A new strategy for prevention of anastomotic stricture using tacrolimus-eluting biodegradable nanofiber

Mutsuga, Masato; Narita, Yuji; Yamawaki, Aika; Satake, Makoto; Kaneko, Hiroaki; Suematsu, Yoshihiro; Usui, Akihiko; Ueda, Yuichi

doi:10.1016/j.jtcvs.2008.11.017

« Previous Next »The Journal of Thoracic and Cardiovascular Surgery
Volume 137, Issue 3 , Pages 703-709, March 2009

A new strategy for prevention of anastomotic stricture using tacrolimus-eluting biodegradable nanofiber

Masato Mutsuga, MD
- Nagoya University, Graduate School of Medicine, Department of Cardiothoracic Surgery, Nagoya, Aichi, Japan
Yuji Narita, MD, PhD
- Nagoya University, Graduate School of Medicine, Department of Cardiothoracic Surgery, Nagoya, Aichi, Japan
- Department of Clinical Cell Therapy and Tissue Engineering, Nagoya University School of Medicine, Nagoya, Aichi, Japan
- Address for reprints: Yuji Narita, MD, PhD, Department of Clinical Cell Therapy and Tissue Engineering, Nagoya University School of Medicine, 65 Tsurumaicho, Syowa-ku, Nagoya, Aichi 466-8550, Japan.
Aika Yamawaki, BMedEng
- Department of Clinical Cell Therapy and Tissue Engineering, Nagoya University School of Medicine, Nagoya, Aichi, Japan
Makoto Satake, PhD
- Department of Tissue Engineering Development, Teijin Technology Innovation Center, Teijin Limited, Hino, Tokyo, Japan
Hiroaki Kaneko, PhD
- Department of Tissue Engineering Development, Teijin Technology Innovation Center, Teijin Limited, Hino, Tokyo, Japan
Yoshihiro Suematsu, MD, PhD
- Department of Cardiac Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
Akihiko Usui, MD, PhD
- Nagoya University, Graduate School of Medicine, Department of Cardiothoracic Surgery, Nagoya, Aichi, Japan
Yuichi Ueda, MD, PhD
- Nagoya University, Graduate School of Medicine, Department of Cardiothoracic Surgery, Nagoya, Aichi, Japan

Received 19 June 2008; received in revised form 2 October 2008; accepted 15 November 2008.

Objective

We developed a novel sustained drug-eluting device using tacrolimus-eluting biodegradable nanofiber to prevent anastomotic stricture and evaluated the effects in a rat abdominal aortic anastomosis model.

Methods

In vitro and in vivo tacrolimus release tests for tacrolimus-eluting biodegradable nanofiber were performed to confirm its sustained release. To verify the prevention of anastomotic stricture, tacrolimus-eluting biodegradable nanofiber was placed around the end-to-end anastomosis of abdominal aorta in rats. Five rats were allocated to the following 5 groups: (1) control without tacrolimus-eluting biodegradable nanofiber, (2) 5 mg of nanofiber only (0 wt% of tacrolimus), (3) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.04 wt% of tacrolimus, (4) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 0.1 wt% of tacrolimus, and (5) 5 mg of tacrolimus-eluting biodegradable nanofiber containing 1.0 wt% of tacrolimus. Morphometric and histologic analyses including immunohistochemistry were performed in each of the groups 2 weeks after the operation.

Results

The tacrolimus-eluting biodegradable nanofiber gradually released tacrolimus for at least 1 month in vitro and in vivo. The ratio of intimal area was significantly reduced in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group compared with the other groups (0.26, 0.24, 0.25, 0.21, and 0.08 in control, 0 wt%, 0.04 wt%, 0.1 wt%, and 1.0 wt%, respectively, P < .05). The cells, which constitute intimal hyperplasia, were positive for smooth muscle actin and SMemb, and factor VIII revealed that endothelial cells covered the surface of the aortic lumen even in the 1.0 wt% tacrolimus-eluting biodegradable nanofiber group in immunohistochemistry.

Conclusion

Tacrolimus-eluting biodegradable nanofiber reduced neointimal hyperplasia and preserved endothelialization. This device may be useful in the prevention of anastomotic stricture.

CTSNet classification: 18, 23, 33

Abbreviations and Acronyms: H&E, hematoxylin-eosin, TEBN, tacrolimus-eluting biodegradable nanofiber, VSMC, vascular smooth muscle cell