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Structural Characterization & Introduction of Biomimetic Proteoglycans in Painful TMJ

Tuesday, June 11, 2019

1:00 PM-3:00 PM

BIOMED Master's Thesis Defense

Structural Characterization and Introduction of Biomimetic Proteoglycans in Painful Temporomandibular Joint (TMJ) Model

Melissa E. Franklin, Master's Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Michele Marcolongo, PhD
Department Head and Professor
Department of Materials Science and Engineering
College of Engineering
Drexel University

Beth Winkelstein, PhD
Eduardo D. Glandt President's Distinguished Professor
Department of Bioengineering
School of Engineering and Applied Science
University of Pennsylvania

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

Temporomandibular Joint disorders (TMJD) are the second-most common source of orofacial pain with 33% of adults having at least one TMJ disorder symptom. A significant subset of patients with TMJD develop osteoarthritis (OA), a progressive pathology characterized by intraarticular inflammation and fibrocartilage degeneration. Specific indications of osteoarthritic development are reorganization of collagen and loss of proteoglycans such as aggrecan. Loss of proteoglycans cause a decrease in tissue hydration, joint lubrication, and compromised compressive mechanics. Recent research suggests these structural changes are identifiable early within the pericellular matrix of the tissue.                   

The goal of this thesis was to evaluate the use of a novel biomimetic proteoglycan (BPG) as a treatment during early stages of TMJ osteoarthritis. BPGs have similar composition and properties to naturally occurring proteoglycans, but resist enzymatic degradation associated with hostile, osteoarthritic tissue environments. We initially established there is pericellular reorganization of collagen VI and aggrecan in joint overloading rat models of tunable TMJ pain, with more robust structural outcomes in joints exposed to 3.5N, resembling chronic pain, versus those exposed to 2N, representing acute pain. This established motivation to introduce BPG to this animal model. With ex-vivo diffusion of the biomimetic into TMJs from the acute and chronic pain models, we characterized BPG distribution and localization within the tissue matrix and found modulation between non-loaded, 2N, and 3.5N loaded TMJs.

Further, we identified a functional role of BPGs to influence matrix mechanics of TMJ fibrocartilage. Together, these findings bridge the inflammatory and catabolic cascades of TMJ pain to tissue structural outcomes and provide a first look into the use of biomimetic proteoglycans as a way restore proteoglycans lost during early TMJ osteoarthritis known to induce associated symptomatic pain.

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