Development of innovative therapeutic strategies for osteoarthritis: exploring thermosensitive hydrogels, hiPSC-derived cells and cell-products, and novel drugs in preclinical models

Sayedipour, S.S. (2026)

Doctoral Thesis

This thesis focuses on developing innovative therapeutic strategies for osteoarthritis (OA), a prevalent and disabling joint disease for which no disease-modifying treatments currently exist. The central aim was to design and evaluate effective intra-articular interventions by combining advanced biomaterials with biological and pharmacological approaches.

An injectable, thermosensitive hydrogel was developed and optimized as a local delivery platform to enhance retention and efficacy of therapeutic agents within the joint. Using this system, three promising strategies were investigated in preclinical OA models. First, human induced pluripotent stem cell–derived mesenchymal stromal cells (hiMSCs) were evaluated as a reproducible and scalable alternative to traditional bone marrow–derived MSCs, demonstrating comparable therapeutic efficacy. Second, extracellular vesicles derived from hiMSCs (hiEVs) were explored as a cell-free therapy, offering similar regenerative and anti-inflammatory benefits while potentially improving safety and manufacturability. Third, the repurposing of iopanoic acid (IOP) was assessed, showing consistent disease-modifying effects in OA models.

Overall, the findings highlight that combining a biomaterial-based delivery system with advanced biological or pharmacological therapies enhances therapeutic outcomes. This work contributes to the development of clinically translatable, disease-modifying treatments for osteoarthritis and supports the advancement of next generation regenerative strategies.

• Osteoarthritis
• HiPSC-derived cells
• Extracellular vesicles
• Thermosensitibe hydrogel
• Biomaterials
• Destabilazation of the medial meniscus
• Osteochondral explants

• All authors: Sayedipour, S.S.
• Supervisor: Meulenbelt, I.; Weerd, L. van der
• Co-supervisor: Ramos, Y.F.M.
• Committee: Appelman-Dijkstra, N.M.; Bloem, J.L.; Leijten, J.C.H.; Kieltyka, R.E.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2026-05-07
• ISBN (print): 9789465342740