BioE Seminar Series: Engineering Sex-Aware and Biomimetic Platforms to Investigate Macrophage Function, Fibroblast Remodeling, and Monocyte Infiltration

Engineering Sex-Aware and Biomimetic Platforms to Investigate Macrophage Function, Fibroblast Remodeling, and Monocyte Infiltration
Sex differences, immune dysfunction, and tissue remodeling are critical drivers of women’s health disorders, yet their combined contributions remain poorly understood. Our work integrates three complementary studies to uncover immune-stromal interactions across contexts of hormonal regulation, fibrosis, and autoimmunity.
Sex-specific macrophage responses: Using male-derived (RAW 264.7) and female-derived (J774A.1) murine macrophage cell lines, we investigated the effects of 17β‑estradiol (E2) on estrogen receptor signaling, phagocytosis, and inflammatory phenotypes. RAW 264.7 macrophages exhibited increased ESR1 expression and enhanced phagocytic capacity at high E2 doses, whereas J774A.1 macrophages showed reduced ESR1 expression and impaired phagocytosis, revealing divergent estrogen sensitivities with implications for immune regulation.
Uterine fibroid remodeling: We developed a biomimetic PEG-based hydrogel platform to model fibroblast-driven extracellular matrix (ECM) remodeling in uterine fibroids. Primary human uterine fibroblasts treated with TGF‑β3 exhibited stiffness-dependent activation, characterized by increased α‑smooth muscle actin, collagen deposition, and fibroblast elongation in fibroid-like environments. This platform enables mechanistic studies of ECM-driven fibrosis and offers a physiologically relevant model of fibroid pathogenesis.
Autoimmune monocyte infiltration: To investigate immune recruitment under inflammatory conditions, we engineered a novel PDMS-PEG microfluidic platform mimicking vascular-tissue interfaces. Upon lipopolysaccharide (LPS) stimulation, monocytes exhibited significant migration from a central microchannel into a surrounding 3D hydrogel matrix, demonstrating the system’s ability to model immune infiltration dynamics.
Together, these studies provide complementary insights into hormonal, mechanical, and inflammatory regulation of immune-stromal interactions, advancing physiologically relevant platforms for women’s health and autoimmune disease research.