title: Development of novel drug-eluting biodegradable nano-fiber for prevention of postoperative pulmonary venous obstruction.
abstract: 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.
authors.affiliation: Department of Cardiac Surgery, Nagoya University, Graduate School of Medicine, Nagoya, Aichi, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Mutsuga
authors.forename: Yuji
authors.initials: Y
authors.lastname: Narita
authors.forename: Aika
authors.initials: A
authors.lastname: Yamawaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Satake
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kaneko
authors.forename: Akihiko
authors.initials: A
authors.lastname: Usui
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ueda
mesh_terms: D020341:Absorbable Implants; D000714:Anastomosis, Surgical; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008422:Materials Testing; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D049329:Nanostructures; D011098:Polyglactin 910; D011474:Prosthesis Design; D011668:Pulmonary Veno-Occlusive Disease / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000008:administration & dosage*; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D014682:Vena Cava, Inferior / Q000187:drug effects* / Q000473:pathology / Q000601:surgery
chemical_list: D002317:Cardiovascular Agents; D011098:Polyglactin 910; D016559:Tacrolimus