In vitro phenotypically stable cartilage regeneration with mechanically adaptable microenvironment using a...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Cartilage injuries pose significant clinical challenges for regenerative repair.
• Hydrogel scaffolds offer a promising strategy for cartilage defect treatment.
• Existing in vitro methods face issues with nutrient transport and maintaining cartilage phenotype.

Purpose of the Study:

• To present an in vitro hydrostatic pressure (HP) bioreactor method using porous hydrogel scaffolds.
• To accelerate phenotypically stable cartilage regeneration.
• To explore the underlying mechanisms of HP-mediated cartilage repair.

Main Methods:

• Fabrication of 3D-printed porous gelatin/chondroitin sulfate composite hydrogel scaffolds.
• Application of a hydrostatic pressure (HP) bioreactor for in vitro cartilage pre-culture.
• Analysis of mechanosensitive channel activation (TRPV4, PIEZO1) and downstream signaling (Ca2+ - SOX9).
• In vivo evaluation using goat models.

Main Results:

• HP stimulation upregulated TRPV4 and PIEZO1, initiating a Ca2+-dependent mechanical transduction pathway.
• Mechanical signals promoted chondrogenesis while suppressing hypertrophy and ossification.
• In vitro HP-preconditioned constructs demonstrated successful long-term regeneration in vivo.

Conclusions:

• HP stimulation via a novel bioreactor effectively regulates phenotypically stable cartilage regeneration.
• The study elucidates the mechanism of HP-mediated mechanotransduction in cartilage repair.
• This approach presents a promising strategy for clinical cartilage defect treatment.