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    The development of a steerable needle robot with biomaterials for the application of 3D printing in situ towards in vivo artificial muscles : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Engineering at Massey University, Palmerston North, New Zealand
    (Massey University, 2023) Odendaal, Jean Henri
    Additive manufacturing is an emerging and continually growing field of research with great potential in the development of new technologies through which to change the world as we know it. This thesis offers a look from a 3D printing perspective towards the diverse fields of artificial muscle fabrication, bioprinting, polymer chemistry which can effect shape change or other responses under stimuli, as well an in detail investigation into steerable needle robotics and its potential as a mechanism for additive manufacturing. Since the 3D printing of (bio)polymers is generally reserved for the fabrication of structures on beds which are far away from where their intended use is intended, this thesis proposes an approach to 3D printing exactly the polymer that is of interest in the location in which it is intended. This thesis presents the research and development of a flexible steerable needle robot for the application of 3D printing (bio)polymers which could take the form of artificial muscles, bone, nerves, etc. in vivo. This is extremely challenging, however, and the research undertaken is intended towards building the capability to one day in future achieving this goal. Several experiments are presented which explore the characteristics of a custom developed steerable needle robot in application for 3D printing which include: its mechanisms, its control systems, its algorithms to accurately reach a target goal within a presented body, as well as it visualization system. Furthermore, this developed robot is then utilized to ”3D print” a (bio)polymer inside of a prepared phantom body (e.g., gelatine) to fabricate a bio-fiber. While the bio-fibers presented by this thesis are simple and do not react under any stimulus to act as an artificial muscle, there is a further future opportunity identified which could utilize advanced polymer chemistry to in fact achieve this end result. This thesis contributes towards the synthesis of multiple fields of research towards the goal of one day realizing the imagination of science fiction. Namely, the ability to quickly regenerate human tissue without the need for complex surgeries as well as the fabrication of fibers which could form part of artificial limbs or bodies.
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    Design and engineering of self-assembling antigens towards particulate vaccines : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Microbiology at Massey University, Palmerston North, New Zealand
    (Massey University, 2019) Chen, Shuxiong
    Natural and synthetic self-assembling polymers and proteins could be bioengineered to display and/or encapsulate antigens to serve as innovative antigen carrier systems for the induction of desirable immunities. Polyhydroxyalkanoates (PHAs) are naturally occurring polyesters synthesized as cytoplasmic polyester inclusions (polyester particles) by various bacteria. The particles have been used as an antigen delivery platform by translationally fusing antigens to the particle surface-associated protein, PHA synthase. Furthermore, it has been found that protein inclusion bodies contain a large amount of correctly folded and biologically active proteins and could be engineered to perform as an antigen carrier system. Tuberculosis (TB) is a global health issue for both humans and animals. Inaccurate diagnosis and inefficacious vaccination make TB control problematic. The Mantoux tuberculin skin test gives false positive results if humans or animals are vaccinated with the Bacille Calmette-Guérin (BCG) strain or exposed to environmental mycobacteria. BCG cannot provide effective protection against TB. Subunit vaccines have great promise to protect against infectious diseases, but they are often weak immunogenically. A strategy to circumvent this problem is the use of self-assembly particulate vaccines, which could present multiple copies of antigens and serve as a depot for prolonged multivalent antigen display to induce enhanced immunogenicity. In this thesis, four specific TB diagnostic antigens — CFP10, Rv3615c, ESAT6, and Rv3020c — were displayed on polyester particles. The results showed that polyester particles displaying TB antigens specifically distinguished TB-infected from non-infected cattle. Antigen immunogenicity was dramatically enhanced after the display on polyester particles, which lowered the antigen concentration (0.1 to 3 μg dose/inoculum) required for skin tests. Mycobacterial vaccines H4 (Ag85B-TB10.4) or H28 (Ag85B-TB10.4-Rv2660c) were bioengineered to display H4/H28 on polyester particles and/or self-assemble H4/H28 into protein inclusion bodies. The results demonstrated that polyester particle-/protein inclusion body-based particulate TB vaccines increased overall immunogenicity by enhancing humoral (for example, IgG1 and IgG2c) and cellular (for example, IFNγ and IL17A) immune responses when compared to respective soluble antigens.