Effects of UC-MSC–Derived EVs Encapsulated in DGEA-Decorated PA Hydrogels on Osteogenesis and Immune Modulation in a 3D Autocrine Culture Model

2nd Extracellular Vesicles Conference (TURSEV-26), Ankara, Türkiye, 5 - 06 Haziran 2026, ss.99, (Özet Bildiri)

Bone regeneration requires biomaterials that not only provide osteoinductive signals but also modulate inflammatory responses. In this study,

we investigated DGEA-decorated peptide amphiphile (PA) hydrogels, composed of DGEA-PA and K-PA, as three-dimensional microniches

for localized extracellular vesicle (EV) delivery and autocrine culture. To recapitulate a cell-secretome driven microenvironment, UC-MSCs

were seeded into hydrogels with or without UC-MSC-derived EVs, enabling a 3D autocrine culture system based on both cellular and

vesicular components from the same origin. Biocompatibility and cell adhesion were evaluated using MTT and Calcein AM staining at 24, 48,

and 72 h. Osteogenic potential was assessed by qPCR analysis of RUNX2, OCN, and OPN expression, as well as by Alizarin Red S staining

for mineralization. In addition, matrix remodeling and immune responses were examined through qPCR analysis of MMP2, MMP9, and

PLAU. MTT analysis confirmed that DGEA-decorated PA hydrogels maintained high UC-MSC viability over time, indicating good

cytocompatibility. Moreover, these hydrogels significantly enhanced cell adhesion, supported osteogenic marker expression, and promoted

mineral deposition. However, under the experimental conditions used in this study, UC-MSC-derived EVs did not further enhance osteogenic

differentiation or mineralization, suggesting that the regenerative efficacy of EVs is strongly influenced by their cellular origin and functional

cargo. Collectively, these findings demonstrate that DGEA-decorated PA hydrogels provide an osteoinductive 3D microenvironment and

underscore the importance of EV source selection in bone tissue engineering applications.