T cell Immunomodulation in the Lymph Node for Inhibition of Load-Induced Osteoarthritis

Other Titles


Osteoarthritis (OA) is a degenerative joint disease that affects millions of people worldwide. The molecular mechanisms of OA initiation and progression are poorly understood and currently, no disease-modifying treatments exist. Intra-articular injection of anti-inflammatory therapeutics is a common treatment option for OA but is limited by poor drug retention. While biomaterials-based strategies have been used to overcome the limitations of current OA treatments, there is a need for more targeted approaches. Understanding the immune response will enable the development of a rational immunotherapeutic approach targeting specific immune cells. However, the crosstalk of joint pathology with local lymph nodes in OA is poorly understood. We characterized the T cell immune response in local lymph nodes following the in vivo mechanical loading of joints. First, we analyzed the change in T cells in lymph nodes following load-induced OA using flow cytometry. T cells increased in the local lymph nodes and contributed to load-induced OA progression in the mouse knee. T helper and γδ T cells increased in the lymph nodes with prolonged cyclic tibial compression. Both pro- and anti-inflammatory cytokines increased with damaging joint loading. Next, we determined the role of T cell presence and migration in OA progression using TCRα-/- and Sphingosine-1-phosphate (S1P) receptor modulator-treated mice, respectively. Inhibiting T cell migration attenuated load-induced cartilage degradation and decreased localization of T cells in the synovium. Furthermore, the absence of  T cells, but not γδ+ T cells (TCRα-/- mice), reduced cartilage degradation and osteophyte formation. Lastly, we engineered and assessed the in vivo efficacy of an injectable, protease-degradable PEG-4MAL hydrogel combined with a commonly-used corticosteroid, dexamethasone (DEX). PEG-4MAL hydrogels maintained their mechanical properties after cyclic compression and released therapeutics in an on-demand manner in vitro. Furthermore, the PEG-4MAL hydrogel functioned as a mechanical pillow to protect the knee joint from symptoms of load-induced OA in vivo. These results lay the foundation for the role of T cells in joint damage and suggest that the lymph node may modulate the immune response in OA. Our findings indicate T cell immunotherapies in combination with the PEG-MAL hydrogel system could be used to treat OA.

Journal / Series

Volume & Issue


147 pages


Date Issued




hydrogels; immunoengineering; osteoarthritis; T cells


Effective Date

Expiration Date




Union Local


Number of Workers

Committee Chair

der Meulen, Marjolein van

Committee Co-Chair

Committee Member

Singh, Ankur
Maher, Suzanne A.

Degree Discipline

Biomedical Engineering

Degree Name

Ph. D., Biomedical Engineering

Degree Level

Doctor of Philosophy

Related Version

Related DOI

Related To

Related Part

Based on Related Item

Has Other Format(s)

Part of Related Item

Related To

Related Publication(s)

Link(s) to Related Publication(s)


Link(s) to Reference(s)

Previously Published As

Government Document




Other Identifiers


Rights URI


dissertation or thesis

Accessibility Feature

Accessibility Hazard

Accessibility Summary

Link(s) to Catalog Record