Abstract
Precise delivery of targeted cells through magnetically driven microrobots/carriers represents a promising technique for targeted therapy and tissue regeneration. Microrobots actuated by a magnetic field have been developed and employed for precisely targeted in vitro cell transportation over the past decades. However, manipulation of cells in vitro may not reflect the complexity of the situation inside multicellular organisms. A magnetic microrobot for manipulating a group of cells and enabling targeted cell delivery under in vivo conditions has not yet been developed. In this thesis, we introduce a biocompatible magnetic microrobot with porous spherical structure that functions as a microscaffold and microcarrier for in vivo studies. This research was conducted based on the following three aspects:First, a burr-like porous spherical magnetic microrobot for carrying biological cells was fabricated based on 3D laser lithography. The microrobot was coated with nickel (Ni) for magnetic actuation and titanium (Ti) for biocompatibility using a sputtering equipment. Viability tests performed on fibroblast MC3T3-E1 cells line and mesenchymal stem cells (MSCs) showed that the cells can readily adhere and proliferate over the structure of the robot; hence the designed robot is not cytotoxic to cells. Mechanical tests showed that the microrobot coated with Ni and Ti has a modulus of 33 MPa, which is large enough to support the cells as a transporter and also adequate to enable functionality in seeded cells. Cell loading experiments showed that the proposed burr-like microrobot structure improved loading capacity.
Second, the developed cell-cultured microrobot can be controlled to reach desired positions in vitro and in vivo using a home-made electromagnetic manipulation system. In vitro transportation experiments showed that the MC3T3-E1 cells-cultured microrobot can reach the targeted position along a desired triangular path successfully by changing the induced current loaded to each electromagnetic coil. In vivo experiments were further performed to transport the MSCs-cultured microrobot in the transparent yolk of zebrafish embryos, which allowed us to visualize and monitor the in vivo movement of the microrobot online.
Third, a cell release experiment (from the microrobot to the surrounding environment) was demonstrated in vitro and in vivo. After the microrobot carrying cells arrived at the desired site, the cells can be released spontaneously to the surrounding tissues, with the design of the microrobot structure. In vitro experiments that involved releasing cells from the microrobot onto a substrate were performed first, followed by in vivo tests and histological studies on nude mice. Results verified that the cells carried by the microrobot can be transferred onto a desired site successfully.
In summary, this study has demonstrated that the developed magnetic microrobot based on 3D laser lithography can be well utilized to carry functional cells to a desired site and release them spontaneously in vivo. This thesis represents a significant progress for the development of targeted cell-cultured microrobots that can be navigated precisely. The success of this study will constitute a technological platform for cell-based therapy and tissue regeneration for precise medicine in the future.
| Date of Award | 13 Dec 2017 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Dong SUN (Supervisor) |