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透析治疗中同种异体移植物的生物替代物:羊模型中自体生物人工血液透析分流器的评估。

A biological alternative to alloplastic grafts in dialysis therapy: evaluation of an autologised bioartificial haemodialysis shunt vessel in a sheep model.

机构信息

Center of Competence for Cardiovascular Implants-Medimplant, Department of Cardiac Surgery, Hannover Medical School, Hannover, Germany.

出版信息

Eur J Vasc Endovasc Surg. 2010 Dec;40(6):810-6. doi: 10.1016/j.ejvs.2010.04.023. Epub 2010 Jun 8.

DOI:10.1016/j.ejvs.2010.04.023
PMID:20965129
Abstract

OBJECTIVES

To evaluate bioartificial haemodialysis access grafts in a sheep model with respect to patency and morphology.

MATERIAL AND METHODS

Bovine internal thoracic arteries (n=28) were decellularised. Fourteen grafts (DC grafts) were directly implanted as cervical AV shunts, the remaining were re-seeded with endothelial cells (ECs) derived from blood samples of the later ovine recipient (EC grafts) first. Following simulated punctures and duplex ultrasound scans to determine patency, grafts were explanted for immunohistochemical characterisation after 3 and 6 months, respectively. DC grafts underwent biomechanical testing for compliance (C), suture retention strength (SRT), and burst pressure (BP) before (n=6) and after (n=6) implantation.

RESULTS

Following 3 and 6 months, the majority of EC (n=6/6; n=6/7) and DC grafts (n=5/6; n=5/7) were patent and not relevantly stenosed (peak systolic velocity: EC grafts=76 cm s(-1)±4; DC grafts=77 cm s(-1)±5). Simulated haemodialysis punctures revealed significantly shorter bleeding times in all bioartificial grafts than in native jugular veins (P>0.001). Comparing native carotid arteries with DC grafts prior to and post-implantation, the latter differed significantly with respect to C (P>0.001; P=0.005), whereas only pre-implant DC grafts differed regarding BP (P=0.002); no differences were observed for SRT. Histology revealed complete endothelial surface coverage of EC, but not DC grafts. Furthermore, DC grafts exhibited areas of pronounced tissue calcification.

CONCLUSION

The preclinical development of a bioartificial haemodialysis access graft with promising mechanical and morphological properties in a sheep model is feasible.

摘要

目的

通过羊模型评估生物人工血液透析血管通路移植物的通畅性和形态。

材料和方法

牛胸内动脉(n=28)被去细胞化。14 个移植物(DC 移植物)被直接植入作为颈内静脉-颈外静脉动静脉分流术,其余的首先用来自后期绵羊受体的血液样本中分离出来的内皮细胞(EC 移植物)再种植。在模拟穿刺和双功能超声扫描确定通畅性后,分别在 3 个月和 6 个月时取出移植物进行免疫组织化学特征分析。在植入前(n=6)和植入后(n=6),对 DC 移植物进行顺应性(C)、缝线保持强度(SRT)和破裂压力(BP)的生物力学测试。

结果

在 3 个月和 6 个月后,大多数 EC(n=6/6;n=6/7)和 DC 移植物(n=5/6;n=5/7)是通畅的,没有明显狭窄(峰值收缩速度:EC 移植物=76 cm s(-1)±4;DC 移植物=77 cm s(-1)±5)。模拟血液透析穿刺显示,所有生物人工移植物的出血时间明显短于天然颈静脉(P>0.001)。与植入前后的天然颈动脉相比,后者在 C 方面有显著差异(P>0.001;P=0.005),而仅在植入前的 DC 移植物在 BP 方面有显著差异(P=0.002);SRT 没有差异。组织学显示 EC 完全覆盖内皮表面,但 DC 移植物没有。此外,DC 移植物显示出明显的组织钙化区域。

结论

在羊模型中,具有有前途的机械和形态学特性的生物人工血液透析血管通路移植物的临床前开发是可行的。

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