| 摘要: | 根據世界衛生組織(World Health Organization, WHO)在 2022 年 3 月所發布的聽力統計表明，現今全球有近5億的人口患有聽力受損(Hearing Loss)這項疾病，而在2050年時患病人口數將會成長到10億左右，原因在於各國科技的快速發展及醫療水平逐漸提升，導致全球人口的平均壽命延長並且步入高齡化社會(Aging Society)，同時針對於人類的感覺器官來說，聽覺的衰退是最為快速，若情況嚴重甚至會影響與人進行社交的能力，因此需要即刻提出有效的治療方案，依聽損症狀主要可以分為三大類，分別是:傳導型聽損(Conductive Hearing Loss)、感音神經型聽損Sensorineural Hearing Loss)及混和型聽損(Mixed Hearing Loss)，其中又以感音神經型聽損為最大宗，約佔有8成左右的比例，造成該聽損的可能原因是長期處在高分貝的噪音環境、服用具有耳毒性的藥物、遺傳、老化、病毒等種種因素，進而破壞位處內耳深處的聽毛細胞(Inner Ear Hair Cell)，通常對哺乳動物(Mammal)的聽毛細胞造成的損傷是屬於不可逆的，目前所使用的治療方案為助聽器(Hearing Aids)及人工電子耳(Cochlear Implants)等醫療輔具來維持基本的聽力行為，而在藥物治療的部分目前仍在進行臨床試驗還無法實際應用於聽損治療。在本研究中，我們將探討三個主要方面，分別為細胞在動靜態環境下進行三維耳蝸細胞成熟化的細胞培養、仿生耳蝸的影像重構及3D列印，以及最終的新型體外耳蝸
模型。 在第一部分，我們以細胞培養為實驗的主軸。本研究以P0~P2的初生鼠為主要研究對象，許多文獻指出新生哺乳動物的耳蝸細胞具有再生能力，通常這種能力會隨著出生時間的增加而急劇下降，在出生後的三天至一周內即消失，因此我們希望透過這樣的方式，提取具有再生能力的耳蝸細胞，並且結合生物3D列印技術，將這些細胞混入生物墨水中進行列印，提供三維培養環境之外添加適當的培養基EFICVP6來促進細胞增生，以及分化試劑LYC進行耳蝸細胞的成熟化，以成功在體外重新分化出新生的聽毛細胞(Hair Cell)。第二部分將以耳蝸影像重構為主要研究核心，耳蝸內部結構相對複雜，目前尚無比較完整的體外耳蝸模型，且臨床實驗多半以豬隻或老鼠為練習對象，但在個體及耳蝸顯微結構上仍存在顯著差異，同時在手術中醫師難以確認電子耳實際穿入的位置及是否對耳蝸內部造成損傷，影響內耳治療的準確性和安全性。因此，本研究希望透過影像重建結合3D列印，能夠完整復刻出新型體外耳蝸模型，以提高手術準確性和安全性。第三部分將會整合前兩部分，進行耳蝸及電子耳的影像重構。主要目的是提供耳科醫師更完整的手術練習模型，同時在電子耳上搭載治療內耳的藥物，隨後，將搭載藥物的電子耳進行穿入的動作，模擬手術實際穿入過程，這樣的配套措施不但成為內耳治療藥物篩選模型，也能為未來聽損治療相關研究提供更完整的研究方案。;According to the World Health Organization (WHO) statistics released in March 2022,nearly 500 million people worldwide suffer from hearing loss. By 2050, this number is expected to grow to around 1 billion due to the rapid development of technology and the gradual improvement of medical standards, which have led to an increase in global life expectancy and an aging society. Hearing decline is the most rapid among human sensory organs, and severe cases can affect the ability to socialize, necessitating the immediate proposal of effective treatment plans. Hearing loss symptoms can be divided into three main categories: conductive hearing loss, sensorineural hearing loss, and mixed hearing loss.
Sensorineural hearing loss is the most prevalent, accounting for about 80% of cases. Possible causes include long-term exposure to high-decibel noise, use of ototoxic drugs, genetics, aging, and viruses, which can damage the inner ear hair cells. Damage to these cells in mammals is usually irreversible. Current treatments include the use of hearing aids and cochlear implants to maintain basic hearing functions, while pharmaceutical treatments are still undergoing clinical trials and cannot yet be practically applied to hearing loss treatment. This study will explore three main aspects: three-dimensional cochlear cell maturation in dynamic and static environments, image reconstruction and 3D printing of a bionic cochlea,
and the development of a novel in vitro cochlear model.
In the first part, the focus is on cell culture experiments. This research uses newborn mice (P0-P2) as the main subjects. Literature indicates that cochlear cells of newborn mammals possess regenerative abilities, which typically diminish rapidly with age, disappearing within three days to a week after birth. Therefore, we aim to extract cochlear cells with regenerative capabilities and use bio-3D printing technology to mix these cells into
bio-ink for printing, providing a three-dimensional culture environment. We will add appropriate culture media, EFICVP6, to promote cell proliferation, and differentiation reagent
LYC for cochlear cell maturation, successfully differentiating new hair cells in vitro. The second part focuses on cochlear image reconstruction. The internal structure of the cochlea is relatively complex, and currently, there is no complete in vitro cochlear model.
Clinical experiments often use pigs or mice as practice subjects, but significant differences exist in individual and cochlear microstructures. During surgery, it is challenging for physicians to confirm the actual position of the cochlear implant and whether it causes internal cochlear damage, affecting the accuracy and safety of inner ear treatments. Therefore, this study aims to create a new in vitro cochlear model through image reconstruction
combined with 3D printing, improving surgical accuracy and safety. The third part will integrate the first two parts, focusing on cochlear and cochlear implant image reconstruction. The main goal is to provide otologists with a more complete surgical practice model. Additionally, we aim to load therapeutic drugs for inner ear treatment
onto the cochlear implant. Subsequently, the drug-loaded cochlear implant will be inserted to simulate the surgical insertion process. This approach serves as a drug screening model for inner ear treatment and provides a more comprehensive research plan for future hearing loss
treatment research. |
