Development of a Platform Technology To Impart Immunomodulatory Activity to Complex Biomaterials

Thursday, May 30, 2024

12:30 PM-2:30 PM

BIOMED PhD Thesis Defense

Title:
Development of a Platform Technology To Impart Immunomodulatory Activity to Complex Biomaterials

Speaker:
Victoria Nash, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisor:
Kara Spiller, PhD
URBN Professor of Biomedical Innovation
School of Biomedical Engineering, Science and Health Systems
Drexel University

Details:
Tissue regeneration is a complex series of events, driven by highly plastic immune cells: macrophages. Typically, “pro-inflammatory” macrophages act early to support angiogenesis, while later acting “pro-reparative” macrophages support newly sprouted vasculature, assisting in tissue repair. Approaches used in biomaterials engineering to temporally influence macrophage phenotype are surface coating or encapsulation of cytokines, however these are not amenable to a variety of biomaterials. Affinity interactions, such as heparin or albumin have been leveraged for drug delivery and rely on weak interactions, like hydrogen bonding, to retain and deliver the drug. However, these systems require specific biomaterial formulations for drug delivery. While these systems work for small molecules and some amino acids, they are limited for cytokine delivery because weak interactions are not stable enough for effective delivery.

Biotin-avidin affinity becomes a favorable option because biotin, avidin (or its variants), can be directly conjugated to proteins, biomaterials, and even cells, without altering its bioactivity. Historically, avidin was first used as a model adjuvant, then explored as a protein carrier for adjuvants in vaccines, but modern uses of the affinity pair, biotin-avidin, range from analytical assays to targeted radioimmunotherapy. Biotin-avidin interactions are rarely used for drug release due to biotin’s low dissociation rate from avidin. However, release can be triggered by introducing free biotin to the system, promoting the release of biotinylated molecules from avidin. Yet it is not known how bioconjugation parameters can lead to spontaneous release between biotin and avidin. Or even how biotin or avidin influence macrophage phenotype. Therefore, the goal of this thesis is to determine how bioconjugation parameters can control biotin-avidin interactions to release an immunomodulatory cytokine from a model biomaterial to influence macrophage phenotype.

Contact Information

Natalia Broz
njb33@drexel.edu