質傳限制為組織工程仍待突破的一項關鍵技術，在人造組織中預先培養具有生物功能的微血管網路，以輸送養分與排除細胞代謝廢物，防止細胞壞死，是亟待克服的挑戰。實驗顯示在體外培養內皮細胞形成微血管的過程中，細胞遷徙而形成微血管叢，然而現今微血管叢形態生成理論，還無法解釋所有的實驗結果，完整的模型與機轉仍有待確定。本計畫規劃以三年時間完成微血管叢模擬程式及實驗驗證，第一年建立流體剪力導引體外培養微血管叢的生長技術，第二年規劃提出微血管叢生成模型 (vessel plexus formation model) 以修正目前理論模型的缺點。第三年將結合微血管叢生成模型與計算流體力學 (computational fluid dynamics, CFD)，模擬流體剪力導引內皮細胞生成微血管網絡的效應。體外微血管叢培養是極具潛力的研究課題，本計畫發展建立流體剪力導引微血管叢生長的技術，將有助於移植的微血管與人體內動脈與靜脈連接，減少因環境變動所產生的血管重塑，使體外培養的微血管組織在移植入人體後迅速發揮功能。同時對於微血管叢形態發生力學的理論發展，建立組織工程電腦模擬平台，執行實驗參數優化，亦有實質的貢獻。 ;Mass transfer limitation impedes the engineered tissues with no preformed capillary plexus that can be thicker than 2 mm. Pre-vascularization has to be fulfilled before an engineered tissue ready to be implanted into human body. Experiments demonstrated that the endothelial cells transfer their migration behavior via more strong interaction with the environmental substrate and gradually aggregate forming the vascular plexus. To date, the mechanisms underlying the formation of blood vessel plexus from the coalescence and patterning of endothelial cells is still unclear. This research proposal containing three parts aims to conduct the theoretical model development, numerical simulation and experiment verification. All the work will be done in three years. The first part is to build an experimental system that utilize fluid flow to guide the orientation and alignment of the in Vitro capillary plexus. The second part is to develop a novel theoretical vessel plexus formation model that can consist with the biological facts and interpret the mechanisms underlying the vascular plexus formation. The third part is to combine the vascular plexus formation model with computational fluid dynamics to optimize the operating conditions for engineering the capillary plexus formation. The developed technology for guiding the formation of functional capillary plexus in Vitro using fluid shear will decrease the required capillary remodeling time and help the blood vessel bridge between the patients’s and implanted tissues. The developed theoretical model and simulation tool will not only advance the tissue development theory but also help optimize the tissue engineering parameters and operating conditions.
