Preparation, Characterization, and In Vitro Hemocompatibility of Glutaraldehyde-Crosslinked Chitosan/Carboxymethylcellulose as Hemodialysis Membrane

Khabibi Khabibi(1), Dwi Siswanta(2), Mudasir Mudasir(3*)

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia; Department of Chemistry, Faculty of Sciences and Mathematics, Diponegoro University, Jl. Prof. H. Soedarto, S.H., Tembalang, Semarang 50275, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia
(*) Corresponding Author


This study aims to examine the manufacture, characterization, and in vitro hemocompatibility of glutaraldehyde-crosslinked chitosan/carboxymethyl cellulose (CS/CMC-GA) as a hemodialysis membrane. The CS/CMC-GA membrane was prepared using the phase inversion method with 1.5% CS and 0.1% CMC. The chitosan was crosslinked with glutaraldehyde in various monomers ratios, and the membranes formed were characterized by FTIR, SEM, and TGA. Furthermore, the hydrophilicity, swelling, porosity, mechanical strength, and dialysis performance of the membranes against urea and creatinine were systematically examined, and their in-vitro hemocompatibility tests were also conducted. The results showed that the CS/CMC-GA membranes have higher hydrophilicity, swelling, porosity, mechanical strength, and better dialysis performance against urea and creatinine than chitosan without modification. In addition, the hemocompatibility test indicated that the CS/CMC-GA membranes have lower values of protein adsorption, thrombocyte attachment, hemolysis ratio, and partial thromboplastin time (PTT) than that of pristine chitosan. Based on these results, the CC/CMC-GA membranes have better hemocompatibility and the potential to be used as hemodialysis membranes.


chitosan; CMC; membrane; hemodialysis

Full Text:

Full Text PDF


[1] Kaleekkal, N.J., Thanigaivelan, A., Tarun, M., and Mohan, D., 2015, A functional PES membrane for hemodialysis–Preparation, characterization and biocompatibility, Chin. J. Chem. Eng., 23 (7), 1236–1244.

[2] Tu, M.M., Xu, J.J., and Qiu, Y.R., 2019, Surface hemocompatible modification of polysulfone membrane via covalently grafting acrylic acid and sulfonated hydroxypropyl chitosan, RSC Adv., 9 (11), 6254–6266.

[3] Irfan, M., Irfan, M., Shah, S.M., Baig, N., Saleh, T.A., Ahmed, M., Naz, G., Akhtar, N., Muhammad, N., and Idris, A., 2019, Hemodialysis performance and anticoagulant activities of PVP-k25 and carboxylic-multiwall nanotube composite blended polyethersulfone membrane, Mater. Sci. Eng., C, 103, 109769.

[4] Song, H., Ran, F., Fan, H., Niu, X., Kang, L., and Zhao, C., 2014, Hemocompatibility and ultrafiltration performance of surface-functionalized polyethersulfone membrane by blending comb-like amphiphilic block copolymer, J. Membr. Sci., 471, 319–327.

[5] Yu, X., Shen, L., Zhu, Y., Li, X., Yang, Y., Wang, X., Zhu, M., and Hsiao, B.S., 2017, High performance thin-film nanofibrous composite hemodialysis membranes with efficient middle-molecule uremic toxin removal, J. Membr. Sci., 523, 173–184.

[6] Lusiana, R.A., Sangkota, V.D.A., Sasongko, N.A., Gunawan, G., Wijaya, AR, Santosa, S.J., Siswanta, D., Mudasir, M., Abidin, M.N.Z., Mansur, S., and Othman, M.H.D., 2020, Permeability improvement of polyethersulfone-polyethylene glycol (PEG-PES) flat sheet type membranes by tripolyphosphate-crosslinked chitosan (TPP-CS) coating, Int. J. Biol. Macromol., 152, 633–644.

[7] Campelo, C.S., Lima, L.D., Rebêlo, L.M., Mantovani, D., Beppu, M.M., and Vieira, R.S., 2016, In vitro evaluation of anti-calcification and anti-coagulation on sulfonated chitosan and carrageenan surfaces, Mater. Sci. Eng., C, 59, 241–248.

[8] Amiji, M.M., 1998, Platelet adhesion and activation on an amphoteric chitosan derivative bearing sulfonate groups, Colloids Surf., B, 10 (5), 263–271.

[9] Rafique, A., Mahmood Zia, K., Zuber, M., Tabasum, S., and Rehman, S., 2016, Chitosan functionalized poly(vinyl alcohol) for prospects biomedical and industrial applications, Int. J. Biol. Macromol., 87, 141–154.

[10] Teotia, R.S., Kalita, D., Singh, A.K., Verma, S.K., Kadam, S.S., and Bellare, J.R., 2015, Bifunctional polysulfone-chitosan composite hollow fiber membrane for bioartificial liver, ACS Biomater. Sci. Eng., 1 (6), 372–381.

[11] Hoenich, N.A., 2004, Update on the biocompatibility of hemodialysis membranes, Hong Kong J. Nephrol., 6 (2), 74–78.

[12] Balan, V., and Verestiuc, L., 2014, Strategies to improve chitosan hemocompatibility: A review, Eur. Polym. J., 53, 171–188.

[13] Amiji, M.M., 1996, Surface modification of chitosan membranes by complexation-interpenetration of anionic polysaccharides for improved blood compatibility in hemodialysis, J. Biomater. Sci., Polym. Ed., 8 (4), 281–298.

[14] Lusiana, R.A., Protoningtyas, W.P., Wijaya, A.R., Siswanta, D., Mudasir, and Santosa, S.J., 2017, Chitosan-tripolyphosphate (CS-TPP) synthesis through crosslinking process: The effect of concentration towards membrane mechanical characteristic and urea permeation, Orient. J. Chem., 33 (6), 2913–2919.

[15] Cahyaningrum, S.E., Herdyastuti, N., Firdausa, A., and Yanrita, D., 2017, Synthesis and characterization chitosan-glutaraldehyde alginate blends for candidate hemodialysis membrane, Rasayan J. Chem., 10 (3), 959–966.

[16] Lusiana, R.A., Pambudi, G.A., Sari, F.N., Widodo, D.S., and Khabibi, K., 2019, Grafting of heparin on blend membrane of citric acid crosslinked chitosan/polyethylene glycol-poly vinyl alcohol (PVA-PEG), Indones. J. Chem., 19 (1), 151–159.

[17] Zhu, L., Song, H., Wang, J., and Xue, L., 2017, Polysulfone hemodiafiltration membranes with enhanced anti-fouling and hemocompatibility modified by poly(vinyl pyrrolidone) via in situ crosslinked polymerization, Mater. Sci. Eng., C, 74, 159–166.

[18] Siahaan, P., Sasongko, N.A., Lusiana, R.A., Prasasty, V.D., and Martoprawiro, M.A., 2021, The validation of molecular interaction among dimer chitosan with urea and creatinine using density functional theory: In application for hemodialysis membrane, Int. J. Biol. Macromol., 168, 339–349.

[19] Tongdeesoontorn, W., Mauer, L.J., Wongruong, S., Sriburi, P., and Rachtanapun, P., 2011, Effect of carboxymethyl cellulose concentration on physical properties of biodegradable cassava starch-based films, Chem. Cent. J., 5, 1–8.

[20] Xiang, T., Xie, Y., Wang, R., Wu, M.B., Sun, S.D., and Zhao, C.S., 2014, Facile chemical modification of polysulfone membrane with improved hydrophilicity and blood compatibility, Mater. Lett., 137, 192–195.

[21] Wang, F.J., Lu, F.S., Cui, M., and Shao, Z.Q., 2015, Biocompatible microcapsule of carboxymethyl cellulose/chitosan as drug carrier, Adv. Mater. Res., 1118, 227–236.

[22] Fajarwati, F.I., Sugiharto, E., and Siswanta, D., 2011, Film of chitosan-carboxymethyl cellulose polyelectrolyte complex as methylene blue adsorbent, Eksakta Jurnal Ilmu-Ilmu MIPA, 16 (1), 36–45.

[23] Poon, L., Wilson, L.D., and Headley, J.V., 2014, Chitosan-glutaraldehyde copolymers and their sorption properties, Carbohydr. Polym., 109, 92–101.

[24] Abidin, M.N.Z., Goh, P.S., Ismail, A.F., Othman, M.H.D., Hasbullah, H., Said, N., Kadir, S.H.S.A., Kamal, F., Abdullah, M.S., and Ng, B.C., 2016, Antifouling polyethersulfone hemodialysis membranes incorporated with poly (citric acid) polymerized multi-walled carbon nanotubes, Mater. Sci. Eng., C, 68, 540–550.

[25] Gao, A., Liu, F., and Xue, L., 2014, Preparation and evaluation of heparin-immobilized poly (lactic acid) (PLA) membrane for hemodialysis, J. Membr. Sci., 452, 390–399.

[26] Monteiro Jr., O.A.C., and Oyrton, A.C., 1999, Some studies of crosslinking chitosan–glutaraldehyde interaction in a homogeneous system, Int. J. Biol. Macromol., 26 (2-3), 119–128.

[27] Beppu, M.M., Vieira, R.S., Aimoli, C.G., and Santana, C.C., 2007, Crosslinking of chitosan membranes using glutaraldehyde: Effect on ion permeability and water absorption, J. Membr. Sci., 301 (1-2), 126–130.

[28] Sasongko, N.A., Siahaan, P., Lusiana, R.A., and Prasasty, V., 2020, Understanding the interaction of polysulfone with urea and creatinine at the molecular level and its application for hemodialysis membrane, J. Phys. Conf. Ser., 1524, 012084.

[29] Amri, C., Mudasir, M., Siswanta, D., and Roto, R., 2016, In vitro hemocompatibility of PVA-alginate ester as a candidate for hemodialysis membrane, Int. J. Biol. Macromol., 82, 48–53.

[30] Chan, K.H., Wong, E.T., Khan, M.I., Idris, A., and Yusof, N.M., 2014, Fabrication of polyvinylidene difluoride nano-hybrid dialysis membranes using functionalized multiwall carbon nanotube for polyethylene glycol (hydrophilic additive) retention, J. Ind. Eng. Chem., 20, 3744–3753.

[31] Irfan, M., Idris, A., Yusof, N.M., Khairuddin, N.F.M., and Akhmal, H., 2014, Surface modification and performance enhancement of nano-hybrid f-MWCNT/PVP90/PES hemodialysis membranes, J. Membr. Sci., 467, 73–84.

[32] Ren, Z., Chen, G., Wei, Z., Sang, L., and Qi, M., 2013, Hemocompatibility evaluation of polyurethane film with surface-grafted poly(ethylene glycol) and carboxymethyl-chitosan, J. Appl. Polym. Sci., 127 (1), 308–315.

[33] Tang, M., Xue, J., Yan, K., Xiang, T., Sun, S., and Zhao, C., 2012, Heparin-like surface modification of polyethersulfone membrane and its biocompatibility, J. Colloid Interface Sci., 386 (1), 428–440.

[34] Li, L., Cheng, C., Xiang, T., Tang, M., Zhao, W., Sun, S., and Zhao, C., 2012, Modification of polyethersulfone hemodialysis membrane by blending citric acid grafted polyurethane and its anticoagulant activity, J. Membr. Sci., 405-406, 261–274.


Article Metrics

Abstract views : 1901 | views : 1908

Copyright (c) 2021 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.


Indonesian Journal of Chemistry (ISSN 1411-9420 / 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Analytics View The Statistics of Indones. J. Chem.