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- Shi, Liyang, 1991-
(author)
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Injectable Composite Hydrogels Based on Metal-Ligand Assembly for Biomedical Applications
- 2018
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Doctoral thesis (other academic/artistic)abstract
- This thesis presents new strategies to construct injectable hydrogels and their various biomedical applications, such as 3D printing, regenerative medicine and drug delivery. These hydrogels cross-linked by dynamic metal-ligand coordination bonds exhibit shear-thinning and self-healing properties, resulting in the unlimited time window for injection. Compared with non-dynamic networks based on chemically reactive liquid polymer precursors that forms covalent bond during and/or post-injection, our injectable hydrogels with dynamic cross-linkages can be injected from an already cross-linked hydrogel state. Hyaluronic acid (HA) has been selected as the polymer due to its high biocompatibility and biodegradability. HA has been modified by attaching the bisphosphonates (BP) functionality as ligands for chelation of the metal ions or metal salts to form coordination cross-linkages. In the first part of this thesis, I presented the different chemical approaches to synthesize BP-modified HA (HA-BP) derivatives as well as HA derivatives dually modified with BP and acrylamide (Am) groups (Am-HA-BP). The structures of HA-BP derivatives were confirmed by NMR characterizations, e.g. by the peak at 2.18 ppm for methylene protons adjacent to the bridging carbon of BP in 1H-NMR spectrum and phosphorus peak at 18.27 ppm in 31P-NMR spectrum, respectively. In the next part, the hydrogels were constructed by simple mixing of HA-BP or Am-HA-BP solution with Ca2+ ions (Paper I), Ag+ ions (Paper II), calcium phosphonate coated silk microfibers (CaP@mSF) (Paper III), and magnesium silicate (MgSiO3) nanoparticles (Paper IV). The presented hydrogels exhibited dynamic features determined by reversible nature of coordination networks formed between of BP moieties of HA-BP or Am-HA-BP and metal ions or metal salts on the surface of the inorganic particles. Dynamic properties were characterized by rheological strain sweep experiments and strain-alternating time sweep experiments. Additionally, reversible coordination hydrogels were demonstrated to be further covalently cross-linked by UV light to form a secondary cross-linkage, allowing an increase of the strength and modulus of the hydrogels. In the last part of this thesis, biomedical applications of these hydrogels were presented. Am-HA-BP•Ca2+ hydrogel was extruded, using home-made 3D printer, then fixed by UV irradiation to fabricate multi-layered 3D tube-like construct (Paper I). In full-thickness skin defects of rat model, HA-BP•Ag+ hydrogel accelerated the wound healing process and increased thickness of newly-regenerated epidermal layer (Paper II). In the rat cranial critical defect model, double cross-linked Am-HA-BP•CaP@mSF hydrogel induced new bone formation without addition of biological factors and cells (Paper III). The anti-cancer drug loaded hydrogel was also prepared by mixing of the drug loaded MgSiO3 nanoparticles with HA-BP solution. The released particles from the hydrogel were shown to be taken up by cancer cells to induce a toxic response (Paper IV).In summary, this thesis presents metal-ligand coordination chemical strategies to build injectable hydrogels with dynamic cross-linking resulting in time-independent injection behavior. These hydrogels open new possibilities for use in biomedical areas.
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| 2. |
- Wang, Di
(author)
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Wear And Corrosion Resistance Lignin Coating
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Coatings are widely applied in industry and life since they safeguard materials from wear and corrosion, particularly in harsh environments. However, the application of traditional coatings always faces two challenges: (1) many traditional coatings are fossil-based and may have additives that are not environmentally friendly, and (2) the effectiveness of these coatings diminishes over time due to wear and corrosion. The environmental impact of coatings, particularly those designed for anti-corrosion and anti-wear, is a significant issue. Sustainable alternatives to traditional approaches are desirable and essential to grapple with environmental degradation and climate change. In addition, current methods for coating wear monitoring present several limitations. The requirement of complex external equipment or additional coating preparation steps increases the economic cost and limits the practical applicability of these monitoring systems in remote or harsh environments where deploying sophisticated equipment may not be feasible.In order to meet these challenges, the need for real-time wear monitoring methods and the development of sustainable materials based coating for corrosion and wear resistance are thus pressing concerns in machine elements, material science, and engineering. This work aims to embed lignin additives in coatings, optimising the lignin coating to achieve long-term corrosion resistance with improved wear resistance. Meanwhile, this research aims to monitor the coating’s corrosion and wear condition using TENG devices. The research opens possibilities for establishing in-situ and real-time coating condition monitoring.This thesis used lignin as the sustainable additive to achieve the coating with corrosion and wear resistance. Physical mixing and chemical grafting were two lignin modification methods. The assessment of coatings’ barrier properties and nanoscale wear resistance was characterised by EIS and nano scratch. A novel in-situ coating wear monitoring method based on a solid-liquid triboelectric nanogenerator (TENG) was introduced for coatings’ condition monitoring. A machine learning model was built and trained to deconvolute the TENG signal to predict the coating’s condition. The mechanism of using TENG for coating wear, corrosion and defect conditions monitoring was studied.Chemically grafted lignin with 15 wt% lignin had an impedance that remained at 105 Ω∙cm2 after being immersed in 1 M NaCl solution for a week. After improved by adding PDMS and DOPA pretreatment, the coated steel maintained a high barrier property (impedance level of 109 Ω∙cm2) in 1 M NaCl for around 100 days, which is much longer than for a commercial gelcoat. The lignin coating showed sufficient wear resistance with a low friction coefficient. TENG showed a corresponding signal after wear, while the CNN model using TENG current signals attained 99% prediction accuracy on the test set for coating corrosion stage classification. The main results for this thesis show that chemically grafting lignin as an eco-friendly additive in coating enhanced the performance of wear and corrosion resistance, paving the way for more sustainable coating applications. This self-powered TENG sensor generates relevant signals according to the coating degradation stage. It also eliminates the need for external equipment, offering a more practical solution for real-world applications.
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| 3. |
- Zhang, Shi-Jin, 1957-
(author)
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Regulation of Intracellular Calcium in Brown Adipocytes
- 1999
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Doctoral thesis (other academic/artistic)abstract
- Intracellular Ca2+ is considered a primary regulator of cell function. In the present study, the control and the effects of intracellular Ca2+ in brown adipocytes have been investigated. Cytosolic Ca2+ levels ([Ca2+]i) are the resultant of the activity of Ca2+ transport systems. Results concerning Ca2+transport systems in the plasma membrane, endoplasmic reticulum and mitochondria are presented.[Ca2+]i, monitored with Fura-2/AM, is increased when brown adipocytes are stimulated with norepinephrine (NE). The NE effect is mediated via a1-adrenoceptors and involves both release from intracellular Ca2+ stores and influx of extracellular Ca2+. The NE-induced [Ca2+]i response could be desensitized by pretreatment with NE. The desensitization is also mediated by a1-receptors and intracellularly by increased [Ca2+]i and calmodulin but not by protein kinase C. The kinetics of the desensitization are similar to those of inhibition of protein synthesis or transcription and the desensitization is associated with a comparable decrease in the number of a1-receptors.Mitochondrial Ca2+ levels ([Ca2+]m) were monitored within brown adipocytes with mitochondrially targeted aequorin. [Ca2+]m was not a simple reflection of [Ca2+]i; rather, evidence is presented for the existence of a b-adrenergic, cAMP-mediated signal that augments the [Ca2+]m/[Ca2+]i ratio. This signal causes the mitochondria to sequester Ca2+ even in the absence of increased cytosolic levels. Inhibition of mitochondrial Ca2+ uptake augments the cytosolic responses. Mitochondria may thus play an important role even in cytosolic Ca2+homeostasis in brown adipocytes.Chronic treatment of brown adipocytes with NE resulted in marked alterations of cytosolic Ca2+ handling, but the mitochondria retained their ability to sequester Ca2+during adrenergic stimulation, i.e. under conditions when UCP1 should be active.The effects of an increase in [Ca2+]i involve activation of a cAMP phosphodiesterase, and the presence of this component explains the unusual kinetic characteristics of norepinephrine-induced cAMP accumulation. [Ca2+]i is also involved in the regulation of gene expression: increased [Ca2+]i interacts synergistically with cAMP in the control of c-fos expression which may be of significance for regulation of cell proliferation and differentiation.It was concluded that Ca2+ is a primary regulator of physiological functions in brown adipocytes. The Ca2+ transport systems in brown adipocytes are involved in the regulation of intracellular and intraorganellar Ca2+. Changes of the free cytosolic Ca2+ concentration by hormone stimulation induces the activation of many physiological processes.
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