Application of a degradable thin film to modulate perfusion to post-autotransplantation airways in rats

JTCVS open Pub Date : 2025-04-01 DOI:10.1016/j.xjon.2025.01.008

Aravind Krishnan MD , Mahdi Forouharshad PhD , Elbert Heng MD , Alyssa Garrison MS , Daniel Alnasir BSE , Shubham Patil BS , Arman Farazdaghi BS , Moeed Fawad MS , Stefan Elde MD , Brandon A. Guenthart MD , Laura M. Ensign PhD , Y Joseph Woo MD , Kunal S. Parikh PhD , John W. MacArthur MD

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Abstract

Objective

Recipients of lung transplants experience the lowest long-term survival among all solid-organ transplant recipients. Airway complications contribute significantly to morbidity and mortality post-lung transplant and may be driven by airway devascularization inherent to procurement and implantation of the lungs. We studied application of biodegradable, nanofiber-based thin films to devascularized autotransplanted airways to mitigate airway ischemia.

Methods

We used a rat tracheal autotransplantation model that replicates airway ischemia. Rats were divided into an operated control group (n = 18) and a treatment group (n = 12) receiving an electrospun film composed of randomly aligned polydioxanone (PDO) nanofibers applied to the circumferential surface of the transplanted trachea. Airway perfusion was assessed via laser speckle contrast analysis at 0, 3, and 10 days. Differences in perfusion units were calculated between the nontransplanted and transplanted segments of the trachea. Multimodal analysis of angiogenesis in tracheal autografts included immunoassay profiling for proangiogenic cytokines, histologic injury grading, and speckle angiography.

Results

Qualitative and quantitative perfusion differences were demonstrated at days 0, 3, and 10. Nanofiber-based, PDO thin films significantly improved perfusion in the transplanted segment of trachea (P < .05). Histologic injury scoring was significantly worse in the operated controls compared with the treatment group (P < .01). Immunoassays demonstrated increased expression of vascular cell adhesion molecule 1 in the treatment group (P < .05).

Conclusions

Application of a nanofiber-based, PDO thin film induced a local tissue response that improved perfusion and histologic injury scoring of the transplanted airway in an autotransplant model of airway devascularization. Immune multiplexing suggests local inflammatory responses may drive angiogenesis.

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可降解薄膜在大鼠自体移植后气道灌注调节中的应用

目的在所有实体器官移植受者中，肺移植受者的长期生存率最低。气道并发症对肺移植后的发病率和死亡率有重要影响，可能是由肺部获取和植入所固有的气道断流造成的。我们研究了生物可降解的纳米纤维薄膜在断流的自体移植气道中的应用，以减轻气道缺血。方法采用复制气道缺血的大鼠气管自体移植模型。大鼠分为手术对照组（n = 18）和治疗组（n = 12），采用随机排列的聚二氧环酮纳米纤维组成的静电纺丝膜涂于移植气管周表面。在第0、3、10天通过激光散斑对比分析评估气道灌注。计算未移植气管段与移植气管段灌注单位的差异。气管自体移植物血管生成的多模式分析包括促血管生成细胞因子的免疫分析、组织学损伤分级和斑点血管造影。结果在第0、3、10天时，定量和定性灌注差异均明显。纳米纤维基PDO薄膜可显著改善气管移植段的灌注(P <；. 05)。手术对照组的组织学损伤评分明显低于治疗组(P <；. 01)。免疫分析显示，治疗组血管细胞粘附分子1的表达增加(P <；. 05)。结论应用纳米纤维为基础的PDO薄膜诱导局部组织反应，改善移植气道血流断流模型的灌注和组织学损伤评分。免疫多路复用提示局部炎症反应可能驱动血管生成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

JTCVS open

CiteScore

1.70

自引率

0.00%

发文量