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组织工程三尖瓣的中期功能及重塑潜力:组织学与生物力学

Mid-term function and remodeling potential of tissue engineered tricuspid valve: Histology and biomechanics.

作者信息

Ropcke Diana M, Rasmussen Jonas, Ilkjær Christine, Skov Søren N, Tjørnild Marcell J, Baandrup Ulrik T, Christian Danielsen Carl, Hjortdal Vibeke E, Nielsen Sten L

机构信息

Dept. of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; Dept. of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.

Dept. of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark; Dept. of Clinical Medicine, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark.

出版信息

J Biomech. 2018 Apr 11;71:52-58. doi: 10.1016/j.jbiomech.2018.01.019. Epub 2018 Feb 2.

DOI:10.1016/j.jbiomech.2018.01.019
PMID:29428174
Abstract

OBJECTIVE

Tricuspid valve reconstruction using a small intestinal submucosal porcine extracellular matrix (ECM) tube graft is hypothesized to be durable for six months and show signs of recellularization and growth potential. The purpose was to histologically and biomechanically test ECM valves before and after six months of implantation in pigs for comparison with native valves.

METHODS

Ten 60 kg pigs were included, which survived tricuspid valve tube graft insertion. Anterior and septal tricuspid leaflets were explanted from all animals surviving more than one month and examined histologically (n = 9). Endothelialization, collagen content, mineralization, neovascularization, burst strength and tensile strength were determined for native valves (n = 5), ECM before implantation (n = 5), and ECM after six months (n = 5).

RESULTS

Collagen density was significantly larger in ECM at implantation (baseline) compared to native leaflet tissue (0.3 ± 0.02 mg/mm vs. 0.1 ± 0.03 mg/mm, p < .0001), but collagen density decreased and reached native leaflet collagen content, six months after ECM implantation (native vs. ECM valve at six months: 0.1 ± 0.03 mg/mm vs. 0.2 ± 0.05 mg/mm, p = .8). Histologically, ECM valves showed endothelialization, host cell infiltration and structural collagen organization together with elastin generation after six months, indicating tissue remodeling and -engineering together with gradual development of a close-to-native leaflet structure without foreign body response.

CONCLUSIONS

ECM tricuspid tube grafts were stronger than native leaflet tissue. Histologically, the acellular ECM tube grafts showed evidence of constructive tissue remodeling with endothelialization and connective tissue organization. These findings support the concept of tissue engineering and recellularization, which are prerequisites for growth.

摘要

目的

假设使用小肠黏膜下层猪细胞外基质(ECM)管型移植物进行三尖瓣重建可维持六个月的耐久性,并显示出再细胞化和生长潜力的迹象。目的是在猪体内植入ECM瓣膜六个月前后进行组织学和生物力学测试,以便与天然瓣膜进行比较。

方法

纳入10头60千克的猪,这些猪在三尖瓣管型移植物植入后存活。从所有存活超过一个月的动物中取出前叶和隔叶三尖瓣小叶,并进行组织学检查(n = 9)。测定天然瓣膜(n = 5)、植入前的ECM(n = 5)和六个月后的ECM(n = 5)的内皮化、胶原蛋白含量、矿化、新生血管形成、破裂强度和拉伸强度。

结果

与天然小叶组织相比,植入时(基线)ECM中的胶原蛋白密度显著更高(0.3±0.02毫克/毫米对0.1±0.03毫克/毫米,p <.0001),但在ECM植入六个月后,胶原蛋白密度降低并达到天然小叶胶原蛋白含量(六个月时天然瓣膜与ECM瓣膜:0.1±0.03毫克/毫米对0.2±0.05毫克/毫米,p =.8)。组织学上,ECM瓣膜在六个月后显示出内皮化、宿主细胞浸润和结构性胶原蛋白组织以及弹性蛋白生成,表明组织重塑和工程化以及逐渐发展出接近天然小叶结构且无异物反应。

结论

ECM三尖瓣管型移植物比天然小叶组织更强。组织学上,无细胞ECM管型移植物显示出具有内皮化和结缔组织组织的建设性组织重塑证据。这些发现支持组织工程和再细胞化的概念,这是生长的先决条件。

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