muzzarelli RA (2009) Genipin-crosslinked chitosan hydrogels as biomedical and pharmaceutical aids. Carbohydr Polym 77(1):1–9
Chen P-H, Kuo T-Y, Liu F-H et al (2008) Use of dicarboxylic acids to improve and diversify the material properties of porous chitosan membranes. J Agric Food Chem 56(19):9015–9021
ASTM D882-18 (2018) Standard test method for tensile properties of thin plastic sheeting. ASTM International, West Conshohocken, PA. https://doi.org/10.1520/D0882-18, www.astm.org.
Jamalpoor Z, Mirzadeh H, Joghataei MT, Zeini D, Bagheri-Khoulenjani S, Nourani MR (2015) Fabrication of cancellous biomimetic chitosan-based nanocomposite scaffolds applying a combinational method for bone tissue engineering. J Biomed Mater Res Part A 103(5):1882–1892
Bonakdar S, Emami SH, Shokrgozar MA, Farhadi A, Ahmadi SAH, Amanzadeh A (2010) Preparation and characterization of polyvinyl alcohol hydrogels crosslinked by biodegradable polyurethane for tissue engineering of cartilage. Mater Sci Eng C 30(4):636–643
ISO B. 10993-5 (1999) Biological evaluation of medical devices. Tests for in vitro cytotoxicity
Sadeghi D, Karbasi S, Razavi S, Mohammadi S, Shokrgozar MA, Bonakdar S (2016) Electrospun poly(hydroxybutyrate)/chitosan blend fibrous scaffolds for cartilage tissue engineering. J Appl Polym Sci. https://doi.org/10.1002/app.44171
Mansouri M, Nazarpak MH, Solouk A, Akbari S, Hasani-Sadrabadi MM (2017) Magnetic responsive of paclitaxel delivery system based on SPION and palmitoyl chitosan. J Magn Magn Mater 421:316–325
Yalçınkaya S, Demetgül C, Timur M, Çolak N (2010) Electrochemical synthesis and characterization of polypyrrole/chitosan composite on platinum electrode: its electrochemical and thermal behaviors. Carbohydr Polym 79(4):908–913
Ritthidej GC, Phaechamud T, Koizumi T (2002) Moist heat treatment on physicochemical change of chitosan salt films. Int J Pharm 232(1):11–22
Ghosh A, Ali MA (2012) Studies on physicochemical characteristics of chitosan derivatives with dicarboxylic acids. J Mater Sci 47(3):1196–1204
Tsao CT, Chang CH, Li YD et al (2011) Development of chitosan/dicarboxylic acid hydrogels as wound dressing materials. J Bioact Compat Polym 26(5):519–536
Szymańska E, Winnicka K (2015) Stability of chitosan—a challenge for pharmaceutical and biomedical applications. Mar Drugs 13(4):1819–1846
Güneş S, Tıhmınlıoğlu F (2017) Hypericum perforatum incorporated chitosan films as potential bioactive wound dressing material. Int J Biol Macromol 102:933–943
Tığlı RS, Karakeçili A, Gümüşderelioğlu M (2007) In vitro characterization of chitosan scaffolds: influence of composition and deacetylation degree. J Mater Sci Mater Med 18(9):1665–1674
Ma J, Wang H, He B, Chen J (2001) A preliminary in vitro study on the fabrication and tissue engineering applications of a novel chitosan bilayer material as a scaffold of human neofetal dermal fibroblasts. Biomaterials 22(4):331–336
Tyliszczak B, Drabczyk A, Kudłacik-Kramarczyk S, Bialik-Wąs K, Sobczak-Kupiec A (2017) In vitro cytotoxicity of hydrogels based on chitosan and modified with gold nanoparticles. J Polym Res 24(10):153
Tyliszczak B, Drabczyk A, Kudłacik-Kramarczyk S, Bialik-Wąs K, Kijkowska R, Sobczak-Kupiec A (2017) Preparation and cytotoxicity of chitosan-based hydrogels modified with silver nanoparticles. Colloids Surf B 160:325–330
Acknowledgements
The authors would like to express their sincere gratitude to Iran National Science Foundation (INSF) for supporting this research and Ms. Sama Ghalei for her openhanded support and assistance.
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Moghadas, B., Solouk, A. & Sadeghi, D. Development of chitosan membrane using non-toxic crosslinkers for potential wound dressing applications. Polym. Bull. 78, 4919–4929 (2021). https://doi.org/10.1007/s00289-020-03352-8
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DOI: https://doi.org/10.1007/s00289-020-03352-8