Nitric oxide-generating self-assembling peptide hydrogel coating for enhancing hemocompatibility of blood-contacting devices

doi:10.1016/j.jmst.2022.05.025

J. Mater. Sci. Technol. ›› 2022, Vol. 131: 106-114.DOI: 10.1016/j.jmst.2022.05.025

• Research Article • Previous Articles Next Articles

Nitric oxide-generating self-assembling peptide hydrogel coating for enhancing hemocompatibility of blood-contacting devices

Hao Li^a^,^b, Qianru Guo^a, Qiufen Tu^a, Kaiqin Xiong, Wei Wang^d^,^*(), Lei Lu^e^,^f^,^*(), Wentai Zhang^b^,^g, Nan Huang^a, Zhilu Yang^a^,^b^,^g^,^*()

^aKey Laboratory of Advanced Technology for Materials of Education Ministry, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
^bAffiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523059, China
^cState Key Laboratory of Molecular Engineering of Polymers (Fudan University), Shanghai 200438, China
^dDepartment of Cardiology, Zigong First People's Hospital, Zigong 643000, China
^eSchool & Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325035, China
^fSichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China
^gGuangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou 510080, China

Received:2022-03-13 Revised:2022-04-25 Accepted:2022-05-10 Published:2022-06-09 Online:2022-06-09
Contact: Wei Wang,Lei Lu,Zhilu Yang
About author:zhiluyang1029@swjtu.edu.cn, zhiluyang1029@smu.edu.cn (Z. Yang)
llu2@foxmail.com (L. Lu),
*E-mail addresses: zgwangwei@163.com (W. Wang),
First author contact:
¹These authors contributed equally to this work.

Abstract

Abstract:

Thrombosis is the major stumbling block to the clinical application of blood-contacting devices. Herein, a quick and easy surface engineering strategy of hydrogel coating with the therapeutic gas nitric oxide (NO) generation was reported to realize up-regulation of cyclic guanosine monophosphate (cGMP) and improve hemocompatibility for diverse metal materials. We first introduce the active centre selenocysteine of glutathione peroxidase (GPx) to the self-assembling peptide (RADA)₄, obtaining a functionalized hydrogel. Then the hydrogel is directly coated on the 316L stainless steel (SS) for catalytically generating NO from endogenous s-nitrosothiols (RSNO). The generated NO endows the coated surface with regulation of platelet behavior and reduction of plasmatic coagulation activation and complement system activation, hence improving antithrombotic ability in vitro and ex vivo. Overall, our NO-generating hydrogel coating surface engineering strategy provides a novel solution to remove the obstacle about thrombosis of blood-contacting devices in clinic.

Key words: Blood-contacting device, NO generation, Self-assembling peptide, Hydrogel coating, Antithrombotic ability

Hao Li, Qianru Guo, Qiufen Tu, Kaiqin Xiong, Wei Wang, Lei Lu, Wentai Zhang, Nan Huang, Zhilu Yang. Nitric oxide-generating self-assembling peptide hydrogel coating for enhancing hemocompatibility of blood-contacting devices[J]. J. Mater. Sci. Technol., 2022, 131: 106-114.

Figures/Tables 5

Fig. 1. Construction of the hydrogel anticoagulant surface with the catalytic release of NO for regulation of the platelet aggregation and activation via NO-cGMP signaling pathway.

Fig. 2. Chemical structures of the self-assembling peptide (A-i) RADA and (A-ii) U. H NMR spectra of the self-assembling peptide (B-i) RADA and (B-ii) U. (C) Schematic of the hydrogel matrices with both RADA and U self-assembling peptides. (D-i) U&RADA peptide solution formed stable hydrogel after gelation. (D-ii) Congo red (CR) staining of the U&RADA hydrogel matrices. (D-iii) Circular dichroism (CD) spectroscopy of the peptide structure of the U&RADA hydrogel matrices.

Fig. 3. Characterization of U&RADA hydrogel coating. (A-i) Schematic of preparation of hydrogel coating. (A-ii) Photographs of the coating before and after coating. (A-iii) SEM images of U&RADA hydrogel coating. (B) GATR-FTIR spectrum of U&RADA hydrogel coating. (C) XPS wide-scan survey spectra of the U&RADA, RADA hydrogel coating and 316L SS substrate, and (D) high-resolution spectra of Se 3d in U&RADA and RADA hydrogel coatings. (E) Thickness of the hydrogel coatings. (F) Real-time release of NO catalyzed by the hydrogel coating. (G) NO catalytic release rates of different surfaces. Data presented as mean ± SD (n = 4) and analyzed by one-way ANOVA (***p < 0.001).

Fig. 4. In vitro anticoagulant and anti-complement system activation ability of the hydrogel coating. (A) cGMP expression of the platelets adhered to the coating. (B) SEM images of the adherent platelets and relative quantification of (C) the count of adherent platelets and (D) the ratio of activated platelets. (E) Hemolysis rate of the coating. (F) Concentration of F1 + 2, PF4, CRP and C5a in the whole blood incubated with the coating in vitro. “U&RADA (+/-)” represented the group treated with or without the supplement of NO donor. Data were presented as mean ± SD (n = 4) and analyzed by one-way ANOVA (* compared with 316L SS, # compared with RADA, & compared with U&RADA (-); *p < 0.05, **p < 0.01, ***p < 0.001).

Fig. 5. Ex vivo hemocompatibility evaluation for the hydrogel coating. (A) Schematic of the rabbit arteriovenous extracorporeal circuit model. (B) Cross-sectional photographs of thrombi forming on the catheter inserted with samples. Quantitative analysis of (C) occlusion rate and (D) blood flow rate of the catheter containing formed thrombi. (E) Photographs, (F) thrombus weight statistic and (G) SEM images of the thrombi on the surface of coated and uncoated substrates. Data were presented as mean ± SD (n = 4) and analyzed by one-way ANOVA (* compared with 316L SS, # compared with RADA, *p < 0.05, **p < 0.01, ***p < 0.001).

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Nitric oxide-generating self-assembling peptide hydrogel coating for enhancing hemocompatibility of blood-contacting devices

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