Hierarchical wrinkle pattern drives tenogenic differentiation from human mesenchymal stem cells

Stem cells possess the unique abilities to self-renew and differentiate into various cell types, making them invaluable in tissue engineering and regenerative medicine. This study explores the behavior of human bone marrow-derived mesenchymal stem cells (hMSCs) on poly(dimethylsiloxane) (PDMS) substrates with hierarchical wrinkle patterns. These bio-inspired patterns were created using the surface instability of gold-coated elastomer bilayers. The results indicate that the hierarchical wrinkles not only promote cell alignment but also up-regulate tenogenic differentiation markers without chemical induction. The cells exhibited increased expression of tenocyte markers (<i>Mkx</i>, and <i>Col1</i>) and decreased expression of osteoblast (<i>Alp</i>, and <i>Opn</i>) and chondrocyte (<i>Sox9</i>) markers. This bio-inspired substrate design, mimicking natural extracellular matrix structures, provides a promising approach for developing functional tissue constructs and advancing stem cell-based regenerative therapies. The study underscores the importance of substrate topography in directing stem cell fate, highlighting its potential in mechanobiological applications and tissue engineering.