Oral mucositis on a chip: modeling induction by chemo- and radiation treatments and recovery.
Oral mucositis on a chip: modeling induction by chemo- and radiation treatments and recovery.
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DOI：
10.1088/1758-5090/ac933b
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发表时间：
2022-10-27
期刊：
影响因子：
9
通讯作者：
Raub, Christopher B.
中科院分区：
文献类型：
--
作者：
Ly, Khanh L.;Luo, Xiaolong;Raub, Christopher B.
关键词：
口腔粘膜炎（OM）是一种使人衰弱的并发症，影响大约70%接受化疗和/或放疗的头颈癌患者。目前还没有广泛有效的OM预防治疗方法。因此，在体外模型的癌症治疗诱导OM将有助于研究可能的起源的病理和未来的药物靶点，以改善it. In这项研究中，我们提出了一种微流体口腔粘膜triculture组织结构组成的角质形成细胞层连接到上皮下成纤维细胞和内皮细胞包埋的胶原凝胶。为了解决微流体中粘膜构建体的典型低稳定性，实施了氯铵催化的光交联以增强胶原凝胶并防止角质形成细胞的侵入，从而维持组织构建体的几何形状和口腔粘膜屏障功能超过18天的培养。接下来，OM芯片暴露于顺铂（第10天）和损伤性辐射（第11天，第10天+/-顺铂），模拟癌症治疗的损伤。在第11-18天观察到组织层和功能的损伤，然后恢复。因此，在微流体培养中模拟了口腔粘膜炎诱导和消退的几个重要特征。芯片上的口腔粘膜炎模型允许对OM的机制和潜在的治疗进行更复杂的研究。口腔粘膜炎是癌症治疗的严重副作用，治疗选择有限。人牙龈角质形成细胞，成纤维细胞，和微真皮血管内皮细胞在微流控芯片的三代培养代表了一个平台，以测试诱导和解决粘膜炎。顺铂和放射治疗对粘膜结构造成损伤，随后恢复。
Oral mucositis (OM) is a debilitating complication affecting roughly 70% of head and neck cancer patients receiving chemotherapy and/or radiation treatment. No broadly effective preventative treatment for OM exists. Therefore, an in vitro model of cancer treatment-induced OM would aid studies into possible origins of the pathology and future drug targets to ameliorate it. In this study, we present a microfluidic oral mucosa triculture tissue construct consisting of a keratinocyte layer attached to a subepithelial fibroblast and endothelial cell-embedded collagen gel. To address the typically low stability of mucosal constructs in microfluidics, ruthenium-catalyzed photocrosslinking was implemented to strengthen the collagen gel and prevent the invasion of kerotinacytes, thus maintaining tissue construct geometry and oral mucosa barrier function for over 18 days of culture. Next, the OM chip was exposed to cisplatin (day 10) and damaging radiation (day 11, +/−cisplatin at day 10), mimicking damage from cancer therapy. Damage to and then recovery of the tissue layers and function were observed over days 11–18. Therefore, several important features of oral mucositis induction and resolution were modeled in microfluidic culture. The oral mucositis model on a chip allows for more sophisticated studies into mechanisms of OM and potential treatments. Oral mucositis is a serious side effect of cancer therapy with limited treatment options. A triculture of human gingival keratinocytes, fibroblasts, and microdermal vascular endothelial cells in a microfluidic chip represents a platform to test the induction and resolution of mucositis. Cisplatin and radiation treaments cause damage to the mucosa constructs, followed by recovery.
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DOI：
10.3390/s17071603
发表时间：
2017-07-10
期刊：
Sensors (Basel, Switzerland)
影响因子：
--
作者：
Bunge F;Driesche SVD;Vellekoop MJ
通讯作者：
Vellekoop MJ
在药物发现的边界，片上的器官。
DOI：
10.1038/nrd4539
发表时间：
2015-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Esch EW;Bahinski A;Huh D
通讯作者：
Huh D
影响因子：
19
作者：
Agarwal A;Farouz Y;Nesmith AP;Deravi LF;McCain ML;Parker KK
通讯作者：
Parker KK
影响因子：
5.6
作者：
Cinausero M;Aprile G;Ermacora P;Basile D;Vitale MG;Fanotto V;Parisi G;Calvetti L;Sonis ST
通讯作者：
Sonis ST
影响因子：
14
作者：
Elvin, Christopher M.;Brownlee, Alan G.;Werkmeister, Jerome A.
通讯作者：
Werkmeister, Jerome A.