2020-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/686942摘要：眼角膜移植需由人體捐贈已供不應求。以3D列印方式製作人造眼角膜，不僅容易 製造且客製化患者需求，提供更好的服務。然角膜的組織複雜包含交錯的膠原蛋白 纖維，增加仿生製造和力學分析的困難。目前，角膜的力學參數都由巨觀實驗成果 回歸獲得;但因控制變數太多，以致很多重要力學參數無法容易純化萃取獲得。故 醫療儀器廠商提出許多取代性的生物力學參數，以輔助量測;然不幸地，迄今這些 廠商提供的力學參數，在臨床診斷上仍無較具公認性的參考指標性價值。本提案延 續前期角膜力學分析技術，將其探討尺度縮小到細胞，以更細膩地角度重新檢討組 織間力學和組織與人造支架間的交互關係。配合總計畫，人工角膜將全角膜由人造 矽水膠，精進至半人造支架與半細胞組織的混生狀態。本計畫之重要性在於透過細 胞力學建立正確角膜組成律模型，奠定人造角膜的力學基礎。計畫將以細胞力學觀 點出發，首先建構基質層細胞的張拉整體(tensegrity)的結構模型，再透過結構力學 模擬單一細胞的成長和群細胞間的行為。張拉整體模型是根據高倍放大基層細胞內 組織圖建構，以壓縮管模擬細胞中微管，和張力索模擬拉伸微絲和中間絲。拉伸微 絲，中間絲，壓縮微管呈現互補的預力平衡態，便如同預力桿件間的彼此平衡系統 ;近一步地，若桿件力的超額，即代表細胞間壅擠與邁向衰亡。藉此模型探討基質 層細胞在何種外力環境有利生存，和何應力下抓牢四周支架，用以模擬角膜細胞與 支架間應力。細胞實驗的部分由台大醫學院協助負責，人造支架將與其他子計畫合 作取得3D列印原型。本子計畫以原子力顯微鏡的探針操控技術，以探針觸摸基質 層細胞獲取測量數據;更進一步，建立相關細胞力學的結構分析，和角膜支架的最 適化設計。<br> Abstract: Corneal transplantation needs donated corneas which are always shortage. An artificial cornea made by 3D printing can not only make easy but be customized to satisfy patient demand. It provides better services. But corneal tissues containing directional collagen fibers leads the difficulty of this corneal bio- fabrication and development of biomechanics. Currently, most cornea mechanical parameters are obtained by regression from experimental results; but too many controlling parameters lead important mechanical parameters not clear and cannot be proved independently. Therefore, the medical and material manufacturers provide similar “biomechanical parameters” to represent the material properties. Unfortunately, these parameters have less recognized helps from clinic diagnosis point of view. This proposal continues the applicant’s early knowledge and experience, and it expands global analysis to local, cytomechanical, study. And it discusses details of tissue mechanics and relationship between tissue and corneal scaffold. With the major project, this proposal improves article cornea from the entire corneal synthetic silicone glue to semi-artifical scaffolds and half-cell tissue mixed state. The significance of this proposal lies in establishing an accurate constative-law model of cornea through cytomechanics, and it helps setup the solid background knowledge of the artificial cornea. From the cytomechanical viewpoint, it provides a tensegrity structure model to simulate the stroma tissue, and then the model helps to simulate cell growing/population and to simulate interaction of group cells. Here the tensegrity model is constructed from the recordings of high quality photos taken from optical microscopy, and it simulates the stretching microfilament, intermediate silk, and compressed microtubules. The balance is existed among stretching microfilament, intermediate silk, and compressed microtubules; and, similarly, the balance is like force balance among members in the tensegrity structure. Furthermore, the overload in members represents the space full and leads cell to die. According to this model, we may predict which underlying stroma cells survive well under certain external environment and circumstances, and we may estimate the forces between the stromal cells and the scaffold. Here the cellular experiment is supported by National Taiwan University Medical college, and the scaffold prototype made by 3D printer is cooperated with other subproject teams. Our group has the atomic force microscopy to help to measure and realize cytomechanical testing. Moreover, it helps to develop cytomechanical analysis and helps to optimize design in scaffold.張拉整體結構角膜細胞力學基質層最適化支架tensegritycytomechanicsstromaoptimizationscaffold