TRPV4 Activator-Containing CMT-Hy Hydrogel Enhances Bone Tissue Regeneration In Vivo by Enhancing Mitochondrial...

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Regenerative Medicine

Background:

• Treating bone defects is challenging, costly, and time-consuming.
• Mesenchymal stem cells (MSCs) are crucial for bone regeneration.
• Transient Receptor Potential Vanilloid 4 (TRPV4) channels regulate cellular functions in MSCs.

Purpose of the Study:

• To investigate the role of TRPV4 in MSCs for bone defect treatment.
• To develop and evaluate a novel hydrogel scaffold (CMT-Hy) incorporating TRPV4 modulators.
• To assess the efficacy of the developed scaffold in promoting bone regeneration.

Main Methods:

• MSCs were encapsulated in carboxymethyl tamarind hydrogel (CMT-Hy) modified with TRPV4 activator (4αPDD).
• Cellular parameters including morphology, Ca2+, ROS, NO, mitochondrial health, differentiation, and biomineralization were analyzed.
• In vivo studies evaluated scaffold biocompatibility and bone defect repair in a rat femur model.

Main Results:

• The 4α-50-CMT-Hy hydrogel modulated MSCs' cell morphology, Ca2+ levels, and mitochondrial function (ATP, cardiolipin, membrane potential).
• TRPV4 activation via 4α-50-CMT-Hy enhanced in vitro cell differentiation and biomineralization.
• The scaffold demonstrated no in vivo toxicity and significantly improved bone defect repair in rats.

Conclusions:

• TRPV4 plays a critical role in regulating MSC function and bone regeneration.
• The 4α-50-CMT-Hy hydrogel is a promising, non-toxic scaffold for enhancing bone defect repair.
• This low-cost scaffold holds potential for clinical applications in treating large-scale bone defects.