title: Investigation of the long-term patency of a transmural heparinized polycaprolactone and poly(D,L-lactic/glycolic acid) scaffold.
abstract: BACKGROUND
  The transmural biodegradable polycaprolactone/poly(D,L-lactic/glycolic acid) (PCL/PLGA) scaffold is a promising modality for diffuse coronary atherosclerosis cases that are not suitable for bypass grafting. The purpose of this study was to evaluate the long-term performance of the PCL/PLGA scaffold in vivo in the setting of polymer and heparin degradation.
  
  
  METHODS
  After mechanical drilling through the ventricular wall was performed in the whole ventricular wall, two scaffolds were implanted into the ventricular wall. Animals were grouped into the single drilling group (SD group), the blank scaffold group (BS group), and the heparinized scaffold group (HS group) and were allowed to survived for 6 mo. Next, the patency and integrity of the scaffolds were evaluated by echocardiography and 3D-DOCTOR software. Endothelium coverage of the lumen was evaluated by scanning electron microscopy. Neovessels and collagen fiber within the scaffolds were identified by histologic staining. Metabolite production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in the plasma was measured by an enzyme-linked immunosorbent assay. The expression levels of PGI2 synthase and cyclooxygenase 2 (COX-2) involved in PGI2 production and COX-1 involved in TXA2 production were measured by Western blot analysis.
  
  
  RESULTS
  The heparinized scaffolds were patent for up to 6 mo and the lumen was covered with confluent endothelial cells. Histologic staining revealed collagen fiber remodeling and reconstruction of the neovascular network immediately surrounding the lumen. The expression of PGI2 synthase and COX-2 in the HS group was significantly higher compared with the SD and BS groups (P < 0.01). The expression of COX-1 was similar in the three groups (P > 0.05). Consistent with synthetase expression, a PGI2 metabolite (6-keto-PGF1a) also showed a significant increase in the HS group relative to the SD and BS groups (P = 0.021 and P = 0.015, respectively). Concomitantly, as a PGI2 antagonist, the TXA2 metabolite (TXB2) did not exhibit a significant difference among the three groups (P = 0.17).
  
  
  CONCLUSIONS
  Despite polymer and heparin degradation, the scaffold could continuously maintain the structural integrity and lumen patency for up to 6 mo by reinforcement of host collagen fiber and the balance of PGI2/TXA2.
authors.affiliation: Department of Cardiovascular Surgery, Zhengzhou University People's Hospital, Zhengzhou, China; Department of Cardiovascular Surgery, Henan Provincial People' Hospital, Zhengzhou, Henan Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Cardiovascular Surgery, Zhengzhou University People's Hospital, Zhengzhou, China; Department of Cardiovascular Surgery, Henan Provincial People' Hospital, Zhengzhou, Henan Province, China. Electronic address: luli04301608@126.com.
authors.forename: Zhaoyun
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Cardiovascular Surgery, Zhengzhou University People's Hospital, Zhengzhou, China; Department of Cardiovascular Surgery, Henan Provincial People' Hospital, Zhengzhou, Henan Province, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Cardiovascular Surgery, Zhengzhou University People's Hospital, Zhengzhou, China; Department of Cardiovascular Surgery, Henan Provincial People' Hospital, Zhengzhou, Henan Province, China.
authors.forename: Ziniu
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Molecular Design Laboratory, Institute of Biomedical Engineering, Peking Union Medical College, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lü
authors.affiliation: Department of Cardiovascular Surgery, TEDA International Cardiovascular Hospital, Tianjin, China.
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Liu
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001672:Biocompatible Materials / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004452:Echocardiography; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D011464:Epoprostenol / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D019344:Lactic Acid / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D011091:Polyesters / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013552:Swine; D013556:Swine, Miniature; D013928:Thromboxane A2 / Q000378:metabolism; D054457:Tissue Scaffolds; D014654:Vascular Patency
chemical_list: D000925:Anticoagulants; D001672:Biocompatible Materials; D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013928:Thromboxane A2; D006493:Heparin; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Coronary artery disease; Endothelial cells; Heparin; Patency; Prostacyclin; Scaffold