Applying microfluidic techniques for biomaterial and mechanical regulation of mesenchymal stem cells

Table 1 Microfluidic techniques for sorting and heterogeneity analysis of mesenchymal stem cells

Category	Method	Isolation principle	Discrimination parameters	Throughput	Advantages	Limitations	Ref.
Label-free sorting	Inertial microfluidics	Inertial lift and Dean drag forces	Cell size, shape	High	Label-free	Limited resolution for subtle biophysical differences	[14,16,25,28,29,31]
	Deterministic lateral displacement	Lateral deflection using micropillar arrays	Cell size, shape, deformability	High	Label-free	Limited resolution for subtle biophysical differences	[26,32,33]
	Dielectrophoresis	Non-uniform electric field	Dielectric properties, cell size	Low to medium	Label-free	Limited resolution for subtle biophysical differences	[27,34,36,37]
	Magnetophoresis	Magnetic field gradient	Magnetic susceptibility	Medium	Label-free	Limited resolution for subtle biophysical differences	[38,39]
	Acoustophoresis	Acoustic radiation forces	Cell density, compressibility, size	Medium	Label-free, gentle on cells	Limited resolution for subtle biophysical differences	[38,40,41]
Affinity-based sorting	Fluorescence-activated cell sorting	Fluorescent labeling & optical detection	Surface markers, fluorescence intensity	Relatively low	High specificity, multiparameter	Requires labeling	[44,47-49]
	Magnetic-activated cell sorting	Magnetic bead affinity	Surface marker expression	Medium	High specificity	Requires labeling	[43,50,51]
	Affinity capture	Surface ligand-receptor adhesion	Ligand binding kinetics	Very low	High specificity	Ligand activity loss	[52-54]

Table 2 Microfluidic techniques for mechanical stimulation of mesenchymal stem cells

Category	Microfluidic implementation	Key effects on MSCs	Ref.
Fluid shear stress	Passive (constant flow) or active (externally modulated) systems	(1) Low shear stress (10-5-10-2 dyn/cm2): Osteogenesis; (2) Medium shear stress (7.8-13.7 dyn/cm2): Endothelial differentiation; and (3) High shear stress (15 dyn/cm2): Adipogenesis	[85,87-90,99]
Cyclic stretch	Elastic membrane deformation	(1) Directs alignment; (2) Promotes proliferation, osteogenesis, and angiogenesis; and (3) High stretch (RMD > 3.5%) suppresses adipogenesis	[84,91,92]
Compressive stress	Fluidic pressure, confined microchannels, or mechanoactive hydrogels	(1) Promotes osteogenesis; and (2) Elevates vesicle secretion	[17,93-96,100]

MSCs: Mesenchymal stem cells; RMD: Relative membrane deformation.