CoChat
Sign Up
Cited by 3Tissue Engineering and Regenerative MedicineElectrospun Nanofibers in Biomedical ApplicationsNitric Oxide and Endothelin Effects

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Bilayer vascular grafts separately loaded with sodium copper chlorophyllin and keratin-based hydrogen sulfide donor with pro-endothelialization, anti-thrombogenicity, anti-inflammation, and anti-calcification properties

Open access
Sun, Yu, Hu, Shunqi, Wang, Lijuan, Liang, Fubang, Zhou, Zeyi, Zhang, Yuyuan, Pan, Yanjun, Shen, Jian, Yin, Meng, Yuan, Jiang·2026·Bioactive Materials
DOI 10.1016/j.bioactmat.2025.11.001PMC PMC12661995
Open this paper in CoChat — free account

Abstract

The clinical utility of small-diameter vascular grafts (SDVGs) remains limited due to thrombosis, inflammation, and intimal hyperplasia, which compromise long-term patency. Mimicking the structures and functions of blood vessels, bilayer SDVGs with gradient pore sizes were fabricated, thereby preventing the infiltration of vascular smooth muscle cells (VSMCs) into the inner layer. Additionally, sodium copper chlorophyllin (SCC) was embedded in the inner layer, potentially generating NO from endogenous donors in the blood and regulating vascular cells. Keratin-based H2S donor of KSN was synthesized and then electrospun with poly(L-lactide-co-ε-caprolactone) (PLCL) to serve as the outer layer of the grafts. The bilayer grafts promoted rapid endothelialization by selectively enhancing the adhesion, proliferation, and migration of vascular endothelial cells (VECs) while inhibiting those of VSMCs. More importantly, the released NO and H2S synergistically enhanced the anti-thrombotic, anti-inflammatory, and anti-calcification properties of the grafts. Furthermore, the bilayer grafts maintained the contractile phenotype of VSMCs and polarized macrophages toward the M2 phenotype. The grafts achieved patency with negligible intimal hyperplasia and calcification in the rat abdominal aorta replacement models for 1 month of implantation. The grafts modulated VECs via the VEGF, PI3K-AKT, and focal adhesion signaling pathways, while regulating VSMCs through cell cycle, PI3K-Akt, MAPK, and Hippo signaling pathways, as well as ECM-receptor interaction. These bilayer grafts with rapid endothelialization, antithrombogenicity, anti-inflammation, and anti-calcification properties are promising candidates for tissue-engineered SDVGs.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.bioactmat.2025.11.001

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • PLCL applications include wound healing, vascular transplantation, bone and cartilage repair, and drug delivery systems.

    “These applications include wound healing, vascular transplantation, bone and cartilage repair, and even drug delivery systems [14–20].”

    From Application of PLCL as a biodegradable polymer in biomedical engineering (2026) · cites this paper as [20]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 64

  1. L'Heureux, 2007, Technology insight: the evolution of tissue-engineered vascular grafts--from research to clinical practice, Nat. Clin. Pract. Cardiovasc. Med., 4, 389, 10.1038/ncpcardio0930 · DOI
  2. Gong, 2016, Hybrid small-diameter vascular grafts: Anti-expansion effect of electrospun poly epsilon-caprolactone on heparin-coated decellularized matrices, Biomaterials, 76, 359, 10.1016/j.biomaterials.2015.10.066 · DOI
  3. Gupta, 2021, Tissue‐engineered vascular grafts: emerging trends and technologies, Adv. Funct. Mater., 31, 10.1002/adfm.202100027 · DOI
  4. Ross, 1999, Atherosclerosis--an inflammatory disease, N. Engl. J. Med., 340, 115, 10.1056/NEJM199901143400207 · DOI · Paper page
  5. Chen, 2023, Phenotypic switching of vascular smooth muscle cells in atherosclerosis, J. Am. Heart Assoc., 12, 10.1161/JAHA.123.031121 · DOI
  6. Duque, 2017, Dialysis arteriovenous fistula failure and angioplasty: intimal hyperplasia and other causes of access failure, Am. J. Kidney Dis., 69, 147, 10.1053/j.ajkd.2016.08.025 · DOI
  7. Wu, 2019, The cholesteryl ester transfer protein inhibitor, des-Fluoro-Anacetrapib, prevents vein bypass-induced neointimal hyperplasia in New Zealand white rabbits, Sci. Rep., 9
  8. Ma, 2023, Peptide vaccine against ADAMTS-7 ameliorates atherosclerosis and postinjury neointima hyperplasia, Circulation, 147, 728, 10.1161/CIRCULATIONAHA.122.061516 · DOI
  9. Kochová, 2009, Aorta remodelling associated with calcitonin gene related peptide concentration in rats with arterial hypertension, Acta Vet. Brno, 78, 595, 10.2754/avb200978040595 · DOI
  10. Hammes, 2015, Hemodynamic and biologic determinates of arteriovenous fistula outcomes in renal failure patients, BioMed Res. Int., 2015, 10.1155/2015/171674 · DOI
  11. Sassi, 2017, PDF-ECG in clinical practice: a model for long-term preservation of digital 12-lead ECG data, J. Electrocardiol., 50, 776, 10.1016/j.jelectrocard.2017.08.001 · DOI
  12. Wang, 2015, The role of H2S bioavailability in endothelial dysfunction, Trends Pharmacol. Sci., 36, 568, 10.1016/j.tips.2015.05.007 · DOI
  13. Yuan, 2017, Beyond a gasotransmitter: hydrogen sulfide and polysulfide in cardiovascular health and immune response, Antioxidants Redox Signal., 27, 634, 10.1089/ars.2017.7096 · DOI
  14. Hosoki, 1997, The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide, Biochem. Biophys. Res. Commun., 237, 527, 10.1006/bbrc.1997.6878 · DOI
  15. Leal, 2020, Vascular tissue engineering: polymers and methodologies for small caliber vascular grafts, Front. Cardiovasc. Med., 7
  16. Chong, 2019, Simultaneous determination of sodium iron chlorophyllin and sodium copper chlorophyllin in food using high-performance liquid chromatography and ultra-performance liquid chromatography-mass spectrometry, Food Chem., 276, 390, 10.1016/j.foodchem.2018.10.015 · DOI
  17. Patar, 2018, Chlorophyllin supplementation modulates hyperglycemia-induced oxidative stress and apoptosis in liver of streptozotocin-administered mice, Biofactors, 44, 418, 10.1002/biof.1438 · DOI
  18. Luo, 2015, Copper-incorporated collagen/catechol film for in situ generation of nitric oxide, ACS Biomater. Sci. Eng., 1, 771, 10.1021/acsbiomaterials.5b00131 · DOI
  19. Darder, 2020, Cellulose-based biomaterials integrated with copper-cystine hybrid structures as catalysts for nitric oxide generation, Mater. Sci. Eng. C Mater. Biol. Appl., 108, 10.1016/j.msec.2019.110369 · DOI
  20. Han, 2022, Hydrogen sulfide-releasing polyurethane/gelatin/keratin-TA conjugate mats for wound healing, J. Mater. Chem. B, 10, 8672, 10.1039/D2TB01700H · DOI
  21. Klein, 2017, Hemodynamic influence on smooth muscle cell kinetics and phenotype during early vein graft adaptation, Ann. Biomed. Eng., 45, 644, 10.1007/s10439-016-1725-0 · DOI
  22. Szabo, 2017, Hydrogen sulfide, an enhancer of vascular nitric oxide signaling: mechanisms and implications, Am. J. Physiol. Cell Physiol., 312, C3, 10.1152/ajpcell.00282.2016 · DOI
  23. Donnarumma, 2016, Nitrite therapy ameliorates myocardial dysfunction via H2S and nuclear factor-erythroid 2-Related factor 2 (Nrf2)-Dependent signaling in chronic heart failure, J. Am. Heart Assoc., 5, 10.1161/JAHA.116.003551 · DOI
  24. Liu, 2023, Multifunctional antibiotics-free hydrogel dressings with self-regulated nitric oxide-releasing kinetics for improving open wound healing, J. Mater. Chem. B, 11, 3650, 10.1039/D2TB02671F · DOI
  25. Su, 2023, Cellular energy supply for promoting vascular remodeling of small-diameter vascular grafts: a preliminary study of a new strategy for vascular graft development, Biomater. Sci., 11, 3197, 10.1039/D2BM01338J · DOI
  26. Liu, 2023, Evaluation of mechanical properties and biocompatibility of three-layer PCL/PLLA small-diameter vascular graft with pore diameter gradient, Eur. Polym. J., 186, 10.1016/j.eurpolymj.2023.111864 · DOI
  27. Valanti, 2022, Reconstituted HDL-apoE3 promotes endothelial cell migration through ID1 and its downstream kinases ERK1/2, AKT and p38 MAPK, Metabolism, 127, 10.1016/j.metabol.2021.154954 · DOI
  28. Cheng, 2017, Cancer cells increase endothelial cell tube formation and survival by activating the PI3K/Akt signalling pathway, J. Exp. Clin. Cancer Res., 36, 27, 10.1186/s13046-017-0495-3 · DOI
  29. Shu, 2024, MG-132 activates sodium palmitate-induced autophagy in human vascular smooth muscle cells and inhibits senescence via the PI3K/AKT/mTOR axis, Lipids Health Dis., 23, 282, 10.1186/s12944-024-02268-w · DOI
  30. Forman, 2021, Targeting oxidative stress in disease: promise and limitations of antioxidant therapy, Nat. Rev. Drug Discov., 20, 689, 10.1038/s41573-021-00233-1 · DOI · Paper page
  31. Zhan, 2014, In vitro antioxidant activities of sodium zinc and sodium iron chlorophyllins from pine needles, Food Technol. Biotechnol., 52, 505, 10.17113/ftb.52.04.14.3592 · DOI
  32. Silvestre-Roig, 2014, Atherosclerotic plaque destabilization: mechanisms, models, and therapeutic strategies, Circ. Res., 114, 214, 10.1161/CIRCRESAHA.114.302355 · DOI
  33. Kalantzopoulos, 2018, In situ flow MAS NMR spectroscopy and synchrotron PDF analyses of the local response of the bronsted acidic site in SAPO-34 during hydration at elevated temperatures, ChemPhysChem, 19, 519, 10.1002/cphc.201700973 · DOI
  34. Burton, 2010, Pathophysiology of vascular calcification: pivotal role of cellular senescence in vascular smooth muscle cells, Exp. Gerontol., 45, 819, 10.1016/j.exger.2010.07.005 · DOI · Paper page
  35. Majumdar, 2021, Nitric oxide prevents aortic valve calcification by S-nitrosylation of USP9X to activate NOTCH signaling, Sci. Adv., 7, 10.1126/sciadv.abe3706 · DOI
  36. Combi, 2023, Hydrogen sulfide as an anti-calcification stratagem in human aortic valve: altered biogenesis and mitochondrial metabolism of H2S lead to H2S deficiency in calcific aortic valve disease, Redox Biol., 60, 10.1016/j.redox.2023.102629 · DOI
  37. Wang, 2021, Hydrogen sulfide prevents arterial medial calcification in rats with diabetic nephropathy, BMC Cardiovasc. Disord., 21, 495, 10.1186/s12872-021-02307-9 · DOI
  38. Jia, 2022, Construction of enzyme-laden vascular scaffolds based on hyaluronic acid oligosaccharides-modified collagen nanofibers for antithrombosis and in-situ endothelialization of tissue-engineered blood vessels, Acta Biomater., 153, 287, 10.1016/j.actbio.2022.09.041 · DOI
  39. Damodaran, 2013, Anti-thrombogenic properties of a nitric oxide-releasing dextran derivative: evaluation of platelet activation and whole blood clotting kinetics, RSC Adv., 3, 10.1039/c3ra45521a · DOI
  40. Bolotina, 1994, Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle, Nature, 368, 850, 10.1038/368850a0 · DOI
  41. Yang, 2019, Hybrid electrospun rapamycin-loaded small-diameter decellularized vascular grafts effectively inhibit intimal hyperplasia, Acta Biomater., 97, 321, 10.1016/j.actbio.2019.06.037 · DOI
  42. Blit, 2011, Platelet inhibition and endothelial cell adhesion on elastin-like polypeptide surface modified materials, Biomaterials, 32, 5790, 10.1016/j.biomaterials.2011.04.067 · DOI
  43. Chen, 2023, Two-pronged microbe delivery of nitric oxide and oxygen for diabetic wound healing, Nano Lett., 23, 5595, 10.1021/acs.nanolett.3c01023 · DOI
  44. Midgley, 2020, Nitric-oxide-releasing biomaterial regulation of the stem cell microenvironment in regenerative medicine, Adv. Mater., 32, 10.1002/adma.201805818 · DOI
  45. Corvino, 2021, Trends in H2S-Donors chemistry and their effects in cardiovascular diseases, Antioxidants (Basel), 10, 429, 10.3390/antiox10030429 · DOI
  46. Wang, 2025, Bilayer vascular grafts separately composited with nitric oxide-releasing keratin conjugates and hydrogen sulfide-releasing heparin conjugates, Int. J. Biol. Macromol., 307
  47. Li, 2024, Bilayer vascular grafts with on-demand NO and H2S release capabilities, Bioact. Mater., 31, 38
  48. Wang, 2024, Endothelium-mimicking bilayer vascular grafts with dual-releasing of NO/H2S for anti-inflammation and anticalcification, ACS Appl. Mater. Interfaces, 16, 318, 10.1021/acsami.3c15176 · DOI
  49. Li, 2021, Nitric oxide-releasing poly(epsilon-caprolactone)/S-nitrosylated keratin biocomposite scaffolds for potential small-diameter vascular grafts, Int. J. Biol. Macromol., 189, 516, 10.1016/j.ijbiomac.2021.08.147 · DOI
  50. Wu, 2018, Novel H(2)S-NO hybrid molecule (ZYZ-803) promoted synergistic effects against heart failure, Redox Biol., 15, 243, 10.1016/j.redox.2017.11.020 · DOI
  51. Shvetsova, 2021, Intrauterine nitric oxide deficiency weakens differentiation of vascular smooth muscle in newborn rats, Int. J. Mol. Sci., 22, 8003, 10.3390/ijms22158003 · DOI
  52. Li, 2017, Hydrogen sulfide facilitates the impaired sensitivity of carotid sinus baroreflex in rats with vascular calcification, Front. Pharmacol., 8, 10.3389/fphar.2017.00629 · DOI
  53. Liu, 2023, The influence of textile structure characteristics on the performance of artificial blood vessels, Polymers, 15, 3003, 10.3390/polym15143003 · DOI
  54. Fu, 2025, 3D micro-nano hierarchical constructs enabling transmural ingrowth of adventitia improves the “Fallout endothelialization”of vascular grafts, Adv. Funct. Mater., 35, 10.1002/adfm.202416702 · DOI
  55. de Valence, 2012, Long term performance of polycaprolactone vascular grafts in a rat abdominal aorta replacement model, Biomaterials, 33, 38, 10.1016/j.biomaterials.2011.09.024 · DOI
  56. Leopold, 2015, Vascular calcification: mechanisms of vascular smooth muscle cell calcification, trends cardiovasc, Med., 25, 267
  57. Voelkl, 2019, Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia, Cell. Mol. Life Sci., 76, 2077
  58. Lee, 2020, Vascular calcification-new insights into its mechanism, Int. J. Mol. Sci., 21, 2685, 10.3390/ijms21082685 · DOI
  59. Shi, 2023, Biomimetic tri-layered small-diameter vascular grafts with decellularized extracellular matrix promoting vascular regeneration and inhibiting thrombosis with the salidroside, Mater. Today Bio, 21
  60. Li, 2019, Bilayered polymeric Micro- and nanofiber vascular grafts as abdominal aorta replacements: long-term in vivo studies in a rat model, ACS Appl. Bio Mater., 2, 4493, 10.1021/acsabm.9b00641 · DOI
  61. Matsuzaki, 2020, The effect of pore diameter on neo-tissue formation in electrospun biodegradable tissue-engineered arterial grafts in a large animal model, Acta Biomater., 115, 176, 10.1016/j.actbio.2020.08.011 · DOI
  62. Feng, 2020, Influence of pore architectures of silk fibroin/collagen composite scaffolds on the regeneration of osteochondral defects in vivo, J. Mater. Chem. B, 8, 391, 10.1039/C9TB01558B · DOI · Paper page
  63. Wang, 2024, Endothelium-mimicking bilayer vascular grafts with dual-releasing of NO/H2S for anti-inflammation and anticalcification, ACS Appl. Mater. Interfaces, 318, 10.1021/acsami.3c15176 · DOI
  64. Kleinman, 2000, Status of glutathione and other thiols and disulfides in human plasma, Biochem. Pharmacol., 60, 19, 10.1016/S0006-2952(00)00293-8 · DOI

Cited by

Sorted by citations

Metadata

Authors
Sun, Y., Hu, S., Wang, L., Liang, F., Zhou, Z., Zhang, Y., Pan, Y., Shen, J., Yin, M., & Yuan, J.
Affiliations
  • Nanjing Normal University (CN)
  • Shanghai Jiao Tong University (CN)
  • Nanjing Drum Tower Hospital (CN)
  • Xi’an Jiaotong-Liverpool University (CN)
Corresponding author
  • Yin, Meng
  • Yuan, Jiang
ORCID
Venue
Bioactive Materials
Publisher
Elsevier BV
Published
2026-03
Volume
57
Pages
247-266
ISSN
  • 2097-1192 (ISSN-L)
  • 2452-199X
DOI
10.1016/j.bioactmat.2025.11.001
PMC
PMC12661995
OpenAlex
W4416267771
Cited by
3
References
2
Citations by year
2026: 3
FWCI
2.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioactive Materials (publishedVersion, cc-by)
  • SSRN Electronic Journal (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions (19KJA150001)
  • Priority Academic Program Development of Jiangsu Higher Education Institutions
  • Foundation of Jiangsu Collaborative Innovation Center of Biomedical Functional Materials
  • National Natural Science Foundation of China (81873923, 82200527)
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
  • Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords
small-diameter vascular grafts, sodium copper chlorophyllin, hydrogen sulfide, nitric oxide, endothelialization, intimal hyperplasia, vascular calcification, thrombogenicity, inflammation, vascular smooth muscle cells, macrophage polarization, PI3K/Akt signaling, electrospinning, poly(L-lactide-co-ε-caprolactone), tissue-engineered vascular grafts

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review