Long-Term Results of Cell-Free Biodegradable Scaffolds for In Situ Tissue-Engineering Vasculature: In a Canine Inferior Vena Cava Model

We have developed a new biodegradable scaffold that does not require any cell seeding to create an in-situ tissue-engineering vasculature (iTEV). Animal experiments were conducted to test its characteristics and long-term efficacy. An 8-mm tubular biodegradable scaffold, consisting of polyglycolide knitted fibers and an L-lactide and ε-caprolactone copolymer sponge with outer glycolide and ε-caprolactone copolymer monofilament reinforcement, was implanted into the inferior vena cava (IVC) of 13 canines. All the animals remained alive without any major complications until euthanasia. The utility of the iTEV was evaluated from 1 to 24 months postoperatively. The elastic modulus of the iTEV determined by an intravascular ultrasound imaging system was about 90% of the native IVC after 1 month. Angiography of the iTEV after 2 years showed a well-formed vasculature without marked stenosis or thrombosis with a mean pressure gradient of 0.51±0.19 mmHg. The length of the iTEV at 2 years had increased by 0.48±0.15 cm compared with the length of the original scaffold (2–3 cm). Histological examinations revealed a well-formed vessel-like vasculature without calcification. Biochemical analyses showed no significant differences in the hydroxyproline, elastin, and calcium contents compared with the native IVC. We concluded that the findings shown above provide direct evidence that the new scaffold can be useful for cell-free tissue-engineering of vasculature. The long-term results revealed that the iTEV was of good quality and had adapted its shape to the needs of the living body. Therefore, this scaffold would be applicable for pediatric cardiovascular surgery involving biocompatible materials

Utility and safety of nafamostat mesilate for anticoagulation in dogs

Abstract Background Surgical interventions are recommended for cases of advanced mitral regurgitation, however, limited facilities are available. The most prominent complication in such procedures is heparin‐derived bleeding. An alternative anticoagulant to heparin, nafamostat mesilate (NM), can reduce the occurrence of complications associated with heparin such as bleeding or shock. Objectives This study aimed to evaluate the utility and safety of using NM during anaesthesia in canines. Methods Six healthy adult Beagle dogs were anaesthetised, and NM was administered intravenously as a 10 mg/kg bolus dose over 5 min, followed by a continuous infusion of 10 mg/kg/h over 20 min. Blood tests and blood pressure measurements were performed at 0, 5, 25 and 55 min after NM administration. Results Activated thromboplastin times at 0, 25 and 55 min were 13.0 ± 0.7 s, 106.7 ± 13.3 s and 28.2 ± 2.9 s, respectively, with a significant difference between 0 and 25 min (p < 0.01) only. No significant differences were observed in prothrombin time, antithrombin, fibrinogen and fibrin degradation product concentrations between timepoints. Activated clotting times (ACTs) at 0, 5, 25 and 55 min were 119.5 ± 9.6 s, 826.7 ± 78.6 s, 924.8 ± 42.4 s and 165.2 ± 13.5 s, respectively. Significant differences were observed between 0 and 5 min (p < 0.05) and between 0 and 25 min (p < 0.05). Blood pressure changes occurred in four dogs (66.7%). No other serious adverse effects were observed. Conclusions ACT results indicated that NM use in anaesthetised healthy dogs was sufficient to obtain procedural anticoagulation with minimal adverse effects. However, these preliminary data require validation in further studies on cardiopulmonary bypass surgery

Biomechanical analyses of IVC and <i>i</i>TEV at 2 years.

<p>A, representative P–S loop data for control scaffold and <i>i</i>TEV and native IVC at 2 yr; P–S loops from time-dependent strain and pressure measurements , used to calculate sample elastic moduli. B, elastic moduli ratios of <i>i</i>TEV to native IVC at 0 (control), 1, 2.5, 6, 12, and 24 months (n = 7); significant differences between control and samples (<i>p</i><0.0001 by ANOVA); ***, <i>p</i><0.001, control vs. 1 month and **, <i>p</i><0.01, control vs. 2.5–24 months by Dunnett's <i>post hoc</i> test. C, <i>i</i>TEV RS at 1, 2.5, 6, 12, and 24 months (n = 7); RS maintained by scaffold while tissue in infancy; data show <i>i</i>TEV elasticity not affected by time after implantation; Note, P(GA/CL) monofilament and P(LA/CL) sponge scaffold lose strength within ∼2.5 and 6 months, respectively (<i>p</i> = 0.443 by ANOVA); NS, not significant.</p

Biochemical analyses of the <i>i</i>TEV and IVC at 2 years.

<p>A–C, elastin, hydroxyproline, and calcium contents in IVC and <i>i</i>TEV at 2 years; data, means ±SEM (<i>n</i> = 7 each); no significant differences (elastin, <i>p</i> = 0.615 and hydroxyproline, <i>p</i> = 0.750 by Student's <i>t</i>-test; calcium, <i>p</i> = 0.165 by the Mann–Whitney U test); NS, not significant.</p

Overview of the new biodegradable scaffold and its degradation.

<p>A, biodegradable scaffold 8 mm in diameter; bar, 1 cm. B, tensile strength changes in biodegradable scaffolds <i>in vitro</i>; scaffold strength diminished remarkably over 4 weeks. C, Mw changes in scaffold immersed in 37°C PBS; gradual hydrolysis decreased Mw.</p