Controlling the balance of endothelial cells (ECs) and smooth muscle cells (SMCs) in blood vessels is critically important to minimize the risk associated with vascular implants. Extracellular matrix (ECM) plays a key role in controlling the cellular balance, suggesting a promising source of cell-selective peptides. To obtain EC- or SMC-selective peptides, we start by highlighting sequence differences found among ECM molecules as enriched targets for cell-selective peptides. We explored the EC- or SMC-selective performance of tripeptides that are specifically enriched only in collagen type IV, but not in types I, II, III, and V. Collagen type IV was chosen since it is the major ECM in the basement membrane of blood vessels, which separates ECs and SMCs. Among 114 collagen type IV-derived tripeptides pre-screened from in silico analysis, 22 peptides (19%) were found to promote cell-selective adhesion, as determined by peptide array. One of the best performing EC-selective peptides (Cys-Ala-Gly (CAG)) was mixed into an electrospun fine-fiber, a vascular graft material, for practical application. Compared to unmodified fiber, the CAG containing fiber surface was found to enhance adhesion of ECs (+190%) while limiting SMCs (-20%). These results are not only consistent with the hypothesis of ECM as a source of cell selective peptides, but also suggest a new genre of EC- or SMC-selective peptides for tissue engineering applications. Collectively, these findings favorably support the screening approach used to discover new peptides for these purposes.

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The concept of tissue engineered small-caliber vascular grafts (TE-SCVGs) is theoretically ideal. In this study, we evaluated the long-term (more than 1 year) course of TE-SCVGs using a rat carotid arterial replacement model. We fabricated a TE-SCVG scaffold (0.7 mm in diameter) with electrospun nano-scale fibers. Poly-ε-caprolactone was used as a biodegradable polymer. These artificial vessels were then used in carotid arterial replacement performed on Sprague-Dawley rats. The implanted grafts were removed at an early phase (1, 2, 6 weeks), middle phase (12, 24 weeks), and late phase (48, 72 weeks) after implantation. Twenty-nine patent grafts from among the 40 implanted grafts (patency 72.5 %) could be evaluated. No aneurysm formation was observed during the follow-up period. Endothelial cells positive for immunostaining with von Willebrand factor were found to be already attached to the inner surface of the TE-SCVGs in the early phase. The percentage of smooth muscle cell specific marker (α-smooth muscle actin and calponin with fluorescent immunostaining) positive cells, which seemed to be mesenchymal cells in the graft wall, increased with time, while, in contrast, the scaffold material decreased. Even after 72 weeks, however, although the scaffold material had degraded, it had not disappeared completely. These results show that the novel TE-SCVGs we developed were still functioning in the rat carotid arterial circulation after more than 1 year. However, further investigations will be required with regard to regeneration of the SMC layer and the complete degradation of graft materials.

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Paravalvular leakage (PVL) remains an unavoidable late complication after valve surgery. We indicate surgery only cases with progressive congestive heart failure and/or hemolytic anemia. We review our clinical experiences of PVL surgery. Between 1992 and 2009 we experienced 8 cases of aortic PVL-6 subjects after primary aortic valve replacement (AVR) and 2 subjects after re-AVR-and 10 subjects with mitral PVL-5 cases after primary mitral valve replacement (MVR) and 5 cases after re-MVR. Mitral PVL began in the later phases after surgery and had more severe symptoms, because of heart failure and/or hemolytic anemia, than aortic PVL. Aortic PVL occurred more frequently because of laxation of sutured threads without frequent sites. Conversely, mitral PVL was mainly caused by cutting annulus tissue around the anterior commisurae after primary MVR, and by a valve-on-valve structure on the middle scallop of the posterior leaflet or circumferentially after re-MVR. All operations were performed safely and all patients were discharged uneventfully. No cases experienced recurrence of PVL in the follow-up period. The symptoms of PVL became exacerbated, and our surgical indications based on these symptoms were validated. Valve-on-valve replacement, which was a major cause of PVL after re-MVR, should be avoided in a re-MVR procedure. Cautious follow-up is necessary, even in the late phase after surgery, especially for patients who have undergone MVR.