| dc.description.abstract | Engineered living materials (ELMs) that integrate living cells and synthetic materials have been created with stimuli-responsive capabilities. ELMs can harness the biological functions of cells and detect subtle changes in the environment, which enable them to respond in a programmed manner. Importantly, genetic engineering the living component enables the fabrication of ELMs with engineered responses to a wide range of stimuli. ELMs comprised of genetically engineered microorganisms can be programmed to perform desired functions, such as shape-morphing and drug delivery, and thrive in a wide range of environmental conditions. ELMs can be formed using probiotics, providing a multimodal mechanism of action in biomedical devices. This dissertation focuses on a series of studies carried out to understand the fundamental critical tools needed to fabricate ELMs with programmed responses primarily derived from the biological activity of microorganisms. These responses are studied to understand the mechanical changes of the embedding matrix and the chemical changes surrounding ELMs for their potential use in biomedicine.
In the first study, baker’s yeast was embedded in acrylic hydrogels to form responsive ELMs capable of mechanical transformation by controlling cell proliferation. Yeast was capable of proliferating within the soft hydrogel matrix, leading to a controllable global expansion of the composite. Genetic engineering of the yeast enabled ELMs that changed in volume in response to specific amino acids and blue light.
In the second study, ELMs with yeast probiotics, acrylic hydrogels, and cellulose nanocrystals were fabricated using direct-ink-write printing. Printed ELMs containing genetically engineered probiotics changed shape into complex structures. Reservoir-based drug delivery capsules were fabricated for on-demand delivery of model drugs in response to specific biomolecules.
Lastly, prokaryotic ELMs were studied to understand long-term bacterial cell release to the surroundings. Materials were prepared with different stiffnesses and concentrations of cells to control cell release from the ELM. In future applications, ELMs made with prokaryotic probiotics can be used in in vitro studies to inhibit the growth of uropathogenic strains related to urinary tract infections.
Overall, future advances of ELMs with programmed functions, where microorganisms are programmed to respond to disease-specific stimuli, will offer new applications in drug delivery. | |
