Dynamic vibration cooperates with connective tissue growth factor to modulate stem cell behaviors

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cell Biology

Background:

• Vocal fold disorders impact millions, necessitating advanced repair strategies.
• Tissue engineering offers a promising alternative to traditional vocal fold repair methods.
• Developing functional vocal fold tissue requires mimicking its unique microenvironment.

Purpose of the Study:

• To investigate the combined effects of vibratory stimulation and connective tissue growth factor (CTGF) on mesenchymal stem cells (MSCs).
• To induce MSCs to differentiate into vocal fold fibroblast (VFF)-like cells within a biomimetic scaffold.
• To understand the underlying molecular mechanisms, including MAPK pathways, involved in this differentiation process.

Main Methods:

• MSCs were cultured on poly(ɛ-caprolactone) (PCL) scaffolds.
• Cells underwent sequential 3-day treatments of high-frequency vibratory stimulation followed by CTGF.
• Key extracellular matrix components and cellular responses were analyzed using molecular assays.

Main Results:

• Vibratory stimulation increased hyaluronic acid, tenascin-C, decorin, and MMP1 production.
• CTGF enhanced tenascin-C and decorin production, while CTGF alone boosted collagen I and sulfated glycosaminoglycans.
• Combined treatment maximized MMP1, tenascin-C, collagen III, and decorin synthesis, with differential effects on elastin, HAS1, and FSP-1.

Conclusions:

• Sequential vibratory and CTGF treatments effectively coax MSCs toward a VFF-like phenotype.
• The Erk1/2 MAPK pathway is crucial for mediating these mechano-biochemical responses.
• This approach accelerates vocal fold matrix synthesis and remodeling, paving the way for improved tissue engineering strategies.