Nanofiber-coated, tacrolimus-eluting sutures inhibit post-operative neointimal hyperplasia in rats

Kunal S. Parikh, Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Center for Bioengineering Innovation & Design, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Aditya Josyula, Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Takahiro Inoue, Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Takuma Fukunishi, Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Huaitao Zhang, Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Revaz Omiadze, Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Richard Shi, Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Youseph Yazdi, Center for Bioengineering Innovation & Design, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Justin Hanes, Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address: hanes@jhmi.edu.
Laura M. Ensign, Center for Nanomedicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD 21231, USA; Department of Gynecology and Obstetrics and Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: lensign@jhmi.edu.
Narutoshi Hibino, Advocate Aurora HealthFollow

Affiliations

Advocate Children's Hospital

Abstract

Post-operative complications of vascular anastomosis procedures remain a significant clinical challenge and health burden globally. Each year, millions of anastomosis procedures connect arteries and/or veins in vascular bypass, vascular access, organ transplant, and reconstructive surgeries, generally via suturing. Dysfunction of these anastomoses, primarily due to neointimal hyperplasia and the resulting narrowing of the vessel lumen, results in failure rates of up to 50% and billions of dollars in costs to the healthcare system. Non-absorbable sutures are the gold standard for vessel anastomosis; however, damage from the surgical procedure and closure itself causes an inflammatory cascade that leads to neointimal hyperplasia at the anastomosis site. Here, we demonstrate the development of a novel, scalable manufacturing system for fabrication of high strength sutures with nanofiber-based coatings composed of generally regarded as safe (GRAS) polymers and either sirolimus, tacrolimus, everolimus, or pimecrolimus. These sutures provided sufficient tensile strength for maintenance of the vascular anastomosis and sustained drug delivery at the site of the anastomosis. Tacrolimus-eluting sutures provided a significant reduction in neointimal hyperplasia in rats over a period of 14 days with similar vessel endothelialization in comparison to conventional nylon sutures. In contrast, systemically delivered tacrolimus caused significant weight loss and mortality due to toxicity. Thus, drug-eluting sutures provide a promising platform to improve the outcomes of vascular interventions without modifying the clinical workflow and without the risks associated with systemic drug delivery.

Document Type

Article

PubMed ID

36375620

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