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Development of Absorbents Based on Polymeric Nanocomposites for Uraemic Toxin Sorption

Xiong, Siyu; (2022) Development of Absorbents Based on Polymeric Nanocomposites for Uraemic Toxin Sorption. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

More than 3 million patients are treated for kidney failure worldwide. Azotaemic uraemic toxins, such as 3-indoxyl sulfate (IS), accumulate in patients with chronic kidney disease (CKD). The IS has been reported to accelerate CKD progression and increase the risk of cardiovascular disease by increasing oxidative stress. Haemodialysis, the most commonly used treatment, has a 90% lower clearance of the indoxyl sulfate from blood compared to urea, resulting in prolonged dialysis session time, which promotes the need and development of wearable artificial kidney (WAK) devices with better portability and more comfortable filtration intensity to increase the quality of life. Moreover, conventional haemodialysis requires large amounts of water and generates mountains of non-recyclable plastic waste. To improve the environmental footprint, dialysis treatments need to develop absorbents to regenerate the waste dialysate or use absorbents to directly absorb uraemic toxins from the blood to avoid dialysate usage. Whereas conventional dialysis clears water-soluble toxins, it is ineffective in clearing protein-bound uraemic toxins (PBUTs), such as indoxyl sulfate (IS). Thus, developing absorption devices to remove both water-soluble and PBUTs would be advantageous. Recent research has developed and studied highly porous materials such as zeolite, porous carbon, and metal-organic frameworks for uraemic toxin absorption. Most of these porous materials absorb uraemic toxins based on their molecular sizes instead of their chemical structures. Alternative chitosan-based absorbents and related improvements are proposed in this thesis as a proof of concept for renal filtration applications, including uraemic toxin removal and dialysate regeneration for wearable dialysis devices. In this thesis, a conventional electrospinning setup was adapted onto a commercial 3D printing system to fabricate the polycaprolactone-based composite fibrous membrane in a programmable pattern for indoxyl sulfate absorption studies. A single unit (Φ 2.0mm × L 20mm) of polycaprolactone/chitosan (PCL/CS) composite fibrous absorbent material has achieved 28% clearance of free-form indoxyl sulfate molecules at both 40 mg/L and 5 mg/L initial IS concentration in a single pass within 1 hour. However, the albumin-bound IS absorption of the PCL/CS fibrous absorbent was limited. Porous surface was then introduced onto the PCL/CS electrospun nanofibers to enhance the albumin-bound IS absorption performance of the electrospun PCL/CS mesh by applying phase separation and sacrificed material approaches. The albumin-bound IS absorption performance of the porous PCL/CS fibres was tested. Although the albumin-bound IS absorption performance of these PCL/CS porous fibres were limited, the investigations on these porous PCL/CS electrospun fibres have provided experiences and understanding on the interactions between the chitosan composite fibres and indoxyl sulfate, and also allowed re-thinking on limitations of electrospun absorbents, which are helpful for the absorbent design in wearable dialysis applications in the future. Finally, vapour induced phase separation (VIPS) was used in the absorbent design to produce polycaprolactone/chitosan (PCL/CS) composite symmetric porous monoliths with extra porous carbon additives to increase albumin-bound IS absorption and allow additional creatinine absorption. Moreover, these easy-to-fabricated porous monoliths can be formed into required geometry. The PCL/CS porous monoliths absorbed 436 μg/g of albumin-bound IS and 2865 μg/g of creatinine in a single-pass perfusion model within 1 hour. This porous PCL/CS monolith could potentially be used to absorb uraemic toxins, including PBUTs, thus allowing the regeneration of waste dialysate and developing a new generation of environmentally sustainable dialysis treatments, including wearable devices

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Development of Absorbents Based on Polymeric Nanocomposites for Uraemic Toxin Sorption
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10142964
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