A synergistic strategy of dual-crosslinking and loading intelligent nanogels for enhancing anti-coagulation, pro-endothelialization and anti-calcification properties in bioprosthetic heart valves
Source abstract
Abstract
Currently, glutaraldehyde (GA)-crosslinked bioprosthetic heart valves (BHVs) still do not guarantee good biocompatibility and long-term effective durability for clinical application due to their subacute thrombus, inflammation, calcification, tearing and limited durability. In this study, double-modified xanthan gum (oxidized/vinylated xanthan gum (O2CXG)) was acquired from xanthan gum for subsequent double crosslinking and modification platform construction. Sulfonic acid groups with anticoagulant properties were also introduced through the free radical polymerization of vinyl sulfonate (VS) and vinyl on O2CXG. Taking advantage of the drug-loading function of xanthan gum, the treated pericardium was further loaded with inflammation-triggered dual drug-loaded nanogel (heparin (Hep) and atorvastatin (Ator)). Mechanical properties of O2CXG-crosslinked porcine pericardium (O2CXG-PP) were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Due to the presence of sulfonic acid groups as well as the dual drug release from nanogels under the stimulation of H2O2, the hemocompatibility, anti-inflammatory, pro-endothelialization and anti-calcification properties of the crosslinked pericardium modified with nanogels loaded with Hep and Ator (O2CXG+VS+(Hep+Ator) nanogel-PP) was significantly better than that of GA-crosslinked PP (GA-PP). The collaborative strategy of double crosslinking and sequential release of anticoagulant/endothelium-promoting drugs triggered by inflammation could effectively meet the requirement of enhanced multiple performance and long-term durability of bioprosthetic heart valves and provide a valuable pattern for multi-functionalization of blood contacting materials. STATEMENT OF SIGNIFICANCE: Currently, glutaraldehyde-crosslinked bioprosthetic heart valves (BHVs) are subject to subacute thrombus, inflammation, calcification and tearing, which would not guarantee good biocompatibility and long-term effective durability. We developed a cooperative strategy of double crosslinking and surface modification in which double-modified xanthan gum plays a cornerstone. The mechanical properties of this BHV were significantly improved via the first network formed by Schiff base bonds and the second C-C bonds network. Inflammation-triggered combination delivery of heparin and atorvastatin has been demonstrated to enhance anticoagulation, anti-inflammatory and pro-endothelialization of BHVs by utilizing local inflammatory response. The collaborative strategy could effectively meet the requirement of enhanced multiple performance and long-term durability of BHVs and provide a valuable pattern for the multi-functionalization of blood-contacting materials.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Cardiac Valve Diseases and Treatments · Cardiac and Coronary Surgery Techniques · Aortic Disease and Treatment Approaches
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (69)
Show source-provided references
1. Development of innovative biomaterials and devices for the treatment of cardiovascular diseases
2. Letter by Koh regarding article,“Dipeptidyl peptidase-4 induces aortic valve calcification by inhibiting insulin-like growth factor-1 signaling in valvular interstitial cells10.1161/CIRCULATIONAHA.117.029815 ↗
3. A novel crosslinking method for improved tear resistance and biocompatibility of tissue based biomaterials10.1016/j.biomaterials.2015.07.011 ↗
4. R.P. Whitlock, J.W. Eikelboom, Prevention of thromboembolic events after bioprosthetic aortic valve replacement: what is the optimal antithrombotic strategy?, American College of Cardiology Foundation Washington, DC, 2012, pp. 978-980.10.1016/j.jacc.2012.06.014 ↗
5. M. Szerlip, Transcatheter aortic valve replacement: only one of the advantages of being female, American College of Cardiology Foundation Washington, DC, 2016, pp. 2745-2746.10.1016/j.jacc.2016.10.042 ↗
6. Transcatheter aortic valve replacement in bicuspid aortic valve stenosis10.1161/CIRCULATIONAHA.120.048048 ↗
7. Evolving indications of transcatheter aortic valve replacement—where are we now, and where are we going10.3390/jcm11113090 ↗
8. Optimizing glutaraldehyde-fixed tissue heart valves with chondroitin sulfate hydrogel for endothelialization and shielding against deterioration10.1021/acs.biomac.8b00077 ↗
9. Bioprosthetic heart valve heterograft biomaterials: structure, mechanical behavior and computational simulation10.1586/17434440.3.6.817 ↗
10. The effect of decellularisation on the real time mechanical fatigue of porcine aortic heart valve roots10.1371/journal.pone.0265763 ↗
11. Bioprosthetic valve thrombosis10.1016/j.jacc.2017.02.051 ↗
12. Neutrophil extracellular traps induce platelet adhesion and thrombus formation
13. Incidence, timing, and predictors of valve hemodynamic deterioration after transcatheter aortic valve replacement: multicenter registry10.1016/j.jacc.2015.10.097 ↗
14. Impact of anticoagulation therapy on valve haemodynamic deterioration following transcatheter aortic valve replacement10.1136/heartjnl-2017-312514 ↗
15. Quercetin-crosslinked porcine heart valve matrix: mechanical properties, stability, anticalcification and cytocompatibility10.1016/j.actbio.2009.07.035 ↗
16. On the biomechanical role of glycosaminoglycans in the aortic heart valve leaflet10.1016/j.actbio.2012.09.031 ↗
17. Neomycin and pentagalloyl glucose enhanced cross-linking for elastin and glycosaminoglycans preservation in bioprosthetic heart valves10.1177/0885328213479047 ↗
18. Biomechanical behavior of bioprosthetic heart valve heterograft tissues: Characterization, simulation, and performance10.1007/s13239-016-0276-8 ↗
19. Freezing–thawing effects on the properties of dialdehyde carboxymethyl cellulose crosslinked gelatin-MMT composite films10.1016/j.foodhyd.2013.04.004 ↗
20. Preparation and properties of dialdehyde carboxymethyl cellulose crosslinked gelatin edible films10.1016/j.foodhyd.2011.09.005 ↗
21. Dialdehyde pectin-crosslinked and hirudin-loaded decellularized porcine pericardium with improved matrix stability, enhanced anti-calcification and anticoagulant for bioprosthetic heart valves10.1039/D1BM01297E ↗
22. Dialdehyde xanthan gum and curcumin synergistically crosslinked bioprosthetic valve leaflets with anti-thrombotic, anti-inflammatory and anti-calcification properties10.1016/j.carbpol.2023.120724 ↗
23. Crosslinking of decellularized porcine heart valve matrix by procyanidins10.1016/j.biomaterials.2006.02.008 ↗
24. Radical polymerization-crosslinking method for improving extracellular matrix stability in bioprosthetic heart valves with reduced potential for calcification and inflammatory response10.1016/j.actbio.2018.10.017 ↗
25. A method for simultaneously crosslinking and functionalizing extracellular matrix-based biomaterials as bioprosthetic heart valves with enhanced endothelialization and reduced inflammation10.1016/j.actbio.2020.10.029 ↗
26. Type 2 diabetes mellitus is associated with faster degeneration of bioprosthetic valve: results from a propensity Score–Matched Italian multicenter study10.1161/CIRCULATIONAHA.111.025064 ↗
27. Degeneration of bioprosthetic heart valves: update 202010.1161/JAHA.120.018506 ↗
28. Lipid-mediated inflammation and degeneration of bioprosthetic heart valves10.1111/j.1365-2362.2009.02132.x ↗
29. Oxidant generation predominates around calcifying foci and enhances progression of aortic valve calcification10.1161/ATVBAHA.107.156745 ↗
30. Boronate-based fluorescent probes for imaging cellular hydrogen peroxide10.1021/ja054474f ↗
31. Recognition and sensing of various species using boronic acid derivatives10.1039/c2cc31985c ↗
32. Inflammation-responsive drug-conjugated dextran nanoparticles enhance anti-inflammatory drug efficacy10.1021/acsami.8b08254 ↗
33. Xanthan gum hydrogels as high-capacity adsorbents for dye removal10.1021/acsapm.1c00343 ↗
34. An experimental toolbox for characterization of mammalian collagen type I in biological specimens10.1038/nprot.2017.117 ↗
35. Feasibility study of oxidized hyaluronic acid cross-linking acellular bovine pericardium with potential application for abdominal wall repair10.1016/j.ijbiomac.2021.06.113 ↗
36. Self-crosslinking and injectable hyaluronic acid/RGD-functionalized pectin hydrogel for cartilage tissue engineering10.1016/j.carbpol.2017.02.059 ↗
37. Well-designed two-fold crosslinked biological valve leaflets with heparin-loaded hydrogel coating for enhancing anticoagulation, endothelialization, and anticalcification10.1039/D2BM00736C ↗
38. ROS-responsive nano-drug delivery system combining mitochondria-targeting ceria nanoparticles with atorvastatin for acute kidney injury10.7150/thno.40395 ↗
39. Atorvastatin loaded PLGA microspheres: Preparation, HAp coating, drug release and effect on osteogenic differentiation of ADMSCs10.1016/j.ijpharm.2019.05.005 ↗
40. Isolation and characterization of primary rat valve interstitial cells: A new model to study aortic valve calcification
41. Self-crosslinked chitosan/dialdehyde xanthan gum blended hypromellose hydrogel for the controlled delivery of ampicillin, minocycline and rifampicin10.1016/j.ijbiomac.2020.11.100 ↗
42. Preparation and antioxidant activity of xanthan oligosaccharides derivatives with similar substituting degrees10.1016/j.foodchem.2014.05.001 ↗
43. Smart and regeneratable Xanthan gum hydrogel adsorbents for selective removal of cationic dyes10.1016/j.jece.2022.107620 ↗
44. Photochemical behavior of the drug atorvastatin in water10.1016/j.tet.2006.05.027 ↗
45. A multi-in-one strategy with glucose-triggered long-term antithrombogenicity and sequentially enhanced endothelialization for biological valve leaflets10.1016/j.biomaterials.2021.120981 ↗
46. Applications of highly salt and highly temperature resistance terpolymer of acrylamide/styrene/maleic anhydride monomers as a rheological modifier: Rheological and corrosion protection properties studies10.1016/j.molliq.2019.111635 ↗
47. Adsorption of trifluoromethane sulfonic acid on Pt by FTIR and radiotracer methods10.1149/1.2115323 ↗
48. Surface modification of commercial polyamide reverse osmosis membranes by radical grafting: An ATR-FTIR study10.1002/(SICI)1521-4044(199810)49:10/11<574::AID-APOL574>3.0.CO;2-0 ↗
49. A pH, glucose, and dopamine triple-responsive, self-healable adhesive hydrogel formed by phenylborate–catechol complexation10.1039/C7PY00519A ↗
50. Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing10.1016/j.bioactmat.2022.01.004 ↗
51. Evaluation of transcatheter heart valve biomaterials: biomechanical characterization of bovine and porcine pericardium10.1016/j.jmbbm.2017.08.013 ↗
52. Cross-linking porcine pericardium by 3, 4-dihydroxybenzaldehyde: a novel method to improve the biocompatibility of bioprosthetic valve10.1021/acs.biomac.0c01554 ↗
53. Single and multi-functional coating strategies for enhancing the biocompatibility and tissue integration of blood-contacting medical implants10.1016/j.biomaterials.2020.120291 ↗
54. Sodium lignosulfonate cross-linked bioprosthetic heart valve materials for enhanced cytocompatibility, improved hemocompatibility, and reduced calcification10.1016/j.compositesb.2022.109669 ↗
55. Neomycin and carbodiimide crosslinking as an alternative to glutaraldehyde for enhanced durability of bioprosthetic heart valves10.1177/0885328211430542 ↗
56. Enhanced blood compatibility of polymers grafted by sulfonated PEO via a negative cilia concept10.1016/S0142-9612(03)00023-1 ↗
57. A bioprosthetic heart valve prepared by copolymerization of 2-isocyanatoethyl methacrylate modified pericardium and functional monomer10.1016/j.compositesb.2022.109922 ↗
58. A bioprosthetic heart valve material prepared by copolymerization of 2-Amino-4-pentanoic acid modified pericardium and N, N-Dimethylacrylamide10.1016/j.compositesb.2022.110120 ↗
59. Study on the potential mechanism of anti-inflammatory activity of covalently immobilized hyaluronan and heparin10.1002/jbm.a.36885 ↗
60. Cell biology of valvular interstitial cells
61. Phenotypic and functional characterization of interstitial cells from human heart valves, pericardium and skin
62. Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves
63. Characterization of cell motility in single heart valve interstitial cells in vitro
64. Transforming growth factor-β regulates in vitro heart valve repair by activated valve interstitial cells10.2353/ajpath.2008.080365 ↗
65. The influence of heart valve leaflet matrix characteristics on the interaction between human mesenchymal stem cells and decellularized scaffolds10.1016/j.biomaterials.2009.04.031 ↗
66. Species-specific effects of aortic valve decellularization10.1016/j.actbio.2017.01.008 ↗
67. Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy10.1002/jcp.27442 ↗
68. Strategies for development of decellularized heart valve scaffolds for tissue engineering10.1016/j.biomaterials.2022.121675 ↗
69. Tissue engineering at the blood-contacting surface: a review of challenges and strategies in vascular graft development10.1002/adhm.201701461 ↗