Fabrication of three-dimensional hydrogel scaffolds for modeling shunt failure by tissue obstruction in hydrocephalus.
Fabrication of three-dimensional hydrogel scaffolds for modeling shunt failure by tissue obstruction in hydrocephalus.
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DOI：
10.1186/s12987-015-0023-9
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发表时间：
2015-11-14
影响因子：
7.3
通讯作者：
Shain W
中科院分区：
文献类型：
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作者：
Harris C;Pearson K;Hadley K;Zhu S;Browd S;Hanak BW;Shain W
脑积水治疗中的分流梗阻知之甚少，是多因素的，并且在许多情况下建模无效。几种机制可能是负责的，其中之一涉及分流渗透反应细胞从脑实质。这尚未在培养物中建模，并且在没有大样本量的情况下无法在体内一致地检查。我们开发并测试了星形胶质细胞在临床级脑室导管周围迁移和增殖并进入导管孔的三维体外模型，该模型模拟了可能导致分流阻塞的实质细胞生长的发展。在分流导管上观察到细胞附着和生长长达80天，直至51天，存活率至少为77%。该模型可用于研究静态和脉动流条件下脑室导管的细胞附着，这更好地模拟了生理脑脊液动力学和分流系统流速（0.25 mL/min，100脉冲/min）。通过脑室导管的脉动流在18小时后使细胞附着/生长降低63%。在这两种情况下，都可以观察到分流导管孔周围和孔内的细胞积聚。单独或与先前发表的分流阻塞培养模型组合，该模型用作相关试验床，以分析分流失败的机制，并测试将防止细胞附着和生长的导管修改。
Shunt obstruction in the treatment of hydrocephalus is poorly understood, is multi-factorial, and in many cases is modeled ineffectively. Several mechanisms may be responsible, one of which involves shunt infiltration by reactive cells from the brain parenchyma. This has not been modeled in culture and cannot be consistently examined in vivo without a large sample size. We have developed and tested a three-dimensional in vitro model of astrocyte migration and proliferation around clinical grade ventricular catheters and into catheter holes that mimics the development of cellular outgrowth from the parenchyma that may contribute to shunt obstruction. Cell attachment and growth was observed on shunt catheters for as long as 80 days with at least 77 % viability until 51 days. The model can be used to study cellular attachment to ventricular catheters under both static and pulsatile flow conditions, which better mimic physiological cerebrospinal fluid dynamics and shunt system flow rates (0.25 mL/min, 100 pulses/min). Pulsatile flow through the ventricular catheter decreased cell attachment/growth by 63 % after 18 h. Under both conditions it was possible to observe cells accumulating around and in shunt catheter holes. Alone or in combination with previously-published culture models of shunt obstruction, this model serves as a relevant test bed to analyze mechanisms of shunt failure and to test catheter modifications that will prevent cell attachment and growth.