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3D 打印微针原位精确刺穿人圆窗膜。

3D-Printed Microneedles Create Precise Perforations in Human Round Window Membrane in Situ.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Columbia University Vagelos College of Physicians and Surgeons.

Department of Mechanical Engineering, Columbia University, New York, New York.

出版信息

Otol Neurotol. 2020 Feb;41(2):277-284. doi: 10.1097/MAO.0000000000002480.

Abstract

HYPOTHESIS

Three-dimensional (3D)-printed microneedles can create precise holes on the scale of micrometers in the human round window membrane (HRWM).

BACKGROUND

An intact round window membrane is a barrier to delivery of therapeutic and diagnostic agents into the inner ear. Microperforation of the guinea pig round window membrane has been shown to overcome this barrier by enhancing diffusion 35-fold. In humans, the challenge is to design a microneedle that can precisely perforate the thicker HRWM without damage.

METHODS

Based on the thickness and mechanical properties of the HRWM, two microneedle designs were 3D-printed to perforate the HRWM from fresh frozen temporal bones in situ (n = 18 total perforations), simultaneously measuring force and displacement. Perforations were analyzed using confocal microscopy; microneedles were examined for deformity using scanning electron microscopy.

RESULTS

HRWM thickness was determined to be 60.1 ± 14.6 (SD) μm. Microneedles separated the collagen fibers and created slit-shaped perforations with the major axis equal to the microneedle shaft diameter. Microneedles needed to be displaced only minimally after making initial contact with the RWM to create a complete perforation, thus avoiding damage to intracochlear structures. The microneedles were durable and intact after use.

CONCLUSION

3D-printed microneedles can create precise perforations in the HRWM without damaging intracochlear structures. As such, they have many potential applications ranging from aspiration of cochlear fluids using a lumenized needle for diagnosis and creating portals for therapeutic delivery into the inner ear.

摘要

假设

三维(3D)打印微针可以在人圆窗膜(HRWM)上产生精确到微米级的小孔。

背景

完整的圆窗膜是将治疗剂和诊断剂递送到内耳的障碍。已经证明,豚鼠圆窗膜的微穿孔通过将扩散增强 35 倍来克服这一障碍。在人类中,挑战在于设计一种能够精确穿孔较厚的 HRWM 而不造成损伤的微针。

方法

根据 HRWM 的厚度和机械性能,设计了两种微针进行 3D 打印,以便从新鲜冷冻的颞骨原位刺穿 HRWM(总共 18 个穿孔),同时测量力和位移。使用共聚焦显微镜分析穿孔;使用扫描电子显微镜检查微针的变形。

结果

HRWM 厚度确定为 60.1 ± 14.6(SD)μm。微针分离了胶原蛋白纤维,并形成了与微针轴直径相等的狭缝状穿孔。微针在与 RWM 初次接触后只需轻微移动即可完成穿孔,从而避免对内耳结构造成损伤。微针在使用后仍然耐用且完整。

结论

3D 打印微针可以在不损伤内耳结构的情况下在 HRWM 上精确穿孔。因此,它们具有许多潜在的应用,从使用内腔针抽吸耳蜗液进行诊断到为内耳道内的治疗药物输送创建门户。

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本文引用的文献

2
In-vitro perforation of the round window membrane via direct 3-D printed microneedles.
Biomed Microdevices. 2018 Jun 8;20(2):47. doi: 10.1007/s10544-018-0287-3.
4
Serrated needle design facilitates precise round window membrane perforation.
J Biomed Mater Res A. 2016 Jul;104(7):1633-7. doi: 10.1002/jbm.a.35692. Epub 2016 Mar 11.
5
A dual wedge microneedle for sampling of perilymph solution via round window membrane.
Biomed Microdevices. 2016 Apr;18(2):24. doi: 10.1007/s10544-016-0046-2.
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Silver/silver chloride microneedles can detect penetration through the round window membrane.
J Biomed Mater Res B Appl Biomater. 2017 Feb;105(2):307-311. doi: 10.1002/jbm.b.33557. Epub 2015 Oct 27.
8
Microperforations significantly enhance diffusion across round window membrane.
Otol Neurotol. 2015 Apr;36(4):694-700. doi: 10.1097/MAO.0000000000000629.

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