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Applying a Three-dimensional Uniaxial Mechanical Stimulation Bioreactor System to Induce Tenogenic Differentiation of Tendon-Derived Stem Cells
Published on: August 1, 2020
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Engineering a Mechanoactive Fibrous Substrate with Enhanced Efficiency in Regulating Stem Cell Tenodifferentiation
Xuran Guo1,2, Xianliu Wang1,2, Han Tang1,2
1College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
ACS Applied Materials & Interfaces
|May 11, 2022
Summary
This study developed shape-memory PLCL fibers that self-stimulate stem cells for tendon differentiation. The mechanoactive fibers enhanced tenogenic markers and gene expression without external forces, improving tendon tissue engineering.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Stem Cell Biology
Background:
- Aligned electrospun fibers show limited capacity in driving stem cell tenogenic differentiation.
- Tendon's mechanoactive nature suggests self-generated mechanical stimuli can enhance tenogenic induction.
- Existing methods often require external forces or specific supplements for effective tenogenic differentiation.
Purpose of the Study:
- To investigate if self-actuating mechanoactive aligned fibrous structures can potentiate tenogenic induction of stem cells.
- To assess the impact of constrained shape recovery stress on human adipose-derived stem cells (ADSCs) cultured on programmed poly(l-lactide-co-caprolactone) (PLCL) fibers.
- To explore the underlying mechanisms of enhanced tenogenic differentiation.
Main Methods:
- Electrospinning of poly(l-lactide-co-caprolactone) (PLCL) into aligned fibrous structures.
- Shape-programming via a "stretching-recovery" procedure to impart shape memory capability.
- Culture of human adipose-derived stem cells (ADSCs) on programmed PLCL substrates for 7 days without tenogenic supplements.
- Analysis of cell morphology, proliferation, tenogenic protein markers (TNMD, TNC), gene expression (SCX, TNMD, TNC, COL I), and signaling pathways (Rho/ROCK).
Main Results:
- The shape memory effect (SME) and resultant in situ mechanical stimulus did not adversely affect cell viability or proliferation.
- Significant cellular elongation along the fiber alignment direction was observed.
- Upregulation of tendon-specific protein markers (tenomodulin, tenascin-C) and gene expression (scleraxis, tenomodulin, tenascin-C, collagen I) was noted.
- The Rho/ROCK signaling pathway was identified as mechanistically involved in enhanced tenodifferentiation.
Conclusions:
- Constrained shape recovery stress from self-actuating fibrous substrates can effectively regulate stem cell tenodifferentiation.
- This approach combines topographical cues with intrinsic mechanoactivity, offering an innovative loading modality for tendon tissue engineering.
- The demonstrated paradigm holds promise for improving tendon healing and regeneration strategies.
