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在人体中使用体内生物反应器技术进行生物工程化隆突重建:概念验证研究。

Bioengineered carina reconstruction using In-Vivo Bioreactor technique in human: proof of concept study.

作者信息

Xu Yuanyuan, Guo Zhiyi, Liu Ruijun, Wang Hongwu, Wang Sheng, Weder Walter, Pan Yingen, Wu Jingxiang, Zhao Heng, Luo Qingquan, Tan Qiang

机构信息

Shanghai Lung Cancer Center, Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China.

Department of Pulmonary Medicine, Emergency General Hospital, Beijing, China.

出版信息

Transl Lung Cancer Res. 2020 Jun;9(3):705-712. doi: 10.21037/tlcr-20-534.

DOI:10.21037/tlcr-20-534
PMID:32676332
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7354144/
Abstract

BACKGROUNDS

Long-segment airway defect reconstruction, especially when carina is invaded, remains a challenge in clinical setting. Previous attempts at bioengineered carina reconstruction failed within 90 days due to delayed revascularization and recurrent infection.

METHODS

To establish the feasibility of carina bioengineering use In-Vivo Bioreactor technique. Uncontrolled single-center cohort study including three patients with long-segment airway lesions invading carina. Radical resection of the lesions was performed using standard surgical techniques. After resection, In-Vivo Bioreactor airway reconstruction was performed using a nitinol stent wrapped in two layers of acellularized dermis matrix (ADM). Two Port-a-Cath catheters connected to two portable peristaltic pumps were inserted between the ADM layers. The implanted bioengineered airway was continuously perfused with an antibiotic solution via the pump system. Peripheral total nucleated cells (TNCs) were harvested and seeded into the airway substitute via a Port-a-Cath twice a week for 1 month. The patients were treated as a bioreactor for in situ regeneration of their own bioengineered airway substitute.

RESULTS

Three patients were included in the study (mean age, 54.7 years). The first patient underwent 8 cm long trachea and carina reconstruction, the second patient 6 cm long trachea, carina and main bronchus reconstruction. The third patient right main bronchus and carina reconstruction. Major morbidity included gastric retention and pneumonia. All three patients survived till last follow-up and bronchoscopy follow-up showed well-vascularized regenerated tissue without leakage.

CONCLUSIONS

In this uncontrolled study, In-Vivo Bioreactor technique demonstrated potential to be applied for long-segment trachea, carina and bronchi reconstruction. Further research is needed to assess efficacy and safety.

摘要

背景

长节段气道缺损重建,尤其是隆突受侵时,在临床环境中仍是一项挑战。先前生物工程化隆突重建的尝试在90天内失败,原因是血管再生延迟和反复感染。

方法

为确定使用体内生物反应器技术进行隆突生物工程的可行性。进行了一项非对照单中心队列研究,纳入3例长节段气道病变侵犯隆突的患者。采用标准手术技术对病变进行根治性切除。切除后,使用包裹在两层脱细胞真皮基质(ADM)中的镍钛诺支架进行体内生物反应器气道重建。两根连接到两个便携式蠕动泵的植入式静脉输液港导管插入ADM层之间。通过泵系统向植入的生物工程气道持续灌注抗生素溶液。每周两次通过植入式静脉输液港采集外周全核细胞(TNCs)并接种到气道替代物中,持续1个月。将患者作为生物反应器用于自身生物工程气道替代物的原位再生。

结果

3例患者纳入研究(平均年龄54.7岁)。第1例患者接受了8 cm长气管和隆突重建,第2例患者接受了6 cm长气管、隆突和主支气管重建。第3例患者接受了右主支气管和隆突重建。主要并发症包括胃潴留和肺炎。所有3例患者均存活至最后一次随访,支气管镜检查随访显示再生组织血管化良好且无渗漏。

结论

在这项非对照研究中,体内生物反应器技术显示出可用于长节段气管、隆突和支气管重建的潜力。需要进一步研究以评估其疗效和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0b5/7354144/90a7234476a5/tlcr-09-03-705-vid2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0b5/7354144/dc42dd6f54bd/tlcr-09-03-705-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0b5/7354144/82a37ece8a5d/tlcr-09-03-705-vid1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0b5/7354144/90a7234476a5/tlcr-09-03-705-vid2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0b5/7354144/dc42dd6f54bd/tlcr-09-03-705-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0b5/7354144/82a37ece8a5d/tlcr-09-03-705-vid1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0b5/7354144/90a7234476a5/tlcr-09-03-705-vid2.jpg

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