Biofriendly chitosan-based high-efficiency dialysis membrane
Introduction
Chronic/acute kidney disease is among the top ten most fatal diseases in the world. An aging population continuously contributes to the increase in the number of patients and mortality rate. Currently, kidney disease affects approximately 600 million people worldwide, and the number of patients continues to increase at an annual rate of 6–7 % [1]. Kidney failure causes increased generation and accumulation of urea and other metabolic waste products, which are difficult to metabolize or excrete. Consequently, when urea concentration in the body reaches >300 ppm, uremia occurs. The most commonly adopted treatment method for kidney disease is hemodialysis, during which blood is pumped out of the body by a machine and filtered for the removal of waste products and excess water before its return to the body. Although hemodialysis is highly effective, it requires surgical intervention by professional nurses on a regular basis. Therefore, patients have to make frequent trips to the hospital and accommodate the availability of hospital resources to undergo hemodialysis for long durations. This may predispose patients to hypotension, muscle spasms, and dialysis disequilibrium syndrome, which cause symptoms such as nausea and vomiting. Therefore, home dialysis has become a convenient alternative for acute and chronic kidney disease patients of various age groups. However, it requires long durations of caregiver support and increasingly complex dialysis techniques as the disease aggravates over time [2]. Therefore, there is an urgent need for methods that can achieve high adsorption rates within a short period of time. In particular, improving the adsorption time and efficiency of dialysis membranes is a significant challenge in the field of biomedical engineering.
Presently, adsorbents are highly effective in urea adsorption, with activated carbon being the most widely used in clinical applications. In a proposed cold dialysate regeneration system using cold dialysate and two activated carbon columns switched alternatively between adsorption and desorption, a urea reduction ratio (URR) of 60.9 % was achieved within 4 h [3]. When urea was adsorbed using spherical activated carbon, adsorption equilibrium was achieved within 50 min; however, the adsorption capacity was limited to 2 mg/g [4]. In a urea adsorption experiment performed with chitosan-modified montmorillonite clay, the URR remained below 80 % despite an experimental duration of 5 h [5]. Alternatively, adsorption equilibrium was achieved within 4 h when urea was adsorbed using oxidized starch nanoparticles; however, the adsorption capacity was merely 60 mg/g at a urea concentration of 500 ppm [6].
Chitosan is a natural, multifunctional, and environmentally friendly material. It possesses good biocompatibility, is almost non-toxic, and rarely triggers allergic reactions [7], [8]. These excellent properties have led to its widespread use in biological applications. For instance, chitosan-based polymers synthesized by electrospinning significantly improve biocompatibility and biodegradability of hemostatic agents in vivo, which may enhance their effects during surgery [9]. Chitosan nanoparticles that were produced using different crosslinkers were evaluated in vitro to determine the effects of different crosslinking parameters on its hemocompatibility, biodegradability, serum stability, cytotoxicity, and cell viability. The results indicated that the nanoparticles were non-toxic with a good degree of biodegradability and hemocompatibility [10]. In another study, chitosan nanofibrous membranes were prepared by electrospinning using phosphate ions as crosslinkers, and their potential application in wound healing patches was explored. Results of a cell adhesion experiment demonstrated that the use of phosphate ions for crosslinking significantly enhanced the biocompatibility of the patches, leading to the promotion of cell viability [11]. The most prominent feature of chitosan is its abundance of carboxyl and amine groups, and the source of its high absorbability, which enables its utilization in Biomedical research, wastewater treatment, food technology. For instance, novel aerogel graphene oxide composite globules prepared using chitosan as a crosslinking agent achieved a maximum adsorption capacity of 3190 mg/g toward methylene blue; to the best of our knowledge, this is the highest adsorption capacity reported in literature [12]. Chitosan foam prepared by lyophilization served as a novel amphoteric adsorbent with high adsorption capacities for both cationic and anionic dyes [13]. Hydrogels formed from the grafting of chitosan with cellulose exhibited good elasticity, excellent resilience, and high capacity for dye adsorption. The gels could also be easily collected after adsorption owing to their biodegradable nature [14]. By inducing changes in the chitosan backbone through crosslinking and introducing new functional groups for adsorption through grafting, the adsorption site density can be increased. In addition, the adsorption sites and/or adsorption mechanisms can be modified to provide active functional groups [15], [16], [17], [18]. Furthermore, crosslinking reactions using crosslinkers, such as glutaraldehyde [19], [20], ethylenediaminetetraacetic acid (EDTA) [21], [22], and glycine [23], [24], can effectively increase the adsorption ability of chitosan.
According to the advantages of easy modification of the hydroxyl and amino groups in the chitosan molecule, functional groups are introduced to improve its functionality and expand its application range [25], [26]. The modification can be divided into two parts: physical modification and chemical modification. In the part of physical modification, this study cited the use of sodium tripolyphosphate (STPP) as a cross-linking agent, which is a hydrophilic non-toxic reagent compared to the toxic reagents used in the past (glutaraldehyde [27], [28], epichlorohydrin [29], sodium citrate [30], etc.), And connect the molecular chains in high molecular polymers. When not cross-linked, the molecular chain can be loosened at will; after cross-linking, the molecular chain is stronger. In the chemical modification part, the main purpose is to enhance the adsorption capacity and chemical resistance and will not change the basic skeleton of chitosan, but will maintain the original physical and chemical properties. Such as oligomerization, alkylation, quternization [31], hydroxyalkylation [32], carboxyalkylation [33], thiolation [34]… and many various modifications have been studied [35].
The acceptable URR of dialysis membranes is 60 %–65 %, and the duration of a dialysis session is usually 4–5 h. Long-duration dialysis reduces the physical strength of patients [36] and may lead to increased urea replenishment under conditions of inadequate adsorption efficiency even when the dialysis time is prolonged. In the present study, we aimed to enhance the adsorption efficiency of chitosan through physical and chemical modifications to achieve a target URR of >80 % within 2 h for a urea concentration of 500 ppm.
Section snippets
Chemical and physical modification
Chitosan modification was performed using chemical and physical methods. Chemical modifications included carboxylation and amination, which are described as follows: (1) carboxylation: Chitosan (2 g) (degree of deacetylation: 90 %, average molecular weight: 100–130 kDa; Charming and Beauty Co., Ltd., Taiwan) was placed in chloroacetic acid. Aqueous sodium hydroxide (0.1 N) was used to maintain a pH of 8, and distilled water was subsequently used for washing to neutral pH to obtain carboxylated
Parameter optimization of chitosan-based dialysis membranes
Water permeability is a key parameter for evaluating the applicability of the prepared chitosan-coated filter papers as alternatives to current dialysis membranes [49]. Under the condition that a minimum flow rate of 5 cm3/s for dialysis membranes was achieved, we attempted to optimize the chitosan concentration and number of coatings of the chitosan-coated filter papers. An increase in chitosan concentration caused an increase in the coat weight and the adsorbed adsorbate amount; however, the
Conclusion
Our research objective is to increase the urea removal rate to over 80 % within 2 h. The results indicates that the number of adsorption sites in chitosan could be increased by modification. With chemical modification, the URR of the membrane-coated filter increased by nearly 50 % after 2 h of adsorption. However, the number of adsorption sites did not significantly increase. Physical modification was carried out using crosslinking agents, which increased the bonding between the molecular
CRediT authorship contribution statement
Shih-Chen Shi: Conceptualization, Methodology, Resources, Writing- Reviewing and Editing, Supervision, Project administration, Funding acquisition.
Yu-Wen Chang: Validation, Formal analysis, Investigation, Data Curation, Writing- Original draft.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
This work was supported by the Ministry of Science and Technology, Taiwan (grant number MOST 110-2221-E-006-150). The authors gratefully acknowledge the use of EM000600 of MOST 110-2731-M-006-001.
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