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

Kunal S Parikh; Aditya Josyula; Takahiro Inoue; Takuma Fukunishi; Huaitao Zhang; Revaz Omiadze; Richard Shi; Youseph Yazdi; Justin Hanes; Laura M Ensign; Narutoshi Hibino

doi:10.1016/j.jconrel.2022.11.020

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

J Control Release. 2023 Jan:353:96-104. doi: 10.1016/j.jconrel.2022.11.020. Epub 2022 Nov 23.

Authors

Affiliations

¹ 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.
² 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.
³ Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ 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: [email protected].
⁸ 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: [email protected].
⁹ Department of Cardiac Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Department of Cardiac Surgery, University of Chicago/Advocate Children's Hospital, Chicago, IL 60637, USA. Electronic address: [email protected].

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.

Keywords: Anastomosis; Anti-proliferative; Nanofiber; Suture; Tacrolimus; Vascular.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Hyperplasia / prevention & control
Nanofibers*
Neointima / prevention & control
Rats
Sutures
Tacrolimus* / therapeutic use

Substances

Tacrolimus

Grants and funding

R01 HL141612/HL/NHLBI NIH HHS/United States