Date of Award

5-2025

Degree Type

Honors College Thesis

Academic Program

Polymer Science and Engineering BS

Department

Polymers and High Performance Materials

First Advisor

Tristan Clemons, Ph.D.

Advisor Department

Polymers and High Performance Materials

Abstract

Severe burns and other dermatological injuries are frequently accompanied by a range of comorbidities and aesthetic challenges that patients must contend with. The complexity of burn care is exacerbated by the lack of a standardized surgical protocol, as treatment strategies are tailored to individual patient factors, including overall health status, wound size and location, as well as the expertise and resources available to the surgical team. Most commonly, deep dermal burns are treated through grafting, which effectively covers the injury site, but requires the creation of a second wound on the body of approximately the same size. This produces a second wound capable of incurring infection which is detrimental to healing patients, and assumes the patient has sufficient healthy skin to utilize. Peptide amphiphiles (PAs) are a class of biomaterials composed of a peptide head and a hydrocarbon tail that self-assemble into nanostructures driven by non-covalent interactions between amino acids, leading to fiber formation through the incorporation of amino acid residues that engage in strong intermolecular hydrogen bonding. Importantly, these PA nanofibers can be designed to contain amino acids that prompt assembly into scaffolds highly reminiscent of the extracellular matrix and are shear thinning, making them ideally suited for spray delivery in wound healing applications. Peptide amphiphiles can also be functionalized to contain bioactive epitopes that are displayed on the exterior of the fibers, which can support desired cell processes such as blood vessel formation. Furthermore, PAs can also ionically crosslink with divalent cations via chelation with terminal carboxylic acid groups in the PA nanofibers, to form gels and create a favorable material profile to act as a scaffold for cell proliferation and reconstruction. In this work, PA monomers were synthesized by solid-phase peptide synthesis, with the molecular weight and purity of the PAs determined using liquid chromatography-mass spectrometry (LC-MS). Supramolecular polymerization of the PAs was evaluated through a Nile Red assay of the PA monomers, Circular dichroism (CD) was used to examine the internal ordering of the PA molecules during assembly, transmission electron microscopy was utilized for analysis of the nanofiber morphology, scanning electron microscopy aided in confirming the self-assembly post-spray, and rheological assessments were performed on the gelled PAs to assess viscoelasticity of the biomaterials. Biocompatibility of the PAs was assessed using a lactate dehydrogenase assay in human embryonic kidney cells. Cell viability and migration through gelled PAs was analyzed using confocal microscopy. Lastly, the angiogenesis capabilities of the bioactive PA nanofibers were assessed via blood vessel formation using an endothelial cell tube formation assay. All of these properties together prove for a promising future in the use of PAs as an effective biomaterial for tissue reconstruction, with the potential to significantly advance wound healing therapies

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