Student(s): Juliana Magarelli
Project: Developing an Inflammation-Responsive Drug Delivery System for Osteoarthritis
Advisor(s): Tomas Gonzalez-Fernandez, Lesley Chow
Abstract
Osteoarthritis affects over 32.5 million US adults and is driven by chronic inflammation, which accelerates cartilage degradation and undermines regenerative therapies. Anti-inflammatory drugs are effective at reducing pain, but systemic and frequent dosing increases risks of side effects, such as subchondral bone damage and accelerated cartilage loss. Thus, there is a need for next-generation delivery platforms capable of responding to inflammatory cues to achieve controlled, localized drug release within the joint. This study aims to develop a biomaterials-based system where drug release is triggered by inflammation. In this project, we used cyanine3 (Cy3) fluorophore as a model drug to track release. Cy3 was coupled to an enzyme-sensitive peptide (KRVKRRLLMET) before attaching to poly(caprolactone) (PCL) to form a Cy3-conjugate. Inks containing unmodified PCL and Cy3-conjugate were solvent-cast 3D printed to create scaffolds presenting Cy3 and the enzyme-sensitive peptide. Scaffolds were also printed with inks containing Cy3-peptide that was not tethered to PCL to quantify release of free Cy3-peptide. Cy3-conjugate and Cy3-peptide scaffolds were incubated in collagenase or buffer to evaluate their enzyme-specific release profiles compared to passive diffusion. Successful peptide and conjugate synthesis was confirmed by mass spectrometry and 1H NMR. Cross sectional fluorescence images of Cy3-conjugate scaffolds showed increasing fluorescence with increasing Cy3-conjugate concentration. Cy3-conjugate scaffolds exhibited higher Cy3 release in collagenase compared to in buffer. These findings demonstrate that our scaffold platform enables protease-responsive release of therapeutic molecules in an enzyme-rich inflammatory environment.
About Juliana Magarelli
Major: Bioengineering
Juliana is a third-year bioengineering undergraduate student at Lehigh University with interests in biomaterials, drug delivery, and regenerative medicine. She has been a member of the TGF and Chow Labs through the Clare Boothe Luce Research Scholars program since spring 2025. Her research focuses on characterizing the release kinetics of conjugated fluorophores from 3D-printed peptide–polymer scaffolds seeded with human mesenchymal stromal cells (hMSCs) for applications in osteoarthritis treatment. In particular, she studies how the presence of cells and extracellular matrix influence drug release within the scaffold microenvironment. After graduation, Juliana plans to pursue a PhD in bioengineering. Outside of the lab, she is a Global Social Impact Fellow, where she develops accessible healthcare education tools for medical students in Sierra Leone. Through both her research and global health work, Juliana is driven by a commitment to advancing equitable, translational solutions at the intersection of engineering and medicine.