생체 모방형 혈관 네트워크를 이용한 대 체적 조직의 개발

Abstract

Recent advances in tissue engineering and regenerative medicine offer new therapeutic opportunities in the field of medicine. Although engineered-tissues have shown potentials in an experimental stage, only a limited number of tissues such as skin have been successfully regenerated for clinical use. One of the challenges that hamper rapid clinical translation of engineered-tissues is an inadequate oxygen and nutrient supply to the interior parts of a scaffold. This thesis presents construction of engineered-tissue containing effective vascular network to meet the requirements of cells. The research places emphasis on the development of a strategy for designing effective vascular network and improvement of in-vivo applicability. Details on the research are given below.To design an effective fluidic network system based on the understanding of oxygen transport, a method for predicting oxygen transport in engineered-tissue was devised by introducing a time-varying effective diffusion coefficient (De,s). Then fluidic networks were designed and evaluated based on oxygen transport simulation using . The good agreement between experiments and simulation demonstrated the reliability of the design procedure.Rapid endothelization methods were developed to create an anti-thrombogenic surface in fluidic networks by mimicking a natural vessel wall. Experimental results showed that a transient increase of shear stress at an appropriate time is a key to the enhancement of endothelization. Moreover, surface modification with bioactive materials, such as collagen and recombinant MAP-RGD, exerted a synergistic effect with the shear stress preconditioning.To realize the design and endothelized surface of a vascular network in a porous scaffold, indirect-microstereolithgraphy (MSTL) technology was applied in the process of scaffolds fabrication. The high resolution (up to several tens of microns) of MSTL allowed the construction of precise and complex fluidic networks in a porous scaffold. This process can be used to fabricate not only 2D fluidic networks, but also 3D fluidic networks without further modifications. And, by adapting hydrogel coating in the fabrication process, hydrogel barrier was layered on the luminal surface of the fluidic network. The hydrogel barrier made it possible to line endothelial cells on the luminal surface. Finally, engineered-tissue containing a vascular network was constructed successfully. The approach attempted in this research will bring the regeneration of large-scale multicellular organism and dense tissue mimics closer to reality for in-vitro and in-vivo applications. Moreover each technology developed in this research can be applied various areas in tissue engineering and regenerative medicine.