1 option
Biophysical regulation of synovial fibroblasts and macrophages in osteoarthritis Sung Yeon Kim
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Kim, Sung Yeon, author.
- Language:
- English
- Subjects (All):
- Biomedical engineering.
- Physiology.
- Biochemistry.
- Biomechanics.
- Biophysics.
- 0541.
- 0786.
- 0487.
- 0648.
- 0719.
- Local Subjects:
- Biomedical engineering.
- Physiology.
- Biochemistry.
- Biomechanics.
- Biophysics.
- 0541.
- 0786.
- 0487.
- 0648.
- 0719.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (194 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Osteoarthritis (OA) is the most prevalent joint disease worldwide and a leading cause of chronic pain and disability, yet no disease-modifying treatment exists. Long regarded as a condition of mechanical wear-and-tear driven by cartilage breakdown, OA is now understood to be a whole-joint disease in which chronic inflammation and progressive tissue remodeling of the synovial membrane play critical and active roles. The synovium, the tissue lining the joint cavity, harbors a dynamic community of fibroblasts and macrophages whose dysfunction drives synovial inflammation, fibrosis, and impaired joint lubrication. Despite growing recognition of its importance, synovial fibrosis remains one of the least understood and most therapeutically neglected features of OA.This thesis investigates how the evolving biophysical environment of the osteoarthritic synovium, progressively stiffened by fibrotic matrix remodeling, modulates the behavior of resident fibroblasts and macrophages, and reprograms the crosstalk between these populations, to perpetuate chronic inflammation and fibrosis. To address this question, methodological, biomechanical, transcriptomic, and therapeutic approaches were integrated across a series of complementary studies. A standardized framework for histopathological evaluation of synovial pathology was first developed and validated in preclinical OA models, and tissue-scale mechanical properties of the synovial membrane were quantitatively characterized across disease progression. Single-cell transcriptomics then revealed that while surgical joint injury triggers a broad stromal and immune response, it is the failure of this response to resolve that defines the dichotomy between persistent fibrosis and successful tissue repair. A preclinical therapeutic evaluation of mechanotransductive pathway inhibition further demonstrated that translating mechanotherapy to the synovial context presents unique challenges not anticipated by its efficacy in other fibrotic diseases.Collectively, this work establishes synovial matrix stiffening as a biologically consequential and quantifiable feature of OA, defines the cellular programs that sustain fibrotic remodeling, and identifies candidate targets for precision therapeutic intervention, advancing a mechanobiological framework for OA synovial fibrosis and laying the groundwork for synovium-targeted strategies capable of modifying disease rather than merely managing its symptoms
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Mauck, Robert L.; Scanzello, Carla R. Committee members: Vinning, Kyle; Maerz, Tristan; Wells, Rebecca G.; Dyment, Nathaniel
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247979487
- Access Restriction:
- Restricted for use by site license
The Penn Libraries is committed to describing library materials using current, accurate, and responsible language. If you discover outdated or inaccurate language, please fill out this feedback form to report it and suggest alternative language.