Magneto-mechanical actuation of magnetic responsive fibrous scaffolds boosts tenogenesis of human adipose stem cells

Abstract

Topographical cues of magnetically responsive tendon mimetic 3D scaffolds in combination with magneto-mechanical stimulation of human adipose stem cells synergistically boost their tenogenesis.

Remote triggering of TGF-β/Smad2/3 signaling in human adipose stem cells laden on magnetic scaffolds synergistically promotes tenogenic commitment

“…It was verified by Tomás AR et al an increase in nuclear YAP/TAZ, indicative of tension of the cytoskeleton which was likely caused by its adjustment to the external physical stimulus [11 , 43] . This mechanotransduction mechanism was suggested to boost hASCs tenogenic differentiation [11] , further supporting our results. Similarly, in our study, the more effective activation of TGF-β/Smad2/3 mechanism under AMF actuation, triggered the expression of target genes.…”

“…The expression of SCX and TNMD was higher in AMF stimulation conditions at 14 days ( p < 0.05). Magnetic field actuating on hASCs laden on magnetic fibrous scaffolds was shown to activate the transcriptional factors YAP and TAZ [11] , which upon activation are translocated to the nucleus, promoting stem cell differentiation. It was verified by Tomás AR et al an increase in nuclear YAP/TAZ, indicative of tension of the cytoskeleton which was likely caused by its adjustment to the external physical stimulus [11 , 43] .…”

“…Strategies applying magnetic stimuli combined with magnetic responsive scaffolds have shown positive outcomes in bone [8] , cardiac [9] , and vascular [10] TE. Our group has recently reported on magnetic responsive fibrous scaffolds for tendon TE, suggesting activation of YAP/TAZ signaling in response to magnetic stimulus [11] . These strategies may have an important role in tenogenic differentiation of stem cells [11][12][13][14] and/or in the modulation of the inflammatory response [15 , 16] , envisioning improved repair outcomes.…”

“…Our group has recently reported on magnetic responsive fibrous scaffolds for tendon TE, suggesting activation of YAP/TAZ signaling in response to magnetic stimulus [11] . These strategies may have an important role in tenogenic differentiation of stem cells [11][12][13][14] and/or in the modulation of the inflammatory response [15 , 16] , envisioning improved repair outcomes. Signaling cascades act as transducers of mechanical forces into downstream mechanosensory molecules.…”

In Vitro Innovation of Tendon Tissue Engineering Strategies

“…More recently, magnetically responsive fibrous scaffolds have been obtained with an aligned electrospun thread of PCL and cellulose nanocrystals coated with iron oxide magnetic nanoparticles. Magnetomechanical stimulation of hASCs promoted their tenogenic commitment with higher degrees of cell cytoskeleton anisotropic organization, increased expression of tendon-related markers, and a pro-healing inflammatory gene profile, compared to unstimulated samples [304]. Moreover, magnetic nanoparticles can be attached to the cell membrane, and specific receptors can be activated using Alternating Magnetic Fields (AMFs) [298,305,306].…”