Polysaccharide nanofibers with variable compliance for directing cell fate

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Tissue Engineering

Background:

• Cells respond to physical and mechanical cues from their microenvironment, including extracellular matrix topography and stiffness.
• Controlling these cues is crucial for directing cell fate and function in regenerative medicine applications.

Purpose of the Study:

• To develop and characterize polysaccharide nanofibers with tunable stiffness for directing stem cell differentiation.
• To investigate the effect of scaffold stiffness on the neuronal commitment of human first trimester mesenchymal stem cells (fMSCs).

Main Methods:

• Fabrication of pullulan/dextran (P/D) nanofibers with varying stiffness via in situ crosslinking during electrospinning.
• Characterization of scaffold mechanical properties using atomic force microscopy and tensile testing.
• Assessment of fMSC differentiation towards motor neurons on P/D scaffolds with different stiffnesses, including gene and protein expression analysis.

Main Results:

• P/D nanofibers with tunable stiffness (Young's modulus ranging from 7.19 to 11.08 kPa) were successfully fabricated.
• fMSCs cultured on STMP14 scaffolds (7.84 kPa) showed the greatest extent of neuronal differentiation, with morphological changes and increased motor neuron marker expression.
• Enhanced expression of choline acetyltransferase was observed on STMP14 and STMP16 scaffolds compared to STMP12.

Conclusions:

• Scaffold stiffness can be effectively modulated by controlling the crosslinking density during electrospinning of P/D nanofibers.
• Optimized P/D nanofiber stiffness supports and promotes the neuronal commitment of fMSCs.
• These tunable polysaccharide nanofibers show promise for applications in neural tissue engineering and regenerative medicine.