Date of Award
Chemistry and Biochemistry
Acute inflammation is a natural biological defensive response against infection,irritation, and injury. While inflammation is a natural process, chronic tissue inflammation has been implicated in the development of several different diseases. With the intent of minimizing collateral damage associated with long-term exposure of healthy tissues to anti-inflammatory drugs, the Pedigo laboratory has designed a system for the self-assembly of protein polymers as scaffolds for controlled-release of drugs to affected tissues. This protein polymer comprises two essential components, with the first component being the calcium-dependent protein, calmodulin, and the second being a corresponding binding peptide, M13. Because Calmodulin has a specific, high affinity for the M13 peptide, and because the human body has an inherently high concentration of extracellular calcium, we expect that the two polymers will interact in a calcium- dependent manner forming a supramolecular polymeric matrix. This protein-based matrix will be covalently modified with anti-inflamatory agents like asprin or ibuprofen. Assembling this system at the site of chronic inflammation will allow for the controlled in situ delivery of medication, which would in turn significantly reduce dosage and eliminate the adverse effects accompanying systemic delivery of medications. An essential component of this nascent research is determining the toxicity of the protein scaffold. Through collaboration with Dr. Shabana Khan in the Natural Products Center, made possible by funding from the Sally McDonnell Barksdale Honors College, access to state of the art cell toxicity assays and several different cell lines has been made available for testing. The objective of this thesis is to perform cytotoxicity tests to demonstrate the viability of human cell lines when co-cultured with the self-assembling peptides, peptide derivatives, and peptide-polymer conjugates that compose the self-assembling biomaterial. This research is the first step for the foundation of further investigation into the in vivo safety of the biomaterials under development.
Vaughan, Peyton, "Cytotoxicity Assay of Self-Assembling Protein-Based Biomaterials" (2017). Honors Theses. 758.