POLYMERIC CAPSULES AND PARTICLES FOR ENCAPSULATION AND SELECTIVE RELEASE OF BIOMACROMOLECULES

Ph.DDOCTOR OF PHILOSOPH

Advanced Materials in 3D/4D Printing Technology

Advances made in 3D printing have opened new avenues for innovation in dental, aerospace, soft robotics, thermal regulation, and flexible electronic devices [...

Topology-dependent pH-responsive actuation and shape memory programming for biomimetic 4D printing

Biomimetic actuators are critical components of bionics research and have found applications in the fields of biomedical devices, soft robotics, and smart biosensors. This paper reports the first study of nanoassembly topology-dependent actuation and shape memory programming in biomimetic 4D printing. Multi-responsive flower-like block copolymer nanoassemblies (vesicles) are utilized as photocurable printing materials for digital light processing (DLP) 4D printing. The flower-like nanoassemblies enhance thermal stability, attributed to their surface loop structures on the shell surfaces. Actuators prepared from these nanoassemblies display topology-dependent bending in response to pH and temperature-programmable shape memory properties. Biomimetic octopus-like soft actuators are programmed with multiple actuation patterns, large bending angles (≈500°), excellent weight-to-lift ratios (≈60), and moderate response time (≈5 min). Thus, nanoassembly topology-dependent and shape-programmable intelligent materials are successfully developed for biomimetic 4D printing.National Research Foundation (NRF)Submitted/Accepted versionThis work was supported by National Research Foundation (NRF) Investigatorship in Singapore (NRF-NRFI05-2019-0001)

Networking of block copolymer nanoassemblies via digital light processing four-dimensional printing for programmable actuation

Controls over stimuli-responsive functional materials and programmable shape deformations are key features in the four-dimensional (4D) printing of soft actuators. Instead of using random copolymers, homopolymers, or natural polymers, this paper reports the first use of amphiphilic, photocurable, and pH-responsive block copolymer (BCP) nanoassemblies in digital light processing (DLP) 4D printing to fabricate smart and programmable soft actuators. Programmable actuation was studied via a bottom-up approach: (1) designed synthesis of pH-responsive BCPs, (2) nanoassembly structures of BCPs, and (3) networking of nanoassemblies via the photocuring process in DLP. As a proof-of-concept, bilayered grippers, ring-shaped actuators, and octopus-like actuators were programmed to produce a range of bending angles and actuation patterns. pH-responsive BCP nanoassemblies were also combined with commercially available three-dimensional printing liquid resin (PlasClear) to produce stimulus-responsive printing ink that was successfully used for 4D printing applications. Thus, smart and programmable materials were developed for 4D printing applications.National Research Foundation (NRF)Submitted/Accepted versionThis work was supported by National Research Foundation (NRF) Investigatorship in Singapore (NRF-NRFI05-2019-0001)

Synthesis of vinyl iodide chain-end polymers via organocatalyzed chain-end transformation

In the presence of alkynes (CH≡C–R2), iodide chain-end polymers (Polymer–I) were successfully transformed to vinyl iodide chain-end polymers (Polymer–CH=CR2–I) in a single step via organocatalysis. This reaction is completely metal-free and easy to carry out without using special reagents or special conditions. The polymers encompassed polyacrylates and polymethacrylate, and additional functionalities (e.g., OH and CF3) was also incorporated into the R2 moiety. The obtained Polymer–CH=CR2–I further served as a useful precursor for copper-catalyzed cross-coupling reactions with various thiols (R3–SH) to yield vinyl sulfide chain-end polymers (Polymer–CH=CR2–SR3) with various R3 moieties. Interestingly, under selected conditions, this organocatalysis also offered block-like copolymers containing a conjugated oligo-alkyne segment and a non-conjugated polyacrylate segment. Exploiting the unique structure, the block-like copolymer was used as an efficient dispersant of carbon nanotubes.National Research Foundation (NRF)Accepted versionThis work was partly supported by National Research Foundation (NRF) Investigatorship in Singapore (NRF‐NRFI05‐ 2019‐0001)

Capsule-like safe genetic vectors — cell-penetrating core – shell particles selectively release functional small RNA and entrap its encoding DNA

The breakthrough of genetic therapy is set back by the lack of suitable genetic vector systems. We present the development of permeability-tunable, capsule-like, polymeric, micron-sized, core–shell particles for delivery of recombinant nucleic acids into target cells. These particles were demonstrated to effectively release rod-shaped small hairpin RNA and to selectively retain the RNA-encoding DNA template, which was designed to form a bulky tripartite structure. Thus, they can serve as delivery vectors preloaded with cargo RNA or alternatively as RNA-producing micro-bioreactors. The internalization of particles by human tissue culture cells inversely correlated with particle size and with the cell to particle ratio, although at a higher than stoichiometric excess of particles over cells, cell viability was impaired. Among primary human peripheral blood mononuclear cells, up to 50% of the monocytes displayed positive uptake of particles. Finally, these particles efficiently delivered siRNA into HEK293T cells triggering functional knockdown of the target gene lamin A/C. Particle-mediated knockdown was superior to that observed after conventional siRNA delivery via lipofection. Core–shell particles protect encapsulated nucleic acids from degradation and target cell genomes from direct contact with recombinant DNA, thus representing a promising delivery vector system that can be explored for genetic therapy and vaccination.MOE (Min. of Education, S’pore

3D/4D Printing of Polymers: Fused Deposition Modelling (FDM), Selective Laser Sintering (SLS), and Stereolithography (SLA)

Additive manufacturing (AM) or 3D printing is a digital manufacturing process and offers virtually limitless opportunities to develop structures/objects by tailoring material composition, processing conditions, and geometry technically at every point in an object. In this review, we present three different early adopted, however, widely used, polymer-based 3D printing processes; fused deposition modelling (FDM), selective laser sintering (SLS), and stereolithography (SLA) to create polymeric parts. The main aim of this review is to offer a comparative overview by correlating polymer material-process-properties for three different 3D printing techniques. Moreover, the advanced material-process requirements towards 4D printing via these print methods taking an example of magneto-active polymers is covered. Overall, this review highlights different aspects of these printing methods and serves as a guide to select a suitable print material and 3D print technique for the targeted polymeric material-based applications and also discusses the implementation practices towards 4D printing of polymer-based systems with a current state-of-the-art approach

Capsule-like Safe Genetic VectorsCell-Penetrating Core–Shell Particles Selectively Release Functional Small RNA and Entrap Its Encoding DNA

The breakthrough of genetic therapy is set back by the lack of suitable genetic vector systems. We present the development of permeability-tunable, capsule-like, polymeric, micron-sized, core–shell particles for delivery of recombinant nucleic acids into target cells. These particles were demonstrated to effectively release rod-shaped small hairpin RNA and to selectively retain the RNA-encoding DNA template, which was designed to form a bulky tripartite structure. Thus, they can serve as delivery vectors preloaded with cargo RNA or alternatively as RNA-producing micro-bioreactors. The internalization of particles by human tissue culture cells inversely correlated with particle size and with the cell to particle ratio, although at a higher than stoichiometric excess of particles over cells, cell viability was impaired. Among primary human peripheral blood mononuclear cells, up to 50% of the monocytes displayed positive uptake of particles. Finally, these particles efficiently delivered siRNA into HEK293T cells triggering functional knockdown of the target gene lamin A/C. Particle-mediated knockdown was superior to that observed after conventional siRNA delivery via lipofection. Core–shell particles protect encapsulated nucleic acids from degradation and target cell genomes from direct contact with recombinant DNA, thus representing a promising delivery vector system that can be explored for genetic therapy and vaccination

3D direct printing of silicone meniscus implant using a novel heat-cured extrusion-based printer

The first successful direct 3D printing, or additive manufacturing (AM), of heat-cured silicone meniscal implants, using biocompatible and bio-implantable silicone resins is reported. Silicone implants have conventionally been manufactured by indirect silicone casting and molding methods which are expensive and time-consuming. A novel custom-made heat-curing extrusion-based silicone 3D printer which is capable of directly 3D printing medical silicone implants is introduced. The rheological study of silicone resins and the optimization of critical process parameters are described in detail. The surface and cross-sectional morphologies of the printed silicone meniscus implant were also included. A time-lapsed simulation study of the heated silicone resin within the nozzle using computational fluid dynamics (CFD) was done and the results obtained closely resembled real time 3D printing. Solidworks one-convection model simulation, when compared to the on-off model, more closely correlated with the actual probed temperature. Finally, comparative mechanical study between 3D printed and heat-molded meniscus is conducted. The novel 3D printing process opens up the opportunities for rapid 3D printing of various customizable medical silicone implants and devices for patients and fills the current gap in the additive manufacturing industry.National Research Foundation (NRF)Published versionThis research is supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Medium-Sized Center Funding scheme and the NTU Start-Up Grant

3D printing of hydrogel composite systems: recent advances in technology for tissue engineering

Three-dimensional (3D) printing of hydrogels is now an attractive area of research due to its capability to fabricate intricate, complex and highly customizable scaffold structures that can support cell adhesion and promote cell infiltration for tissue engineering. However, pure hydrogels alone lack the necessary mechanical stability and are too easily degraded to be used as printing ink. To overcome this problem, significant progress has been made in the 3D printing of hydrogel composites with improved mechanical performance and biofunctionality. Herein, we provide a brief overview of existing hydrogel composite 3D printing techniques including laser based-3D printing, nozzle based-3D printing, and inkjet printer based-3D printing systems. Based on the type of additives, we will discuss four main hydrogel composite systems in this review: polymer- or hydrogel-hydrogel composites, particle-reinforced hydrogel composites, fiber-reinforced hydrogel composites, and anisotropic filler-reinforced hydrogel composites. Additionally, several emerging potential applications of hydrogel composites in the field of tissue engineering and their accompanying challenges are discussed in parallel.MOE (Min. of Education, S’pore)Published versio