Nature provides fascinating examples of functional materials with hierarchical structures. Nano and microscale materials have been prepared by synthetic approaches via the self-assembly of discrete building blocks with the aim to mimic nature’s materials in complexity and size. The solution-state self-assembly of block copolymers (BCPs) with crystallizable core-forming blocks has enabled access to low curvature morphologies such as 1D and 2D micelles via a spontaneous nucleation method termed crystallization-driven self-assembly (CDSA). Via a seeded growth method known as living CDSA, 1D and 2D micelles of controlled dimensions and low dispersity can easily be prepared. However, due to the challenges associated with the synthesis of high aspect ratio nanoparticles and the low number of noncytotoxic polymers known to undergo CDSA, their use for biomedical applications has been limited. The aim of the work described in this thesis is to develop nanofibers of precise dimensions, with nontoxic materials, for potential biomedical applications such as drug delivery, tissue engineering and materials reinforcement. Chapter 1 describes how nature makes superb functional hierarchical materials that serve as inspiration for the development of synthetic methods for the preparation of nano and microstructures. The principles regarding the solution-state self-assembly of BCPs with amorphous or crystalline core-forming blocks are discussed. The preparation of length-controlled nanostructures, segmented micelles, and supermicelles via living CDSA and micelle self-assembly are presented. An introduction to nanoparticle drug delivery, materials reinforcement, and tissue engineering with emphasis on the development and advantages of high aspect ratio nanofibers is given. Finally, a brief perspective on the development of nanofiber-based therapeutics is provided. Chapter 2 discusses the preparation of coaxial-core core nanofibers from the self-assembly of triBCPs. The nanofiber structure is comprised of a crystalline inner core, an amorphous hydrophobic outer core, and a water-soluble corona-forming block. Encapsulation of a model hydrophobic molecule was achieved by the outer amorphous core. This represents the first example of water-soluble, length-controlled, and low length-dispersity (Ð) nanofibers loaded via non-covalent interactions. In Chapter 2, preliminary studies suggested cargo uptake by diBCP nanofibers may be possible. Chapter 3 focusses on investigating the non-covalent loading of length controlled diBCP nanofibers with a hydrophobic cargo. The effect of the chemical identity and the length of the corona-forming blocks was also studied. Chapter 4 describes the self-assembly of B-A-B triBCPs with crystallizable hydrophobic ‘B’ terminal segments to yield fiber-like micelle networks and their potential applications. Conditions for the preparation of discrete crystalline core flower-like micelles and intermicellar fiber-like networks of crystalline core nanofibers were investigated. For the first time, crystalline core nanofiber networks are reported. Chapter 5 focuses on the proof-of-concept development of water-soluble length-controlled nanofibers with corona-forming blocks capable of targeting specific cancer tissue. Additionally, segmented nanofibers for drug delivery applications were prepared. Finally, the association of curcumin with the nanofiber corona-forming block was briefly investigated. Chapter 6 summarizes the work presented in this thesis which contributes towards the development of length-tunable nanofibers for biomedical applications and outlines future research directions of the work presented. / Graduate / 2023-04-20

京都大学 / 0048 / 新制・課程博士 / 博士(エネルギー科学) / 甲第21190号 / エネ博第364号 / 新制||エネ||71(附属図書館) / 京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻 / (主査)教授 佐川 尚, 教授 森井 孝, 教授 松田 一成 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DGAM

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Yes / Physical properties of scaffolds such as nanofibers and aligned structures have been reported to exert profound effects on the growth and differentiation of stem cells due to their homing-effect features and contact guidance. However, the biological function of aligned nanofiber utilized as bone-scaffold has not been rigorously characterized. In the present study, aligned electrospun cellulose/CNCs nanocomposite nanofibers (ECCNNs) loaded with bone morphogenic protein-2 (BMP-2) were used for the first time to investigate (1) in vitro osteogenic differentiation of human mesenchymal stem cells (BMSCs) and (2) in vivo collagen assembly direction and cortical bone regeneration. Aligned ECCNNs scaffolds loaded with BMP-2 possess good biological compatibility. The growth orientation of BMSCs followed the underlying aligned nanofibers morphology, accompanied with increased alizarin red stain, ALP activity and calcium content in vitro while, a rabbit calvaria bone defect model was used in an in vivo study. / This work was supported by Natural Science Foundation of China (NSFC) grants (31500789, 51433006, 51473100, 81870758 and 31871464), Chongqing Yuzhong District science and technology plan project grants (20170124), Chongqing Research Program of Basic Research and Frontier Technology (cstc2018jcyjAX0807, cstc2017jcyjBX0019 and cstc2017jcyjAX0020), Temple University Kornberg School of Dentistry research start-up funds, the RCUK China-UK Science Bridges Program through the Medical Research Council and the Engineering and Physical Sciences Research Council and Program for Innovation Team 1015 Building at Institutions of Higher Education (No. 1016 CXTDG201602006) funded by the Chongqing Municipal 1017 Education Commission of China in 2016