Enhancing metabolic activity and differentiation potential in adipose mesenchymal stem cells via high-resolution surface-acoustic-wave contactless patterning.

Acoustofluidics has shown great potential for label-free bioparticle patterning with excellent biocompatibility. Acoustofluidic patterning enables the induction of cell-cell interactions, which play fundamental roles in organogenesis and tissue development. One of the current challenges in tissue engineering is not only the control of the spatial arrangement of cells but also the preservation of cell patterns over time. In this work, we developed a standing surface acoustic wave-based platform and demonstrated its capability for the well-controlled and rapid cell patterning of adipose-derived mesenchymal stem cells in a high-density homogenous collagen hydrogel. This biocompatible hydrogel is easily UV crosslinked and can be retrieved within 3 min. Acoustic waves successfully guided the cells toward pressure nodal lines, creating a contactless alignment of cells in <5 s in culture media and <1 min in the hydrogel. The acoustically patterned cells in the hydrogel did not show a decrease in cell viability (>90%) 48 h after acoustic induction. Moreover, 45.53% and 30.85% increases in metabolic activity were observed in growth and differentiation media, respectively, on Day 7. On Day 14, a 32.03% change in metabolic activity was observed using growth media, and no significant difference was observed using differentiation media. The alkaline phosphatase activity showed an increase of 80.89% and 24.90% on Days 7 and 14, respectively, for the acoustically patterned cells in the hydrogel. These results confirm the preservation of cellular viability and improved cellular functionality using the proposed high-resolution acoustic patterning technique and introduce unique opportunities for the application of stem cell regenerative patches for the emerging field of tissue engineering.