{"id":{"repo_id":"cornell","oai_identifier":"oai:ecommons.cornell.edu:1813/111814"},"canonical_url":"https://search.dev.ndltd.org/etd/cornell/oai:ecommons.cornell.edu:1813/111814","repository":{"repo_id":"cornell","name":"Cornell University","base_url":"https://ecommons.cornell.edu/server/oai/request"},"display":{"title":"T cell Immunomodulation in the Lymph Node for Inhibition of Load-Induced Osteoarthritis","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Wheeler, Tibra Anita"],"institution":"Cornell University","degree_name":"Ph. D., Biomedical Engineering","degree_level":"Doctor of Philosophy","degree_discipline":"Biomedical Engineering","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":["Singh, Ankur","Maher, Suzanne A."],"year":2022,"date_issued":"2022-05","date_published":"2022-05","updated_at":"2026-07-24T01:48:56Z","subjects":["hydrogels","immunoengineering","osteoarthritis","T cells"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7298/c956-9n28"],"render_values":[{"text":"https://doi.org/10.7298/c956-9n28","href":"https://doi.org/10.7298/c956-9n28","code":true}]},{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["ProQuest Submission ID: 13083","ProQuest Publication ID: 29169027"],"render_values":[{"text":"ProQuest Submission ID: 13083","href":null,"code":true},{"text":"ProQuest Publication ID: 29169027","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/1813/111814","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Singh, Ankur","Maher, Suzanne A."]},{"key":"dc:creator","label":"Author","values":["Wheeler, Tibra Anita"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2022-09-15T15:51:38Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2022-09-15T15:51:38Z"]},{"key":"dc:date.issued","label":"Date","values":["2022-05"]},{"key":"dc:type","label":"Dc Type","values":["dissertation or thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctor of Philosophy"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph. 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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."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["T cell Immunomodulation in the Lymph Node for Inhibition of Load-Induced Osteoarthritis"]}]}],"canonical_facts":{"dc:contributor.committeemember":["Singh, Ankur","Maher, Suzanne A."],"dc:creator":["Wheeler, Tibra Anita"],"dc:date.accessioned":["2022-09-15T15:51:38Z"],"dc:date.available":["2022-09-15T15:51:38Z"],"dc:date.issued":["2022-05"],"dc:description":["147 pages"],"dc:description.abstract":["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."],"dc:format.mimetype":["application/pdf"],"dc:identifier.doi":["https://doi.org/10.7298/c956-9n28"],"dc:identifier.other":["ProQuest Submission ID: 13083","ProQuest Publication ID: 29169027"],"dc:identifier.uri":["https://hdl.handle.net/1813/111814"],"dc:language.iso":["en"],"dc:subject":["hydrogels","immunoengineering","osteoarthritis","T cells"],"dc:title":["T cell Immunomodulation in the Lymph Node for Inhibition of Load-Induced Osteoarthritis"],"dc:type":["dissertation or thesis"],"thesis:degree_discipline":["Biomedical Engineering"],"thesis:degree_level":["Doctor of Philosophy"],"thesis:degree_name":["Ph. D., Biomedical Engineering"],"thesis:institution_name":["Cornell University"]},"updated_at":"2026-07-24T01:48:56Z"}