探討在雙軸的力學環境下人造組織裡產生組織結構的作用機制並建立組織結構與相對應的機械性質的關係

Abstract

組織工程有極大的潛力可提供具正常功能的組織或器官以供移植. 當所欲取代的 組織在體內具備機械方面的功能, 這些植入物的機械性質就非常重要; 他們的機械性 質須能與原來體內的組織相似. 我們提議建造能與非線性光學系統結合的雙軸培養裝 置, 並雙軸往復致動器以供動態拉放凝膠, 及雙軸機械性質測試機以取得凝膠的應力 與應變關係. 我們將使用不含支架之含纖維母細胞之膠原蛋白凝膠或含細胞之纖維蛋 白凝膠作為我們的組織模型. 我們將對凝膠在雙軸力學環境下的組織結構的發展作了 解, 而因組織結構與其機械強度息息相關, 我們也會嘗試建立兩者間之關聯. 因在此二 組織模型下, 胞外間質是由纖維母細胞所調控, 我們相信細胞與胞外間質間的互動關 係對於組織結構的發展有重要的影響. 所以我們會探討造成細胞或纖維方向改變的機 制並檢視在雙軸力學環境下, 凝膠內細胞的移動行為. 這個計畫若能執行成功, 將讓我 們了解一個對力學的負載有反應的人造組織, 其發展中的組織結構與其機械性質的關 係. 更重要的, 我們會對如何操控雙軸的力學環境而使我們的人造組織達到所求之機 械性質有更多的認識.

Tissue engineering has great potential to provide viable, functional tissue/organ for transplantation. If tissues to be replaced have their important mechanical functions in the body, the mechanical properties of the implants are often critical; the mechanical properties of them should match that of the host tissue. We propose to build biaxial culturing chambers, which can be incorporated into nonlinear optical microscopy system for imaging gels, biaxial cyclic actuators, which allow gels to be cyclically stretched, and a biaxial mechanical tester, which measures biaxial stress-strain behaviors of gels. Scaffold-free fibroblasts-seeded collagen or fibrin gels will be served as the model tissues. We propose to study the development of structural organization, which has an important role in mechanical strength of a material, of model tissues under biaxial loading conditions and establish correlation between the mechanical properties and the structural organization. As extracellular matrix is regulated by embedded cells, we propose that the cell-ECM interactions must play a significant role in determination of the structural organization. In particular, we will explore mechanism behind cell/fiber orientations and examine cell migration in gels subjected to biaxial loading. Successful completion of this project will improve our understanding of the relationship between the evolving structural organization and the bulk mechanical properties in load-responsive engineered tissues. More importantly, we will know better how to manipulate biaxial loading conditions to achieve desired mechanical behavior of engineered tissues.