Collagen Hydrogel Loaded With Propolis‐Loaded ZIF‐8 Nanoparticles and Menstrual Blood Stem Cells for Osteoarthritis Treatment

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage breakdown and chronic inflammation. Current therapies mainly relieve symptoms but do not halt disease progression. We developed collagen hydrogels incorporating propolis-loaded zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (PROZIF) and menstrual blood-derived stem cells (MenSCs). In vitro assays evaluated microstructure, cell viability, anti-inflammatory activity, drug release, and cytoprotection. An osteoarthritis model was induced in rats by monosodium iodoacetate (MIA). Animals received intra-articular injections of hydrogels, and outcomes were assessed by histology, enzyme-linked immunosorbent assay (ELISA), knee swelling, and locomotor function. Collagen-PROZIF-MenSCs hydrogels with 2% nanoparticle content (COL-PROZIF-MenSCs-2) preserved MenSC viability, showed strong anti-inflammatory effects, and provided sustained propolis release. In vivo, this group significantly reduced cartilage degeneration, decreased tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β), and increased transforming growth factor-beta (TGF-β) and fibroblast growth factor (FGF) levels compared to controls. Knee swelling was reduced, and locomotor scores improved. Combining ZIF-8 nanoparticles with MenSCs in collagen hydrogels synergistically mitigated OA progression in rats by reducing inflammation and supporting cartilage repair. This approach demonstrates promise as a localized, cell- and drug-based therapy for OA, warranting further long-term and translational studies.