Design of medical tympanostomy conduits with selective fluid transport properties
Design of medical tympanostomy conduits with selective fluid transport properties
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DOI：
10.1126/scitranslmed.add9779
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发表时间：
2023-04-05
影响因子：
17.1
通讯作者：
Remenschneider，Aaron K.
中科院分区：
文献类型：
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作者：
Patel，Haritosh;Pavlichenko，Ida;Remenschneider，Aaron K.
植入式导管、分流器和其他医疗导管对于治疗从耳和眼到脑和肝的各种疾病至关重要，但通常会带来器械感染、阻塞、迁移、功能不可靠和组织损伤的严重风险。缓解这些并发症的努力仍然处于僵局，因为从根本上相互冲突的设计要求：毫米级的尺寸需要最大限度地减少侵入性，但加剧了闭塞和功能障碍。在这里，我们提出了一个合理的设计策略，调和这些权衡在一个植入管，甚至比目前的护理标准更小。使用鼓膜造口管（耳管）作为一个示例性的情况下，我们开发了一种迭代筛选算法，并显示如何独特的弯曲管腔几何形状的液体注入导管可以设计为共同优化药物输送，渗出液引流，防水性，和生物污染/向内生长的预防在一个单一的毛细血管下长度规模的设备。通过广泛的体外研究，我们证明了工程管能够选择性单向和双向液体运输;几乎消除了常见病原菌，血液和细胞的粘附和生长;并防止组织向内生长。与目前的鼓膜造口管相比，工程管还能够实现完整的鼓膜愈合和听力保护，并在健康的龙猫中耳中表现出更有效和快速的抗生素递送，而不会导致长达24周的耳毒性。本文提出的设计原理和优化算法可以使管能够针对广泛的患者需求进行定制。
Implantable tubes, shunts, and other medical conduits are crucial for treating a wide range of conditions from ears and eyes to brain and liver but often impose serious risks of device infection, obstruction, migration, unreliable function, and tissue damage. Efforts to alleviate these complications remain at an impasse because of fundamentally conflicting design requirements: Millimeter-scale size is required to minimize invasiveness but exacerbates occlusion and malfunction. Here, we present a rational design strategy that reconciles these trade-offs in an implantable tube that is even smaller than the current standard of care. Using tympanostomy tubes (ear tubes) as an exemplary case, we developed an iterative screening algorithm and show how unique curved lumen geometries of the liquid-infused conduit can be designed to co-optimize drug delivery, effusion drainage, water resistance, and biocontamination/ingrowth prevention in a single subcapillary–length-scale device. Through extensive in vitro studies, we demonstrate that the engineered tubes enabled selective uni- and bidirectional fluid transport; nearly eliminated adhesion and growth of common pathogenic bacteria, blood, and cells; and prevented tissue ingrowth. The engineered tubes also enabled complete eardrum healing and hearing preservation and exhibited more efficient and rapid antibiotic delivery to the middle ear in healthy chinchillas compared with current tympanostomy tubes, without resulting in ototoxicity at up to 24 weeks. The design principle and optimization algorithm presented here may enable tubes to be customized for a wide range of patient needs.