Date of Award

2018

Document Type

Open Access Dissertation

Department

Biomedical Science

First Advisor

Jay Potts

Abstract

Biodegradable alginate microcapsules (MC) are recently becoming widely used in the biomedical field, and have shown effectiveness as a drug delivery system. Alginate has been used in microencapsulation due to its simple gelling process, biodegradability, excellent biocompatibility, and its stability under in-vivo conditions. Alginate polymer is a natural polysaccharide derived from brown seaweed and has the ability to polymerize rapidly in the presence of cations to form a porous matrix. In order to advance the previous system for efficient protein and peptide delivery, we further lyophilized the peptide-filled microcapsules and we were able to rehydrate, and test them for sustained release. Electrospray method, as a microencapsulation technique, has been previously used to encapsulate peptides and proteins successfully using alginate. A second coating of poly-l-ornithine (PLO) polymer can be used to increase the integrity of alginate microcapsules. Alpha-carboxy terminus 1 (αCT1) peptide, Human platelet lysate (HPL), and bovine serum albumin (BSA) were examples of peptides and proteins that were successfully encapsulated by our lab. Cell-based therapies represent a revolutionary bio-technique that has been applied widely in medicine. Recently, they have been successfully applied in treatment of neurodegenerative diseases, eye diseases, cardiovascular disease, diabetes, liver disease and cancer. Suppression of the host immune system is considered the main challenge in such therapies. In order to avoid the side effects of immunosuppressive drugs, encapsulating cells into polymeric matrices is considered a promising strategy. Encapsulation systems utilize permeable materials that allow diffusion of nutrients, waste and therapeutic factors into and out of cells, while masking the cells from the host immune response. In our model, we have been encapsulating ARPE-19, human immortal cell line, that was genetically designed to express and secret CR2-fH protein to test them for safe and effective long term inhibition in vivo. CR2-fH is a complement inhibitor molecule that has been recently found to express promising therapeutic effects in both in vivo and in vitro models of Age-related Macular degeneration (AMD). Furthermore, human skeletal muscle differentiating cells (skMDC) that were recently used in biomedical research to investigate skeletal muscle behavior, function, and ability to be implemented in tissue regeneration field for further applications of disease advanced therapies. In this study we hypothesize that alginate encapsulation using high voltage method can be enhanced and advanced further to use it in different clinical approaches and applications. The present study shows the successful formation of alginate-poly-Lornithine microcapsules using the above-mentioned method, according to specific parameters, to produce microcapsules about 200 mm in diameter. The microcapsules derived from this encapsulation technique according to our hypothesis can be freeze dried without harming the shape of the microcapsules in which they retain the original shape after hydration. The main purpose of lyophilization is to increase the shelf-life storage of encapsulated biomaterials as well as preserve its activity to be used for treatment. Moreover, the technique has the ability to preserve the metabolic activity of genetically engineered ARPE-19 cells and skMDC cells resulting in effective and safe long-term drug delivery for treatment. In addition, hydrogel systems have been utilized in combination with the previous approaches, lyophilized microcapsules and encapsulated cells, for more improvements in regenerative medicine and targeted delivery therapy fields

Available for download on Monday, January 28, 2019

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