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This communication reports the first comparative study addressing the effects of both structural architecture and mechanical loading on human mesenchymal stem cells (hMSC) positioned at the interface of a 3D in vitro model composed of a nanofibre/hydrogel laminate composite. hMSC phenotype was affected by both stimuli over a seven-day period. Cells were orientated parallel to the underlying fibre direction irrespective of environment (electrospun 2D fibre sheet or laminate 2D sheet with collagen gel layer). Application of cyclical tensile force (5% strain, 1 Hz, 1 h per day) encouraged hMSCs to remain at the fibre/gel interface, whereas cells cultured in static conditions migrated from the interface to the upper hydrogel layer. Depending on the stimulus applied, hMSCs presented an up-regulation in gene expression, indicative of several cell lineages, with those cultured at the interface and physically stimulated expressing markers indicative of angiogenesis, osteogenesis, and tenogenesis. This study highlights the importance of developing biomaterial scaffolds with environmental cues to specifically drive cells towards the tissue intended for bioengineering.

Effect of Topography and Physical Stimulus on hMSC Phenotype Using a 3D In Vitro Model