Development of novel drug-eluting biodegradable nano-fiber for prevention of postoperative pulmonary venous obstruction

• Published in: Interactive cardiovascular and thoracic surgery Vol. 8; no. 4; pp. 402 - 407
• Main Authors: Mutsuga, Masato, Narita, Yuji, Yamawaki, Aika, Satake, Makoto, Kaneko, Hiroaki, Usui, Akihiko, Ueda, Yuichi
• Format: Journal Article
• Language: English
• Published: England Eur Assoc Cardio Surg 01.04.2009; European Association for Cardio-Thoracic Surgery
• Subjects: Absorbable Implants; Anastomosis, Surgical; Animals; Cardiovascular Agents - administration & dosage; Cell Proliferation - drug effects; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Eluting Stents; Humans; Hyperplasia; Male; Materials Testing; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - pathology; Nanostructures; Polyglactin 910; Prosthesis Design; Pulmonary Veno-Occlusive Disease - etiology; Pulmonary Veno-Occlusive Disease - pathology; Pulmonary Veno-Occlusive Disease - prevention & control; Rats; Rats, Wistar; Tacrolimus - administration & dosage; Time Factors; Tunica Intima - drug effects; Tunica Intima - pathology; Vena Cava, Inferior - drug effects; Vena Cava, Inferior - pathology; Vena Cava, Inferior - surgery; Pulmonary venous obstruction; Tacrolimus; Intimal hyperplasia; Total anomalous pulmonary venous connection; Nano-fiber
• ISSN: 1569-9293; 1569-9285
• DOI: 10.1510/icvts.2008.192831

a Department of Cardiac Surgery, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan b Department of Clinical Cell Therapy and Tissue Engineering, Nagoya University School of Medicine, 65 Tsurumaicho Showa-ku, Nagoya, Aichi, 466-8550, Japan c Department of Tissue Engineering Development, Technology Innovation Center, Teijin Limited, Hino, Tokyo, Japan *Corresponding author. Tel.: +81-52-744-2424; fax: +81-52-744-1978. E-mail address : ynarita{at}med.nagoya-u.ac.jp (Y. Narita). Pulmonary venous obstruction (PVO) after correction of total anomalous pulmonary venous connection (TAPVC) frequently occurs due to intimal-hyperplasia and the required re-operation. We have developed a novel sustained-release drug delivery system, using Tacrolimus-eluting biodegradable nano-fiber (TEBN). It consists of nano-scale fiber composed of biodegradable polymer and Tacrolimus. This study evaluated the effects of TEBN for prevention of venous anastomotic stricture in a rat model to apply to PVO operation. Tacrolimus was incorporated into poly ( L -lactide-co-glycolide). The venous stricture model was made by rat inferior vena cava anastomosis. The IVC anastomosis was covered with TEBN with 1.0 wt% Tacrolimus ( n =12) or without TEBN as a control ( n =12), and evaluated histologically at 1, 2, and 4 weeks after operation. The ratio of intimal area was significantly reduced in the TEBN group compared with the control group (ratio; 1 week: 0.43±0.26 vs. 0.07±0.04, P =0.04, 2 weeks: 0.39±0.19 vs. 0.05±0.02, P =0.01, 4 weeks: 0.31±0.15 vs. 0.09±0.04, P =0.03, control vs. TEBN, respectively). Histological findings showed endothelialization along the inner surface of the vein even in TEBN. The TEBN reduced intimal hyperplasia and preserved endothelialization even in a venous stricture. These results suggested that this strategy might be useful for prevention of recurrent PVO after TAPVC correction. Key Words: Pulmonary venous obstruction; Total anomalous pulmonary venous connection; Tacrolimus; Nano-fiber; Intimal hyperplasia