Fabrication, Actuation and Functionalization of 3D Hydrogel-based Microstructures


Student thesis: Doctoral Thesis

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Award date29 Aug 2019


Since hydrogel materials have good biocompatibility, 3D hydrogel-based microstructures have tremendous progress and application prospects in tissue engineering, intelligent materials, biomedical fields and so on. With the development of macromolecule science, bottom-up fabrication approach and the practical applications, considerable efforts and studies have been devoted to on functionalized hydrogel-based microstructures. However, there are still significant challenges to build 3D hydrogel-based microstructures with excellent bionic performance. Inspired by the structure and functional characteristics of a biological organism and tissue, we developed a series of bionic 3D hydrogel-based microstructures with high adaptability to various environmental conditions. By designing the surface composition and morphology of coiled microfiber-based microstructures, they can endow with multilayer membrane and magnetic actuation properties and functions, as well as for drug delivery. The development and functionalization of 3D hydrogel-based microstructures paves an alternative way for bionic structures construction and has potential applications for biomedical applications. The main research issues and results are summarized as follows:

Firstly, calcium alginate (Ca-alginate) microfiber is a well-known hydrogel-based microstructure. However, it is still a challenge to fabricate 3D microfibers-based structures with complex and hierarchical morphologies. Co-axial flow-based glass capillary microfluidic system is introduced for the scalable generation of coiled Ca-alginate microfibers. With the function of consecutive spinning and spiraling of the capillary device, different types of Ca-alginate microfibers can be obtained from straight, coiled to densely packed coiled structures by precisely adjusting the flow rates. Moreover, thus, the length, diameter, and thread pitch of the coiled microfibers are highly controllable during the generation processes.

Secondly, the tubular-like 3D tissue scaffold is an essential architecture in biomedical engineering, but its construction remains a big challenge for existing techniques. We report a multilayer tubular microcapsule fabrication method based on polyelectrolyte complex technique. The fabricated densely packed coiled Ca-alginate microfibers were coated with multilayer membrane through layer-by-layer adsorption of alginate and chitosan. After that, the structure was expanded and transformed into a multilayer tubular microcapsule structure by liquefaction. The multilayer tubular microstructure exhibits advantages in mechanical property and selective semi-permeable performance compared with original Ca-alginate microfiber.

Thirdly, one of the major challenges in creating and applying untethered microrobot, is maintaining their functionality when traveling in the physiological fluidic environment. Microorganisms can move in complex media respond to the environment such as bacteria, algae, spermatozoids, and cilia, and so on. A promising alternative strategy was developed to fabricate magnetic microrobots which two kinds of Ca-alginate microfibers were surface modified with magnetic nanoparticles for the controllability actuation Afterwards, we design the six DOFs magnetic coil control system to actuated microbats for mimicking biological matter. Benefiting from different magnetic nanoparticle assembly strategies, the helical and cilia-like microrobots can be magnetic actuation under different locomotion manners.

Finally, the proposed 3D hydrogel-based microstructures in this dissertation are endowed with multiple-functionalization and have potential applications in the drug delivery field. The functionalization of microstructures is essential to enhance their biomedical performance for targeted drug therapy. The magnetic nanoparticles and polyelectrolyte membrane were successfully functionalized on the helical hydrogel-based microstructures. The functionalized helical microcapsule showed the abilities to be wirelessly steered under rotating magnetic field and controllable release the carried drug models response to ions in the environment.

These indicate that such kind 3D hydrogel coiled microfiber based microstructures are highly versatile for implement sensing, actuation, and control drug delivery, Thereby, this research opens new prospects for the development and applications of 3D hydrogel-based microstructure, which is expected to give a long-term impact on the biomedical areas, such as for in vitro/vivo targeted therapy, tissue engineering, and organ-on-a-chip research.

    Research areas

  • capillary microfluidics, hydrogel microfiber, microcapsule, microrobots, LbL assembly, magnetic control, functionalization, drug delivery