(2ip) Engineering Biomaterials for Women's Health

Immunoengineering is a relatively new discipline that combines the use of engineering tools to research the immune system. Autoimmune diseases are a malfunction of the immune system, in which impaired immune education and stimulation leads to immune cells attacking critical host functions, generating life-threatening side effects. Most notably, these conditions disproportionately affect women at a 2 to 1 ratio [1]. Disparity in funding between female-specific disorders and male-specific disorders aggravates the lack of research in this field and thus, treatments for autoimmune diseases remain limited [2, 3]. My long-term goal is to launch a research program focused on improving therapeutic options for female-specific disorders, where my team will apply materials-based approaches to create models and therapeutics targeting autoimmune diseases to advance disease understanding and test new therapeutic modalities.

My training to date has been focused on building expertise needed towards this goal. My Ph.D. work focused on the use of nanomaterials to treat and target triple negative breast cancer (TNBC), a disease that mostly affects women. TNBC is a type of breast cancer that lacks the three common receptors used for immunotherapy and has a tendency to metastasize faster, leaving fewer treatment options. Platinum nanoparticles (Pt NPs) were investigated as a possible substitute for chemotherapeutic drugs, as they possess strong efficacy against TNCB-cells with limited toxicity to healthy cells [4]. To avoid off-target effects and improve NP bioavailability, Pt NPs were encapsulated in poly(lactic-co-glycolic acid) (PLGA) carriers. Surface modifications with polyethylene glycol (PEG) were performed to enhance circulation-time, as well as the conjugation with epidermal growth factor (EGF), which is overexpressed in TNBC. Based on the promising results achieved in vitro, PLGA-Pt NPs biodistribution was studied in vivo in healthy BALB Nude mice, discovering accumulation in the liver and spleen. This work established a critical foundation for use of PLGA-Pt NPs as a translational treatment for TNBC, while advancing my own expertise in NP administration and consideration of biological barriers when designing novel biomaterials.

As a postdoctoral researcher, I was interested in continuing to apply novel biomaterials towards medical applications and learn about applications to the immune system. At the University of Delaware, I am working to develop a novel device to produce CAR T cells that leverages hydrogel scaffolds and tangential flow filtration [5]. In this project, I have focused on the use of PEG hydrogels with different stimulatory molecules to activate T-cells, leading to distinct modulation of desirable phenotypes. The use of hydrogels emulates the in vivo microenvironment which allows for a rapid and more controlled activation with lower exhaustion, especially when compared to commercially available systems. This work presents significant opportunities to improve the existing manufacturing of CAR T cells. Moreover, this project has expanded my knowledge in cell therapy and provides expertise needed to address therapeutic challenges in autoimmunity.

Collectively, the combination of my Ph.D. and postdoctoral research has built my understanding of the use of biomaterials in the body and the different barriers that must be overcome in order to have therapeutic effect. By applying my expertise with T-cells modulation within the autoimmune environment and my background in NP therapeutics, I aim to engineer new models and therapeutic approaches to modulate autoimmunity and enable new translation options for women facing autoimmune diseases.

References:

1. Angum, F., et al., The Prevalence of Autoimmune Disorders in Women: A Narrative Review. Cureus, 2020.
2. Mirin, A.A., Gender Disparity in the Funding of Diseases by the U.S. National Institutes of Health. J Womens Health (Larchmt), 2021. 30(7): p. 956-963.
3. Swingle, K.L., et al., Delivery technologies for women’s health applications. Nature Reviews Bioengineering, 2023.
4. López Ruiz, A., E. Villaseco Arribas, and K. McEnnis, Poly(lactic-co-glycolic acid) encapsulated platinum nanoparticles for cancer treatment. Materials Advances, 2022. 3(6): p. 2858-2870.
5. Bomb, K., et al., Cell Therapy Biomanufacturing: Integrating Biomaterial and Flow‐Based Membrane Technologies for Production of Engineered T‐Cells. Advanced Materials Technologies, 2023: p. 2201155.