Roles of Collagen V as a Mediator of Fibroblast Immune Responses and Meniscal Matrix Templating

Monday, October 27, 2025

11:00 AM-1:00 PM

BIOMED PhD Research Proposal

Title: 
Roles of Collagen V as a Mediator of Fibroblast Immune Responses and Meniscal Matrix Templating

Speaker:
Neil Patel,  PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisor:
Lin Han, PhD
Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Details:
Rare inherited diseases affect an estimated 3.5–5.9% of the global population, with most being genetically acquired and presenting in childhood. Despite their impact, these disorders remain poorly characterized and underdiagnosed. Classical Ehlers–Danlos syndrome (cEDS) is a rare connective tissue disorder affecting ~1 in 20,000 individuals, characterized by hyperextensible skin, joint hypermobility, easy bruising, and impaired wound healing that leads to atrophic scarring.

During tissue repair, fibroblasts respond to mechanical and immunomodulatory cues, coordinating extracellular matrix (ECM) degradation and regeneration. Type I collagen forms the primary scaffold, while type V collagen, a minor fibrillar collagen, regulates collagen I fibrillogenesis, fibril diameter, and organization. In cEDS, mutations in COL5A1 or COL5A2 disrupt these processes, resulting in disorganized matrix assembly. These defects are further influenced by inflammatory and regenerative cytokines, contributing to impaired healing. Using AFM-based nanoindentation we observed increase mechanical properties of Col5a1+/- cell derived matrix under immune challenge. Utilizing bulk-RNA sequencing, we found that Col5a1+/- fibroblasts constitutively activate the TGF- signaling pathway, along with cell-ECM interactions, both of which are persistent under immune challenge.

cEDS patients are also predisposed to early-onset osteoarthritis (OA), though the molecular mechanisms are not fully understood. The meniscus, critical for load distribution and joint stability, relies on an organized fibrocartilaginous ECM. Loss of collagen V is predicted to compromise ECM integrity, altering mechanosensing and matrix remodeling. Our previous work showed that collagen V regulates meniscal cell mechanosensing via the pericellular matrix, highlighting its role as both a structural and regulatory ECM component. In this work, siRNA mediated knockdown of porcine meniscal cells showed cell derived matrices have decreased mechanical properties, with matrices being less aligned. Using our custom 3D ring culture system and single harmonic generation (SHG), we show that Col5a1 knockdown results in impaired matrix reorganization. Building on these findings, we are testing the impact of modulating exogenous collagen V on the matrix elaboration and cell-matrix mechanosensing in embryonic meniscus cells. Results are expected to provide a foundation for improving meniscus matrix repair by leveraging collagen V and its mechanisms.

Contact Information

Natalia Broz
njb33@drexel.edu