應用波浪狀電紡絲纖維於功能性韌帶組織工程

Abstract

韌帶由平行排列的波浪狀纖維蛋白組成，提供其非線性的機械性質。波浪狀的靜電紡絲可有效模擬天然韌帶組織的纖維蛋白結構與機械功能，並可促進相關細胞基質的基因表現。然而，具有緻密波浪纖維結構的高分子材料於組織工程的應用仍需克服長期細胞與細胞基質分布無法均勻的問題。本研究透過在細胞培養初期將波浪狀纖維結構拉伸的方式，成功改善原先細胞分布不均勻的問題，並且延伸先前實驗室的研究結果，給與人工組織生物化學與力學刺激。我們發現，透過早期材料拉伸配合長期的生物化學性刺激，能夠有效的提高膠原蛋白的生成，成功製成具有均勻細胞與細胞基質與天然韌帶組織非線性機械性質的功能性材料。

Collagen fibers of ligaments and tendons exhibit crimp patterns that contribute to tissue mechanical functionality. In tissue engineering, electrospinning is widely used to generate aligned fibrous material that simulate the collagen fiber bundles. Moreover, aligned wavy fibrous scaffolds can recapitulate the mechanical functionality of the native tissue. The wavy fibers are also cell instructive, promoting ligamentogenic expression profiles. However, inhomogeneous construct development from poor cell infiltration is a significant issue in its application is tissue engineering. We successfully demonstrated that by straightening the wavy fibers with static stretch during initial culture, significant cell infiltration improvement was achieved. We further investigate the long-term effects of biochemical and mechanical stimulation on fibroblast seeded scaffolds. In our study, pre-stretch and sequential growth factor supplementation, led to a more homogeneous wavy fibrous construct with enhanced matrix content in five weeks.