Synthesis and Characterization of Collagen-Mimicking Hydrogels to Examine Lung Fibrosis

Dummeldinger, Michael
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University of Delaware
Idiopathic pulmonary fibrosis (IPF) presents a challenge even in this age of advanced medical technology. The causes and progression of the disease in humans remain largely unknown as it is often diagnosed well after it has begun and is difficult to observe in vivo. This thesis presents work towards the development of a new model for the collagenous extra-cellular matrix (ECM) found in the interstitial space of the human lung to aid in the research of the cellular responses that contribute progression of IPF. First, collagen mimetic peptides that assemble into triple helices were synthesized for the incorporation into hydrogels. Challenges arose in the synthesis of initial peptides compositions of K(aloc)G(POG)7GK(aloc), which included additional amino acid residues that contain orthogonal reactive groups. Consequently, subsequent testing focused on determining the best method to synthesize this new class of peptides, including synthesizing the sequences (POG)4, (POG)7, and K(alloc)(POG)7 on different resins. Second, hydrogels were synthesized and characterized on a rheometer to determine the compositions with similar physical properties to those of healthy and diseased human lung tissue, from 10 to 20 kPa. Poly(ethylene glycol) compositions of 10% and 12.5% weight percent were identified to mimic these moduli, respectively, and these syntheses demonstrated the high level of control that can be exercised on the final properties of the hydrogel based on the concentration of reactants. Future directions for this work will include attempting new peptide sequences that do not include K(alloc) and incorporating these new peptides into hydrogels that will be used to obtain the cellular responses to their physical environment.