Mouse Model of Tracheal Replacement With Electrospun Nanofiber Scaffolds
Mouse Model of Tracheal Replacement With Electrospun Nanofiber Scaffolds
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DOI：
10.1177/0003489419826134
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发表时间：
2019-05-01
影响因子：
1.4
通讯作者：
Chiang, Tendy
中科院分区：
文献类型：
--
作者：
Dharmadhikari, Sayali;Best, Cameron A.;Chiang, Tendy
目的：组织工程气管移植物（TETG）的临床经验充满了移植物狭窄和延迟上皮化。原位置换，概括的临床研究结果的小鼠模型，将有利于移植物stenosis. Methods的细胞和分子机制的研究：静电纺丝气管支架创建使用nonresorbable（聚对苯二甲酸乙二醇酯+聚氨酯）和共静电纺丝可吸收（聚乳酸-共-己内酯/聚乙醇酸）聚合物（n = 10/组）。进行生物力学测试，以比较植入支架与天然小鼠气管的载荷位移。小鼠接受同基因移植物（n = 5）和不可吸收（n = 10）和可吸收（n = 10）支架的原位气管置换术。使用苏木精和伊红（H & E）评估吻合处的组织，借助于免疫荧光测试评估K5+基底细胞，并量化支架的细胞浸润。显微计算机断层扫描进行评估移植通畅性和相关的放射学和组织学研究结果与呼吸symptoms.Results：合成支架在压缩试验中的超生理相比，本地小鼠气管（P <.0001）。不可吸收支架比可吸收支架更硬（P = 0.0004）。80%的同基因受体存活到术后60天的研究终点。不可吸收支架的平均生存期为11.40 +/-7.31天，可吸收支架的平均生存期为6.70 +/-3.95天（P = 0.095）。狭窄表现为不可吸收支架中的组织过度生长和可吸收支架中的软化。支架细胞浸润的定量与可吸收支架中的存活时间相关（R-2 = 0.95，P = 0.0051）。显微计算机断层扫描显示移植物远端吻合口在第5天发生狭窄，并持续至第11天处死。结论：人工气管支架原位移植术后移植物狭窄可在小鼠体内形成。广泛的谱系追踪和转基因小鼠模型将允许未来的研究TETG狭窄的细胞和分子机制。
Objectives: The clinical experience with tissue-engineered tracheal grafts (TETGs) has been fraught with graft stenosis and delayed epithelialization. A mouse model of orthotopic replacement that recapitulates the clinical findings would facilitate the study of the cellular and molecular mechanisms underlying graft stenosis.Methods: Electrospun nanofiber tracheal scaffolds were created using nonresorbable (polyethylene terephthalate + polyurethane) and co-electrospun resorbable (polylactide-co-caprolactone/polyglycolic acid) polymers (n = 10/group). Biomechanical testing was performed to compare load displacement of nanofiber scaffolds to native mouse tracheas. Mice underwent orthotopic tracheal replacement with syngeneic grafts (n = 5) and nonresorbable (n = 10) and resorbable (n = 10) scaffolds. Tissue at the anastomosis was evaluated using hematoxylin and eosin (H&E), K5+ basal cells were evaluated with the help of immunofluorescence testing, and cellular infiltration of the scaffold was quantified. Micro computed tomography was performed to assess graft patency and correlate radiographic and histologic findings with respiratory symptoms.Results: Synthetic scaffolds were supraphysiologic in compression tests compared to native mouse trachea (P < .0001). Nonresorbable scaffolds were stiffer than resorbable scaffolds (P = .0004). Eighty percent of syngeneic recipients survived to the study endpoint of 60 days postoperatively. Mean survival with nonresorbable scaffolds was 11.40 +/- 7.31 days and 6.70 +/- 3.95 days with resorbable scaffolds (P = .095). Stenosis manifested with tissue overgrowth in nonresorbable scaffolds and malacia in resorbable scaffolds. Quantification of scaffold cellular infiltration correlated with length of survival in resorbable scaffolds (R-2 = 0.95, P = .0051). Micro computed tomography demonstrated the development of graft stenosis at the distal anastomosis on day 5 and progressed until euthanasia was performed on day 11.Conclusion: Graft stenosis seen in orthotopic tracheal replacement with synthetic tracheal scaffolds can be modeled in mice. The wide array of lineage tracing and transgenic mouse models available will permit future investigation of the cellular and molecular mechanisms underlying TETG stenosis.