Aortic valve neocuspidization with in-body tissue-engineered autologous membranes: preliminary results in a long-term goat model

Aortic valve neocuspidization with in-body tissue-engineered autologous membranes: preliminary results in a long-term goat model
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DOI:
10.1093/icvts/ivab015
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发表时间:
2021-02-05
影响因子:
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通讯作者:
Miyamoto, Shinji
Miyamoto, Shinji
中科院分区:
医学4区
文献类型:
--
作者:
Kawashima, Takayuki;Umeno, Tadashi;Miyamoto, Shinji

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目的:主动脉瓣新尖化已显示出令人满意的临床结局;然而,自体心包的耐久性是年轻患者的一个问题。本研究应用自体胶原膜(Biosheet(R)),在体内组织结构,主动脉瓣新生,并研究其长期的结果在山羊模型。方法:模具埋在6只山羊皮下。2个月后,在模具中形成生物片。我们使用一部分厚度为0.20-0.35 mm的薄片进行主动脉瓣新生,通过光学相干断层扫描进行测量。在6个月(n= 3)和12个月(n= 3)时对动物进行超声心动图和组织学评价。作为对照,戊二醛处理的自体心包被用于在12 months.RESULTS:所有动物都存活了预定的时间在4山羊,类似的评价。6个月时,Biosheets维持了瓣膜功能并表现出再生反应:与瓣环融合、细胞浸润到瓣叶以及心室侧出现弹性纤维。12个月后,再生结构几乎没有变化,没有退化,1/9瓣叶中的钙化可忽略不计。然而,所有病例均发生1处瓣叶撕裂,导致中度至重度主动脉瓣返流。在心包组中,四分之三的动物经历了中度至重度主动脉瓣返流与高钙化率(9/12小叶)。结论:Biosheets可能具有再生潜力和抗钙化特性,与自体心包。然而,为了获得可靠的结果,还需要进一步改进,严格控制和优化其厚度、密度和均匀性。
OBJECTIVES: Aortic valve neocuspidization has shown satisfactory clinical outcomes; however, autologous pericardium durability is a concern for young patients. This study applied an autologous collagenous membrane (Biosheet (R)), produced by in-body tissue architecture, to aortic valve neocuspidization and investigated its long-term outcome in a goat model.METHODS: Moulds were embedded subcutaneously in 6 goats. After 2 months, Biosheets formed in the moulds. We performed aortic valve neocuspidization using a portion of the sheets with a thickness of 0.20-0.35 mm, measured by optical coherence tomography. Animals were subjected to echocardiography and histological evaluation at 6 months (n= 3) and 12 months (n= 3). As a control, the glutaraldehyde-treated autologous pericardium was used in 4 goats that were similarly evaluated at 12 months.RESULTS: All animals survived the scheduled period. At 6 months, Biosheets maintained valve function and showed a regeneration response: fusion to the annulus, cell infiltration to the leaflets and appearance of elastic fibres at the ventricular side. After 12 months, the regenerative structure had changed little without regression, and there was negligible calcification in the 1/9 leaflets. However, all cases had one leaflet tear, resulting in moderate-to-severe aortic regurgitation. In the pericardium group, three-fourths of the animals experienced moderate-to-severe aortic regurgitation with a high rate of calcification (9/12 leaflets).CONCLUSIONS: Biosheets may have regeneration potential and anti-calcification properties in contrast to autologous pericardium. However, in order to obtain reliable outcome, further improvements are required to strictly control and optimize its thickness, density and homogeneity.