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

Abstract

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.

Wired for Success: Probing the Effect of Tissue-Engineered Neural Interface Substrates on Cell Viability

“…However, the addition of GO to GelMA enhances this response, with GelMA-GO (striped pink) showing the most significant increase under both passive and stimulation regimes indicating a consistent enhancement independent of stimulation. 78 By day 3, cells across all hydrogels show enhanced metabolic activity under stimulation, suggesting either enhanced cell proliferation or increased metabolic functioning. 79 On day 7, the overall increase in metabolic activity under stimulation remains consistent, indicating a potential stimulation effectiveness over prolonged periods.…”

Acoustofluidics – changing paradigm in tissue engineering, therapeutics development, and biosensing

“…Martinez Villegas et al 142 demonstrated the enhancement of the osteogenic differentiation and proliferation of adipose-derived stem cells embedded into a photocurable hydrogel via acoustic patterning using a frequency of 13.11 MHz (SSAW). Furthermore, Devendran et al 143 scrutinized the phenotypes of four distinct human and mouse cell lines after exposure to 48.5 MHz (SAW).…”

Three‐dimensional multicellular biomaterial platforms for biomedical application

“…In fact, there is increasing evidence that preparing cells as 3D tissue-like structures with a certain spatial structure enhances their secretory activity. [62] This may be related to the formation of more cell-cell and cell-ECM interactions, [74,75] as well as cell responses to changes in spatial curvature. [76] The distinct advantage of cell sheets over spheroids in the field of tissue engineering is that cell sheets can be relatively easily combined into macrostructures, so that scaffold-free multicellular platforms with multiple repair functions can be prepared.…”

“…[79] Because the relationship between cells is much closer to that of tissues, the cell behavior and growth reflected by the cells in cell sheets can better reflect the actual physiological situation. To reproduce the distribution of cells in complex tissues as much as possible, many researchers have used micropattern, [84,85] microcontact printing, [86] magnetic or acoustic control, [75,87] and other methods to regulate cell distribution and explore the crosstalk between different cells in complex models. However, the structural complexity obtained by these methods is still not enough.…”