Date of Award
12-2025
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Bioengineering
Committee Chair/Advisor
Dr. Agneta Simionescu
Committee Member
Dr. Dan Simionescu
Committee Member
Dr. Brian Booth
Abstract
Mitral valve (MV) fibrosis is a progressive pathological condition characterized by leaflet thickening and stiffening, ultimately compromising valve function. This process is accelerated in diabetes, where chronic hyperglycemia elevates reactive oxygen species (ROS) and alters the mechanics of the extracellular matrix (ECM), collectively promoting the activation of valvular interstitial cells (VICs). Under healthy conditions, VICs maintain a quiescent, fibroblast-like phenotype responsible for sustaining ECM homeostasis. However, pathological biochemical cues or mechanical stress drive VICs toward a myofibroblast phenotype. While this transformation is essential for short-term repair, its persistence contributes to maladaptive MV remodeling and fibrosis. Diabetic stressors may be mitigated by antioxidants such as rutin, a plant-derived glycoflavonoid. Rutin’s mechanism of action in diabetic VIC activation remains poorly understood, in part because these conditions are challenging to study in vitro and in vivo.
This work sought to address these limitations by developing a hydrogel-based culture system that mimics key features of the MV environment. The project included two primary aims: (1) to engineer an ECM-derived hydrogel capable of supporting VIC viability, and (2) to establish a model for examining VIC responses to diabetic injury with a dynamic seeding strategy. The optimized hydrogel supported the proliferation and fibroblast-like morphology of VICs over two weeks. Dynamic seeding within decellularized scaffolds enabled cell adhesion throughout the construct; however, reduced viability at three days suggested that oxygen limitations required further optimization.
Overall, this system provides a foundational platform for future studies investigating therapeutic strategies to prevent or slow the progression of MV fibrosis.
Recommended Citation
Hahn, Samantha, "Diabetes-Induced Mitral Valve Degeneration: Tissue-Engineered Solutions and Antioxidant Therapy" (2025). All Theses. 4622.
https://open.clemson.edu/all_theses/4622