2011-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/655887摘要：軟骨組織工程是近年許多再生醫學研究的方向，為了達到最佳的功能性，瓊脂糖(agarose)所做出的人工軟骨之機械性質最接近天然的關節軟骨，其他材料尚未能達到類似的功能性，但是目前並不了解瓊脂糖為何可以幫助軟骨生長。在與哥倫比亞大學的Dr. Vunjak-Novakovic 及塔夫茲大學的Dr. David Kaplan合作下，我們之前發展了新的可包埋活細胞的絲水膠製備法，並加入了原代軟骨細胞，生產出媲美瓊脂糖的人工軟骨。此結果已發表於期刊，並取得美國國家衛生研究院(NIH)的經費來研發絲水膠在化學性質上的最佳化。此外本人在台灣新成立的實驗室正開發一種新的包括矽膠的支架的三維複合結構，能精確地控制三維水膠的力學性能，卻不改變其化學性質。基於這些發展，本計畫的目標即為研究細胞的力學環境對軟骨組織的發展的影響。雖然有些研究已開始探討三維支架剛度對細胞行為的影響，但大部分的實驗都以改變水凝膠的濃度或交聯程度來達到機械性能的變化，從而也改變其化學和擴散性質。本系統並可將原代軟骨細胞種植在絲水膠之內部或表面，以了解細胞在2D或3D環境下的不同表現。本計畫利用微製程和材料工程的最新進展，以達到對生物物理、細胞調節和再生醫學的新的了解。<br> Abstract: Tissue engineering has been widely studied as a treatment option for the repair of cartilage injury/degeneration. To achieve optimal tissue functionality, agarose has been a particularly successful material for cartilage, yielding constructs with functional properties approaching those of native articular cartilage. Other materials have not resulted in constructs with comparable functional properties and it is not understood which specific characteristics of agarose contribute to its superior functionality. Recently, a new variation of silk hydrogel became available that allowed cell encapsulation with the full maintenance of cell viability. In collaboration with Dr. Vunjak-Novakovic of Columbia University, we encapsulated primary chondrocytes into this hydrogel and found one particular preparation that resulted in excellent mechanical properties of engineered cartilage. For the first time, another material, silk hydrogel, produced functional properties of engineered cartilage comparable to those achieved with agarose. Based on this exciting result, we have obtained funding from the National Institute of Health for the optimization of bulk silk hydrogel properties such as crosslinking and concentration for cartilage functional tissue engineering. Silk fibroin, being a naturally occurring protein, offers many potentials of modification and provides us with extraordinary possibilities not only to optimize construct growth, but also to understand how some hydrogels are ‘better’ scaffolding materials. With the new lab in Taiwan, we have developed a novel technology of a 3D composite material with a silicon elastomer support structure to allow precise control of 3D hydrogel mechanical properties with identical chemical and diffusional characteristics. Encouraged by these developments, we propose the current project with a central hypothesis that optimal cartilage tissue development requires appropriate scaffold mechanical integrity mediated via cell attachment. The overall goal of this project is to delineate the effects of the mechanical properties of the cell microenvironment on cartilage tissue development. While a number of studies have examined the effect of 3D scaffold stiffness on cell behaviors, most of the experiments have changed the degree of cross-linking or hydrogel concentration to achieve changes in mechanical properties, thus changing also the chemical and diffusional properties. Taking advantage of the low cost and high spatial resolution of soft lithography, we will develop the 3D composite material of silk hydrogel and silicon elastomer using microfabrication. Primary chondrocytes can then be seeded either within the silk hydrogel or on top, thus allowing 3D or 2D study of parameters. Advances in microfabrication and silk material engineering allow for this novel application of new understanding in biophysical cell phenotypic regulation as well as improvement in regenerative medicine.軟骨組織工程生物材料複合材料絲蛋白膠原蛋白Cartilage tissue engineeringbiomaterialscomposite materialssilk fibroincollagen