title: A new tissue-engineered biodegradable surgical patch for high-pressure systems †.
abstract: OBJECTIVE
  Ideal alternatives for replacing native arteries, which have biocompatibility such as growth potential, anti-thrombogenesis and durability, have yet to be discovered. We previously demonstrated the utility of tissue-engineered vascular autografts; however, the use of these autografts is limited to low-pressure conditions. The aim of this study was to create the tissue-engineered arterial patch (TEAP) that could be used in high-pressure systems, and to evaluate the maturation in this regenerative tissue.
  
  
  METHODS
  We developed a new biodegradable polymer scaffold, which is composed of a co-polymer of epsilon-caprolactone and lactide acid [P(CL/LA)] and a poly-L-lactide acid (PLLA). To obtain mechanical strength, we modified PLLA that is degraded by hydrolysis for 1-2 years in contrast to polyglycolic acid in our low-pressure study previously. We implanted an oval-shaped patch (30 × 15 mm) of this polymer without cell seeding into the descending aorta of 12 dogs, and followed the animals for 1, 3 and 6 months (n = 4 in each group). The cell proliferation in the patch was evaluated with histological and immunohistochemical methods. Additionally, the expression of vascular endothelial growth factor (VEGF) and smooth muscle myosin heavy chain (smMHC) mRNA in the patches was determined with reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  Macroscopically, there was no incidence of rupture or aneurysmal formation on the patch. The luminal surface of the TEAP was covered with a single layer of endothelial cells stained with vWF immunohistochemically at 1 month after implantation. αSMA-positive cells that indicated smooth muscle cells and collagen fibres were observed in the patch and they increased over time. The VEGF mRNA expression in the patch at 1 month was significantly higher than that of native arterial tissue (1 month; 0.124 ± 0.017 ng/µl, native; 0.009 ± 0.003 ng/µl, P < 0.05). The smMHC mRNA expression gradually increased, and reached ∼ 60% of that of the native artery at 6 months (6 months: 0.351 ± 0.028 ng/µl, native: 0.540 ± 0.027 ng/µl).
  
  
  CONCLUSIONS
  We demonstrated the maturation of endothelial and smooth muscle cells in TEAP, suggesting that this biodegradable polymer scaffold could be used as an alternative vascular material even in high-pressure systems.
authors.affiliation: Department of Cardiovascular Surgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ichihara
authors.affiliation: Department of Surgery, Ohio State University, The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA toshiharu.shinoka@nationwidechildrens.org.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Shinoka
authors.affiliation: Department of Cardiovascular Surgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Goki
authors.initials: G
authors.lastname: Matsumura
authors.affiliation: Department of Indoor Environmental Medicine, Nara Medical University, Kashihara-shi, Nara, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ikada
authors.affiliation: Department of Cardiovascular Surgery, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000502:physiology / Q000601:surgery*; D062186:Arterial Pressure; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D004285:Dogs; D042783:Endothelial Cells / Q000378:metabolism; D024022:Fibrillar Collagens / Q000378:metabolism; D006868:Hydrolysis; D019344:Lactic Acid / Q000737:chemistry; D008422:Materials Testing; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011474:Prosthesis Design; D011475:Prosthesis Failure; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow; D013314:Stress, Mechanical; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D066253:Vascular Remodeling
chemical_list: D024022:Fibrillar Collagens; D011091:Polyesters; D011108:Polymers; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D019344:Lactic Acid; C033616:poly(lactide); C062968:lactide-caprolactone copolymer; D018995:Myosin Heavy Chains
keywords: Biodegradable scaffold; High-pressure systems; Tissue engineering; Vascular autograft