Modulation of Local Overactive Inflammation via Injectable Hydrogel Microspheres

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Injectable hydrogel microspheres show promise for clinical applications.
• Overactive local inflammation can hinder biomaterial efficacy in degenerative diseases.

Purpose of the Study:

• To construct an injectable "peptide-cell-hydrogel" microsphere system.
• To inhibit inflammatory cytokine storms and regulate extracellular matrix (ECM) metabolic balance.
• To evaluate the therapeutic potential in a rat model of intervertebral disc degeneration.

Main Methods:

• Covalent coupling of APETx2 peptide to hydrogel microspheres.
• Loading of nucleus pulposus cells into the microspheres.
• In vitro assessment of biocompatibility and controlled release of APETx2 in acidic conditions.
• In vivo delivery of microspheres to rat degenerative intervertebral discs.

Main Results:

• Covalent coupling of APETx2 maintained microsphere biocompatibility.
• Controlled release of APETx2 observed for over 28 days in acidic environments.
• Significant reduction in ASIC-3 (3.53-fold) and IL-1β (7.29-fold) expression in vivo.
• Significant recovery of ECM content observed at 8 weeks post-treatment.

Conclusions:

• The "peptide-cell-hydrogel" microsphere system effectively inhibits inflammation.
• This approach promotes tissue regeneration in degenerative conditions with overactive inflammatory responses.
• The strategy offers a promising therapeutic avenue for degenerative diseases.