| The loss of organ or tissue is one of the most frequent, devastating and costly problems in human health care. Tissue engineering as one of the innovative biomedical technologies has echoed widely concerns for achieving the goals of harvesting human tissues in-vitro cultivation.Through remodeling the in-vitro biological substitutes which are competence of similar functions of human tissue, tissue engineering give a novel solution to overcome the problems like immunological rejection and lack of donor in xenogenic organ transplantation. However, most of the existing methods can only adchieve simple tissues with no significant structure. There are still some chanllenges on the way to fabricate heterogeneous composite tissues with characteristic micro-scaled structures. This dissertation focuses on the fabrication method to build the functional biological substitute which has similar outer shape and microstructural feature to remodel the working principle of human tissues. The proposed method achieves bottom-up assembly of 3D cellular microstructure based on the coordination among multi microrobots. Through multi-scaled motion and automated cooperation in the microrobotic system, the assembled structure can achieve the composite articifial substitute with similar shape and inner structure of human tissue. It also provide new concept to construct cellular microstructure under 200?m scale, which has biological significance in tissue engineering and provides a paradigm for the fussion of micro-nano robotics and biomedical science. The main research issues and results are summarized as follows.Firstly, considering of current issues in tissue engineering to construct functional 3D cellular structure combining with specific outer shape and microstructural features, we set up a rail-guided multi-microrobotic system to fabricate the microstructure, especially the microvascular-like structures for the inner circulation of tissues. Through the combination of rail sub-system, micromanipulation sub-system and vision feedback sub-system, the proposed method can achieve the automated coordination among multi probes for the cell assembly, which ensures the efficiency and accuracy during the fabrication of in-vitro tissues.Secondly, according to the bottom-up assembly principle of 3D cellular microstructure, we develop an on-chip fabrication method of 2D cellular modules as the assembly units. Through the UV-exposure of crosslinkable hydrogel which mixed with cells in the microfluidic channel, the arbitrary designed shape of 2D modules can be fabricated and the surrounding cells are embedded into the structure simultaneously for the following assembly.Thirdly, in the micro-scaled image, the low contrast of occlusion region shows no distinct intensity between the end-effector and its surroundings, it is difficult to acquire the edge information of end-effector and extract it from background. We propose a novel image process algorithm to achieve the reconstruction of end-effector contour during occlusion based on line fitting and corner detection. To realize the continuous tracking of multi probes which have similar image features, we combining the level set method and particle filtering and send back the position information of every probe tip for the motion control.Finally, the proposed methods in this dissertation are verified by the assembly of cell-embedded vascular-like microtube.we evaluate the robustness and accuracy of image process algorithm for the tracking of multi probe in 3D space under different microscope observation parameters. Through the automated assembly of vascular-like microtube, we verify the effectiveness of the method to assemble cellular microstructure with multi-microrobotic coordinated manipulation. The assembly efficiency and stability is acceptable, which means this method is desirable for the cell assembly and can be used in the future to build more complicated biological substitute for the biomedical application in tissue engineering.
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