Regenerative Biomaterials
·
2025
·
IF 8.1
Wang Shujing,Liang Jiahao,Chen Yu,Liu Xianda,Tong Dongmei,Li Yupei,Zhao Weifeng,Su Baihai,Zhao Changsheng
Conventional hemodialysis and hemodiafiltration prove less effective at removing protein-bound uremic toxins (PBUTs) from the bloodstream of end-stage renal disease patients, primarily because PBUTs cannot pass through the small pores in the polymeric membranes. Hemoperfusion is an extracorporeal blood purification technique that employs an adsorption mechanism to remove multiple uremic toxins from such patients. Yet, the efficacy of hemoperfusion is constrained by some limitations of contemporary adsorbents, such as suboptimal capacity to adsorb PBUTs and poor hemocompatibility, presenting significant barriers for their clinical application. To address these challenges, we engineered a tailored hemoperfusion adsorbent by compounding sulfonated polysulfone (SPSf) and polyethyleneimine (PEI) into polyethersulfone (PES) microspheres to effectively capture and remove PBUTs through electrostatic interactions. Specially, we introduced sulfuric acid into the coagulation bath to increase the adsorption amount of the developed adsorbent (H-PES/SPSf@PEI microspheres), to neutralize strong positive charge of PEI, and to improve hemocompatibility. The tailored H-PES/SPSf@PEI microspheres neither damage blood cells nor activate the complement pathway when they contact with human blood. Moreover, H-PES/SPSf@PEI microspheres have a high adsorption amount towards major PBUTs, including hippuric acid (HA, 34.24 mg/g), 3-indoleacetic acid (IAA, 49.19 mg/g), p-cresol sulfate (PCS, 40.31 mg/g) and indoxyl sulfate (IS, 128.67 mg/g) by fitting adsorption isotherms. In a simulated hemoperfusion setting, the removal ratio of IS, IAA, PCS and HA by H-PES/SPSf@PEI microspheres reach nearly 75.33%, 41.73%, 44.36%, and 21.11%, respectively, with 47.89% of IS, 40.64% of IAA, 44.42% of PCS and 37.35% of HA being removed from BSA solution. In conclusion, H-PES/SPSf@PEI microspheres hold a potential to eliminate PBUTs from patients with end-stage renal disease.
研究领域:
生物医学工程
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肾脏病学
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材料科学
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生物工程
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血液透析
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DOI
PubMed
高影响因子
Aggregate
·
2024
·Vol. 5
·期 4
·e542
·
IF 13.9
Xiaomin Ye,Chaoyu Yang,Li Wang,Qihui Fan,Luoran Shang,Fangfu Ye
Adsorbents with high adsorption efficiency and excellent biosafety for biomedical applications are highly required. MXene is a promising candidate owning these advantages, yet pristine MXene faces dilemmas including insufficient utility of surface site as well as limited processibility. Here, we develop MXene-encapsulated porous microcapsules via microfluidics. The microcapsules have a biomass hydrogel shell that provides robust support for MXene in the core, by which the microcapsules are endowed with high MXene dosage and remarkable biosafety. Additionally, the MXene nanoflakes assemble into a three-dimensional network via metal ion-induced gelation, thereby avoiding restacking and significantly improving surface utilization. Moreover, a freeze-pretreatment of the microcapsules during preparation results in the formation of a macroporous structure in the shell, which can facilitate the diffusion of the target molecules. These features, combined with additional magneto-responsiveness rendered by the incorporation of magnetic nanoparticles, contribute to prominent performances of the microcapsules in cleaning uremia toxins including creatinine, urea, and uric acid. Thus, it is anticipated that the MXene-encapsulated microcapsules will be promising adsorbents in dialysis-related applications, and the combination of microfluidic encapsulation with metal ion gelation will provide a novel approach for construction of hybrid MXene materials with desired functions.
研究领域:
生物医学工程
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材料科学
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肾脏病学
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DOI
高影响因子
Biomass Conversion and Biorefinery
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2021
·Vol. 13
·期 13
·11499-11511
·
IF 4.987
Wang Wei,Wang Zhijuan,Li Kai,Liu Yuxin,Xie Delong,Shan Shaoyun,He Liang,Mei Yi
Numerous studies have shown that patients with COVID-19 have a high incidence of renal dysfunction. However, the dialysis supplies, including dialysates, are also severely inadequate in hospitals at the pandemic centers. Therefore, there is an urgent need to develop materials that can efficiently and rapidly remove toxins and thus regenerate dialysate to make this vital resource remains readily available. In this work, by simple carbonization and activation treatment, the porous activated carbon from waste rubber seed shell (RAC) was prepared. The adsorption results showed that the maximum adsorption capacities of the obtained RAC for creatinine and uric acid were 430 mg/g and 504 mg/g, respectively. Significantly, the adsorption process can be close to the equilibrium state within 0.5 h, which proved the ultra-fast adsorption response capacity of RAC. Further, the thermodynamics analysis results showed that both the creatinine and uric acid adsorption processes were monolayer, exothermic, and spontaneous. The adsorption kinetics results indicated that the adsorption process of the two uremic toxins followed the pseudo-second-order rate model and was dominated by chemisorption. The instrument analysis results reflected the efficient adsorption of the RAC for the above uremic toxins which might be due to the dipole–dipole interaction between the dipolar oxygen-containing groups of the surface of RAC and the dipoles of the toxins. Moreover, the formed hydrogen bonds between the oxygen groups and the toxins also played an important role. In all, the as-prepared RAC has the potential to efficiently remove major toxins from the dialysate and can be used in in vitro dialysis of numerous patients during the current COVID-19 pandemic.
研究领域:
医学
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材料科学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Baizhao Peng,Jiaojiao Dai,Shuai Ji,Ying Yang,Anna Zuo,Shanhua Xu,Wen Fang,Dexian Li,Yanting You,Zihao Jiang,Chuanghai Wu,Hiu Yee Kwan,Xiaoshan Zhao,Yanyan Liu
Background Hyperuricemia (HUA) is closely associated with gut dysbiosis, yet the role of microbial metabolism in hyperuricemic nephropathy (HN) remains poorly understood. Quercetin has shown urate-lowering and nephroprotective effects, but its therapeutic mechanisms, particularly in modulating the gut microbiome and microbial metabolism, remain elusive. Purpose This study investigates the therapeutic effects of quercetin on HN and explores its role in regulating host-microbial co-metabolism. Methods A spontaneous HUA rat model (Uox-/- rats) was used to evaluate the therapeutic effect of quercetin. Multi-omics analyses, including gut microbiome profiling, peripheral untargeted metabolome, and targeted quantification of gut bacteria-derived uremic toxins, were performed. An integrated network analysis was conducted to uncover potential host-microbe metabolic interactions. Results Quercetin treatment significantly reduced serum uric acid, creatinine, and blood urea nitrogen, ameliorated renal inflammation, fibrosis and oxidative stress, and improved gut dysbiosis and intestinal barrier dysfunction. Notably, high-dose quercetin downregulated Blautia, a key gut bacterium associated with uremic toxin production, and suppressed microbial phenylalanine metabolism, leading to decreased levels of gut bacteria-derived nephrotoxic metabolites (e.g., 3-phenyllactic acid, hippuric acid, and N-acetyl-L-phenylalanine). These uremic toxins were positively correlated with markers of kidney injury and proinflammatory cytokines. Mechanistically, quercetin modulated microbial enzymatic pathways involved in phenylalanine metabolism, thereby disrupting the formation of nephrotoxic metabolites and alleviating renal damage. Conclusions This study provides multi-omics evidence that quercetin ameliorates HN by regulating gut dysfunctions and decreasing gut bacteria-derived uremic toxins through host-microbial co-metabolism. These findings highlight the therapeutic potential of microbiota-targeted interventions in HUA-associated kidney diseases.
研究领域:
医学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2021
·Vol. 110
·期 4
·976-983
·
IF 4.396
Yuqi Shen,Yue Shen,Jiaolun Li,Feng Ding,Yifeng Wang
Protein-bound uremic toxins (PBUTs) are significant toxins that are closely related to the prognosis of chronic kidney disease. They cannot be effectively removed by conventional dialysis therapies due to their high albumin binding affinity. Our previous research revealed that cationic liposomes (i.e., polyethyleneimine [PEI]-decorated liposomes) could enhance the clearance of PBUTs via electrostatic interactions. However, the poor biocompatibility (hemolysis) restricted their applications in clinical dialysis treatment. Herein, we produced PEI-anchored, linoleic acid-decorated liposomes (CP-LA liposomes) via the conjugation of PEI to cholesterol chloroformate (Chol-PEI, CP), and linoleic acid (LA) was added to provide liposomal colloidal stability. The CP-LA liposomes outperformed the plain liposomes, demonstrating significantly higher PBUT binding rates and removal rates. In addition, in vitro dialysis simulation verified that the CP-LA liposomes had a better capacity for PBUT clearance than the plain liposomes, especially for PBUTs with a strong negative net charge. Hemolysis and cytotoxicity tests revealed that the biocompatibility of the CP-LA liposomes was better than that of the physically-decorated PEI-liposome. CP-LA liposomes possess great potential for PBUT clearance in clinical dialysis therapy.
研究领域:
医学
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生物工程
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DOI
PubMed
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
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2025
·
IF 5.1
Lingyu Chen,Yunhong Liu,Xinyan Peng,Yuelan Wei,Ke Shao
Protein-bound uremic toxins (PBUTs) play a crucial role in the progression of uremic complications. Due to the extremely high binding affinity to human serum albumin, PBUTs are poorly removed by traditional hemodialysis methods. As an advanced blood purification technology, hemoperfusion has been proven effective in removing PBUTs, and hyper-crosslinked polystyrene adsorbents have been widely commercialized as hemoperfusion adsorption materials. However, challenges still remain, including the need to enhance the adsorption efficiency of PBUTs and the simplification of the preparation and modification processes of the adsorbents. In this work, we report a one-step external crosslinking modification technique to prepare a functionalized hyper-crosslinked polystyrene adsorbent named HCP-DFDA, in which N , N -dimethylformamide dimethyl acetal (DFDA) with tertiary amine functional groups was used as a small-molecule external crosslinker to simultaneously carry out Friedel–Crafts alkylation crosslinking and functional group grafting modification. Experimental results showed that the prepared hypercrosslinked resin HCP-DFDA had abundant mesoporous/microporous structures and an extremely high specific surface area of up to 1030 m 2 /g. Adsorption experiments demonstrated that HCP-DFDA exhibited excellent adsorption performance for both uremic PBUTs like indoxyl sulfate (IS) and p-cresyl sulfate (PCS) and medium- to large-molecular-weight toxins such as β2-microglobulin (β2-MG) and interleukin-6 (IL-6). Moreover, similar to the commercial HA130 resin, HCP-DFDA exhibited low protein adsorption and hemolysis rates, demonstrating good blood compatibility. In summary, the facile preparation method of the modified hypercrosslinked adsorbent proposed in this study provides a new idea and solution for the efficient removal of PBUTs through whole-blood hemoperfusion in clinical applications.
研究领域:
医学
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材料科学
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生物工程
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DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Haixin Zhao,Jia Huang,Lu Miao,Yuqi Yang,Zuoxiu Xiao,Qiaohui Chen,Qiong Huang,Kelong Ai
The high incidence of kidney disease caused by various factors (such as COVID-19) has triggered an extreme desire for wearable artificial kidney (WAK). Nevertheless, the dialysate regeneration system in WAK presents a very low adsorption capacity of urea, and must rely on the help of urease and zirconium compounds, which make the device too complex and costly, thus limiting their application. In this study, we employ the adsorption activity of defect-rich MoS 2 nanosheets with widened interlayer spacing (WDR-MoS 2 ) for the elimination of three crucial uremic toxins (urea, creatinine, and uric acid). The high adsorption performances of WDR-MoS 2 are owing to the presence of abundant S atoms between the two MoS 2 sheets that can efficiently adsorb uremic toxins through the unique S–N bond. Furthermore, widening the layer spacing of MoS 2 is similar to adjusting the aperture of a filter, which can not only speed up the transport of uremic toxins but also prevent the passage of large molecules (such as proteins). Thus, the WDR-MoS 2 can neither affect cell viability nor produce hemolysis and coagulation in the blood. Finally, a home-made WDR-MoS 2 fixed-bed system without urease and zirconium compounds is used to efficiently remove uremic toxins in the dialysate. WDR-MoS 2 is expected to fundamentally solve the materials science challenges in WAK and provide a new design idea for the development of high-performance 2D material-based adsorbents.
研究领域:
材料科学
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纳米技术
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生物医学工程
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DOI
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Liqin Wu,Xi Luo,Pengpeng Yue,Kalibinuer Yasen,Zibiao Zhong,Shuangquan Wu,Qifa Ye
The accumulation of uremic toxins, which ultimately leads to renal failure, results in systemic complications and necessitates efficient and biocompatible removal strategies. This paper presents the preparation of a biomimetic anisotropic aerogel composed of polyvinyl alcohol (PVA), sodium alginate (SA), and MXenes (Ti 3 C 2 T X ) via directional freezing. Inspired by plant vascular bundles, the resulting vertically aligned porous structure enhances the mechanical stability of and mass transfer in the material. The aerogel with its high MXene loading and high surface utilization offers remarkable adsorption capacities for urea (221.77 mg g −1 ) and creatinine (138.07 mg g −1 ). In vitro assays confirm the excellent hemo- and cytocompatibility of the aerogel. In a rabbit model of acute ischemic kidney injury, two-hour hemoperfusion with the aerogel significantly lowers the urea (38.67 to 16.17 mmol L −1 ) and creatinine levels (744.62 to 307.46 µmol L −1 ) without observable toxicity. The multidimensional biomimetic multipore anisotropic MXene aerogel presented here is a structurally optimized and biologically safe adsorbent for efficient uremic toxin clearance and a promising alternative to conventional hemodialysis.
研究领域:
生物材料
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肾病学
·
组织工程
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纳米医学
·
再生医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2022
·Vol. 57
·期 4
·2909-2923
·
IF 4.682
Zeng Sen,Hou Yaqi,Zhou Yaming,Zhou Xi,Ye Shefang,Wang Miao,Ren Lei
Protein-bound uremic toxins (PBUTs) are difficult to remove through dialytic procedures, and the accumulation of PBUTs is always associated with adverse symptoms in end-stage kidney disease. Hemoperfusions and novel membranes have been developed for the removal of PBUTs, but still suffer from low efficiency. Herein, we investigated the adsorption performance of three zirconium metal–organic frameworks (Zr-MOFs: UiO-66, UiO-66-SO 3 H, and UiO-66-(COOH) 2 ) for two typical PBUTs (indoxyl sulfate, IS; hippuric acid, HA). We found that Zr-MOFs could adsorb PBUTs efficiently with a capacity of as high as 49.5 mg g −1 for IS and 38.3 mg g −1 for HA, respectively, due to the van der Waals interactions, Coulomb interactions, and π – π interactions. Density functional theory simulations demonstrated that H-bonding on basis of the –SO 3 H and –COOH groups could endow MOFs with better absorptivity. Further, to expand to practical hemodialysis applications, we incorporated Zr-MOFs into a polylactide (PLA) matrix to fabricate MOFs-based mixed matrix membranes (MMMs). The MMMs showed excellent in vitro biocompatibility and high water flux up to 260 L m −2 h −1 . Under static conditions, the MMMs could remove HA and IS with a percentage of 75 and 78% in 4 h, respectively, whereas PLA membrane removed 12% of HA and 13% of IS. Under dynamic conditions, MMMs could remove 57% of IS and 54% of HA in 30 min; by contrast, PLA membrane only removed 2.9% of IS and 2.2% of HA. These MOFs-based MMMs with exceptional absorptivity, high water flux, and good biocompatibility might show great prospects in the foreground for the application of safe and efficient blood purification.
研究领域:
材料科学
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生物医学工程
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肾病学
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产品关联
DOI
高影响因子
BMC Nephrology
·
2019
·Vol. 20
·期 1
·1-7
·
IF 2.088
Xiong Ruifang,Lu Xiangxue,Song Jinghong,Li Han,Wang Shixiang
Background Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial.Methods 8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta.Results The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group).Conclusion Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.
研究领域:
心血管疾病
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分子生物学
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动物模型
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信号转导
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Yunhong Liu,Xinyan Peng,Zhudong Hu,Mingguang Yu,Jijun Fu,Yugang Huang
Protein-bound uremic toxins (PBUTs), the presence of which in the blood is an important risk factor for the progression of chronic kidney disease (CKD), have not been cleared efficiently via traditional hemodialysis methods until now. In this study, biosafe and efficient nitrogen-containing porous carbon adsorbent (NPCA) beads for the clearance of PBUTs were prepared from porous acrylonitrile/divinylbenzene cross-linked copolymer beads followed by pyrolysis. The resulting NPCA beads were characterized via SEM, XPS and nitrogen adsorption/desorption tests. The results demonstrated that the NPCA beads possessed a mesoporous/microporous hierarchical structure with rich nitrogen functional groups on their surfaces and realized efficient PBUTs adsorption in human plasma. More importantly, the efficacy of PBUTs removal was substantially higher than those of commercial adsorbents that are commonly used in clinical uremia treatments. The NPCA beads also exhibited satisfactory removal efficacy towards middle-molecular-weight uremic toxins. The PBUTs removal mechanism of the NPCA beads is ascribed to effective competition between nitrogen-containing NPCA and proteins for PBUT binding. According to hemocompatibility assays, the NPCA beads possessed satisfactory in vitro hemocompatibility. This nitrogen-containing porous carbon adsorbent is an attractive and promising material for blood purification applications in the treatment of clinical uremia.
研究领域:
材料科学
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生物医学工程
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肾病学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Hailin Liu,Xiuli Zhang,Xinglong Zhong,Zehua Li,Shaoai Cai,Pingzhen Yang,Caiwen Ou,Minsheng Chen
The risk of cardiovascular events in patients with chronic kidney disease is tremendously increased due to vascular calcification . Local vascular inflammation significantly promotes vascular calcification. A previous study has shown that puerarin inhibits calcification of mouse vascular smooth muscle cells (VSMCs) in vitro, but whether puerarin can inhibit vascular calcification in vivo and the underlying mechanisms remain unclear. In this study, we found that rat VSMCs treated with calcifying medium showed more mineral deposition, and this effect was inhibited by puerarin in a dose-dependent manner, as detected by alizarin red staining and calcium content assay. Puerarin also prevented the trans-differentiation of VSMCs into osteoblast-like cells, indicated by down-regulation of bone-related genes including Runx2 and BMP2 . In vivo study of uremic rats induced by renal nephrectomy further confirmed the inhibitory effect of puerarin on vascular calcification in uremic rats. Puerarin treatment significantly prevented mineral deposition in rat aortas and down-regulated the expression of Runx2 and BMP2. Furthermore, we detected the levels of pro-inflammatory cytokines including IL-1β, IL-6, IL-18 and TNFα in vitro and in vivo . The levels of IL-1β were remarkably increased in both calcified VSMCs and aortas of uremic rats, while puerarin treatment markedly decreased the expression of IL-1β. In addition, we found that puerarin reduced IL-1β possibly through targeting NLRP3/Caspase1/IL-1β and NF-κB signaling pathways and inhibiting the generation of reactive oxygen species . Taken together, we demonstrated that puerarin has the capability of inhibiting vascular calcification in uremic rats by inhibiting inflammation.
研究领域:
药理学
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心血管疾病
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肾脏疾病
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炎症
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）