Thesis

Processing considerations of silk fibroin for nanomedicine and eco-sensing applications

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Awarding institution
  • University of Strathclyde
Date of award
  • 2024
Thesis identifier
  • T16913
Person Identifier (Local)
  • 201963406
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Silk has demonstrated utility across a range of biomedical applications as it can be processed into several different material formats, such as films and nanoparticles. The translation of silk nanoparticle production to industrial scales can be aided through insight into the property drifts incited by nanoprecipitation scale-up and the identification of critical process parameters to maintain throughout scaling. Therefore, the principle hypothesis of this thesis is that silk processing methods can have improved scalability, specifically the manufacture of silk nanoparticles which are suitable for anticancer nanomedicine applications. To validate this hypothesis, nanoprecipitation conditions for the manufacture of native silk nanoparticles are established using a simple semi-batch method at the lab scale that reduced special-cause variation and improved mixing efficiency (Matthew, S. A. L. et al., ACS Biomater. Sci. Eng. 2020, 6, 6748−6759) (Chapter 2). The stirring rate was an important parameter affecting nanoparticle size and yield, while the initial dropping height directly affected nanoparticle yield. Varying the nanoparticle standing time in the mother liquor between 0 and 24 h did not significantly affect nanoparticle physicochemical properties. Next, the impact of key process and formulation parameters on the flow and mixing properties of native silk nanoprecipitation, as well as the resulting nanoparticle performance characteristics, are assessed in semi-batch and microfluidic format (Matthew, S. A. L. et al., RSC Adv. 2022, 12, 7357−7373) (Chapter 3). At flow rates where the shear rate was below the critical shear rate for silk, increasing the concentration of silk in both bulk and micro-mixing processes resulted in particle populations of increased sphericity, lower size, and lower polydispersity index. At high flow rates, where the critical shear rate was exceeded, the increased supersaturation with increasing concentration was counteracted by increased rates of shear-induced assembly. Then, the reproducibility of silk nanoprecipitation on volumetric scale-up in low-shear, semi-batch systems is reported and the reproducibility of chip parallelization for volumetric scale-up in a high shear, staggered herringbone micromixer is estimated (Matthew, S. A. L. et al., Molecules 2022, 27, 2368) (Chapter 4). Silk precursor feeds processed in an unstirred semi-batch system displayed significant changes in the nanoparticle physicochemical and crystalline properties following a 12-fold increase in volumetric scale between 1.8 and 21.9 mL. Conversely, microfluidic manufacture showed high between-batch repeatability and between-chip reproducibility across four participants and microfluidic chips. Silk nanoparticle properties can be improved by heterogenous chemical modification of the surface. Silk nanomedicines can then be achieved using surface adsorption to load the preformed nanoparticles with antioxidants. Due to the impact of COVID-19 (SARS-CoV-2) our working practices were impacted, and a new project was devised. Semi-crystalline silk ecosensors were designed using scalable origami folding of silk films and manufacture optimized by investigating process parameters, including diazonium coupling chemistry and natural dye adsorption (Matthew, S. A. L. et al. ACS Appl. Bio Materials 2022, 5, 3658–3666) (Chapter 5). Iron oxide spiking resulted in semi-autonomous movement in the presence of a magnetic field and azo-modification increased the film electromagnetic field strength. The optimized native and azo-silk, iron oxide spiked films could be loaded with natural dyes which indicated pH by eye and digital image colorimetry. A practical application was demonstrated—a battery free origami silk boat—as a colorimetric sensor for waterborne pollutants which was reusable at least five times. Overall, this thesis established key process and formulation parameters of silk nanoprecipitation in semi-batch and microfluidic formats and introduces silk eco-sensors by merging heterogeneous chemical modification, surface adsorption of natural dyes, responsive actuation, and origami techniques (Chapter 6).
Advisor / supervisor
  • Seib, Philipp
  • Perrie, Yvonne
Resource Type
Note
  • This thesis was previously held under moratorium from 3rd May 2024 until 3rd May 2026.
DOI
Date Created
  • 2023

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