Academic Journal
Macromolecular design of a bivalirudin peptide-loaded Carbopol 940 hydrogel for local thrombin inhibition and prevention of neointimal hyperplasia.
| Τίτλος: | Macromolecular design of a bivalirudin peptide-loaded Carbopol 940 hydrogel for local thrombin inhibition and prevention of neointimal hyperplasia. |
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| Συγγραφείς: | Huang TY; Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan; Division of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Keelung, 222 Mai-Chin Road, Keelung, 204, Taiwan. Electronic address: d07528011@gmail.com., Chiu WC; Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan., Liang YJ; Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan., Chen PY; Department of Neurosurgery, Chang Gung Memorial Hospital at Keelung, 222 Mai-Chin Road, Keelung, 204, Taiwan; School of Medicine, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Taoyuan City, 33302, Taiwan., Wang YC; Division of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Keelung, 222 Mai-Chin Road, Keelung, 204, Taiwan., Lin FH; Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd, Taipei, 10617, Taiwan; National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, 350, Taiwan. |
| Πηγή: | International journal of biological macromolecules [Int J Biol Macromol] 2026 Sep; Vol. 374, pp. 153323. Date of Electronic Publication: 2026 Jul 01. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: Guildford, Eng., IPC Science and Technology Press. |
| Ιατρικοί όροι (MeSH): | Hirudins*/chemistry , Hirudins*/pharmacology , Peptide Fragments*/chemistry , Peptide Fragments*/pharmacology , Hydrogels*/chemistry , Acrylic Resins*/chemistry , Neointima*/drug therapy , Neointima*/pathology , Neointima*/prevention & control , Neointima*/metabolism , Hyperplasia*/prevention & control , Thrombin*/antagonists & inhibitors , Thrombin*/metabolism , Antithrombins*/chemistry , Antithrombins*/pharmacology, Recombinant Proteins/chemistry ; Recombinant Proteins/pharmacology ; Cell Proliferation/drug effects ; Animals ; Humans ; Rats ; Male ; Drug Liberation ; Rats, Sprague-Dawley ; Cell Line |
| Περίληψη: | Neointimal hyperplasia (NIH) at vascular anastomosis sites remains a significant cause of graft failure after cardiovascular surgery. Here, we developed a bivalirudin-incorporated Carbopol 940 hydrogel (C-Biv) that provides sustained local thrombin inhibition, thereby preventing early thrombosis and subsequent smooth muscle proliferation. Bivalirudin is a 20-amino-acid thrombin-inhibiting peptide, and C-Biv was designed as a macromolecular network to modulate its local release and bioactivity at vascular anastomosis sites. Carbopol 940, a crosslinked polyacrylic acid, was selected for its high viscosity, pH-sensitive swelling, and established biocompatibility as a macromolecular carrier. Rheological characterization identified 0.5% (w/v) Carbopol 940 as the optimal formulation, achieving a viscosity comparable to that of medical lubricating gels (approximately 150 Pa·s). Drug-release analysis showed an initial burst of 60% bivalirudin within 24 h, followed by gradual release up to 72 h. The hydrogel exhibited excellent cytocompatibility (>90% cell viability in L929, A7r5, and HUVECs) and no measurable cytotoxicity as assessed by live/dead staining. In a rat abdominal aortic repair model, C-Biv application significantly reduced arterial wall thickening (showing a trend at 4 weeks: 373.4% in the PR group vs 152.6% in the C-Biv group, p = 0.0854; and a significant reduction at 12 weeks: 262.8% vs 126.9%, p = 0.0456) and decreased PCNA- and α-SMA-positive cell accumulation by over 40% at 4 and 12 weeks, without altering systemic biochemical parameters. These findings indicate that local delivery of bivalirudin via a biocompatible Carbopol 940 matrix effectively suppresses thrombin-mediated vascular remodeling, providing a practical and safe strategy for preventing postoperative vascular stenosis. (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper. |
| Contributed Indexing: | Keywords: Carbopol 940 hydrogel; bivalirudin peptide; neointimal hyperplasia |
| Substance Nomenclature: | 0 (Hirudins) TN9BEX005G (bivalirudin) 0 (Peptide Fragments) 0 (Recombinant Proteins) 0 (Hydrogels) 0 (Acrylic Resins) 4Q93RCW27E (carbopol 940) EC 3.4.21.5 (Thrombin) 0 (Antithrombins) |
| Entry Date(s): | Date Created: 20260701 Date Completed: 20260821 Latest Revision: 20260821 |
| Update Code: | 20260821 |
| DOI: | 10.1016/j.ijbiomac.2026.153323 |
| PMID: | 42385809 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1879-0003 |
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| DOI: | 10.1016/j.ijbiomac.2026.153323 |