Modulation of RhoA/ROCK-YAP/TAZ Axis enhances in situ adipogenesis in decellularized adipose-derived matrix hydrogels

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Large-area soft tissue reconstruction is a significant challenge in plastic surgery.
• Decellularized adipose matrix (DAM) shows potential for adipose tissue regeneration but often results in fibrotic tissue formation.
• Mechanical signaling pathways, particularly RhoA/ROCK-YAP/TAZ, are crucial for cell differentiation.

Purpose of the Study:

• To investigate the efficacy of modulating the RhoA/ROCK-YAP/TAZ axis using the ROCK inhibitor Y-27632 within DAM hydrogels for enhanced adipose tissue regeneration.
• To evaluate the in vitro and in vivo performance of Y-27632 loaded DAM hydrogels for soft tissue reconstruction.

Main Methods:

• Decellularization of adipose tissue to create DAM scaffolds.
• Preparation of temperature-sensitive DAM hydrogels loaded with Y-27632.
• In vitro co-culture of adipose-derived stem cells (ADSCs) with loaded hydrogels.
• Assessment of ADSC differentiation and phenotype.
• In vivo subcutaneous implantation in a mouse model to evaluate adipogenesis.

Main Results:

• Successfully prepared decellularized adipose matrix hydrogels with sol-gel transition properties.
• Demonstrated good cytocompatibility and promotion of adipogenic differentiation of ADSCs in vitro.
• Showed reversal of myofibroblast differentiation by inhibiting the RhoA/ROCK-YAP/TAZ axis.
• Induced significant in situ adipogenesis in a subcutaneous mouse model.
• Confirmed enhanced adipogenic efficiency of DAM scaffolds loaded with Y-27632.

Conclusions:

• Loading DAM hydrogels with Y-27632 effectively enhances adipogenesis and promotes adipose tissue regeneration.
• This approach offers a promising cell-free strategy for soft tissue reconstruction by regulating cell fate.
• The integration of DAM with mechanical signaling modulation presents new avenues for in situ tissue regeneration and restoration of large-volume soft tissue defects.