2nd Extracellular Vesicles Conference (TURSEV-26), Ankara, Türkiye, 5 - 06 Haziran 2026, ss.41, (Özet Bildiri)
Mesenchymal stem cells(MSCs) are characterized by high regenerative capacity, potent immunomodulatory properties, and a fibroblast-like
morphology. Among MSC sources, umbilical cord-derived MSCs(UC-MSCs) are considered particularly advantageous due to their high
proliferative potential, low immunogenicity, and strong regenerative efficacy. Extracellular vesicles(EVs) derived from UC-MSCs have
emerged as key mediators of tissue repair, including cartilage regeneration, by transferring bioactive molecules that regulate cellular
communication and differentiation. As the biological significance of UC-MSC-derived EVs has become better understood, their therapeutic
potential in cartilage tissue lesions has gained increasing attention. Previous studies have demonstrated that N-cadherin biomimetic peptides
with high regenerative potential can effectively induce chondrogenic differentiation in UC-MSCs. HAVDI stands for Histidine-Alanine-
Valine-Aspartic acid-Isoleucine, a pentapeptide sequence derived from the first extracellular domain of N-cadherin. However, the downstream
paracrine effects of these biomimetic microenvironments particularly on the composition and function of secreted EVs-remain insufficiently
characterized. In particular, the role of EVs released under N-cadherin-mimetic environment in modulating chondrogenic differentiation has
not been fully elucidated. In this study, UC-MSC-derived EVs were characterized and effects on in vitro chondrogenic differentiation were
systematically investigated using N-cadherin-mimetic peptide nanofiber systems. EVs obtained from four different culture conditions;
conventional two-dimensional (2D) UC-MSC culture, three-dimensional (3D) spheroid culture, 3D HAVDI peptide hydrogel culture, and 3D
scrambled (SCRAM) peptide hydrogel culture-were comparatively analyzed. EVs were isolated from conditioned media and characterized in
terms of particle concentration, size distribution, surface marker expression, and zeta potential. EVs derived from each culture condition were
applied to UC-MSCs undergoing chondrogenic induction at a concentration of 1 × 107 particles per 80,000 cells. The gene expression levels of
key chondrogenic markers (ACAN,SOX9,COL1A1, and COL2A1) were analyzed on days 3 and 10, together with using Safranin O staining.
The results demonstrated that UC-MSC-derived small EVs significantly support chondrogenic differentiation, with EVs obtained from
HAVDI-based biomimetic hydrogels showing the most pronounced effects. Overall, these findings highlight the critical influence of the N-
cadherin biomimetic culture environment on the functional properties of UC-MSC-derived EVs. The results provide a strong foundation for
the development of peptide-based EV therapeutics for cartilage repair and osteochondral regeneration, particularly in age-related degenerative
conditions.