Mechano-Piezoelectric F-Peptide Hydrogels Enable In Situ Stem Cell and Immune Niche Modulation for Cartilage Regeneration

Osteoarthritis, a condition marked by cartilage degeneration and synovial inflammation, has driven research into bio-hydrogel therapies. Current methods, however, do not provide adequate piezoelectric output, nor do they effectively target both cartilage and inflammation. To overcome these limitations, researchers developed a unique mechano-piezoelectric peptide hydrogel.

This gel is composed of nanofibers that incorporate piezoelectric cues and recruit mesenchymal stromal cells (MSCs), facilitating their recruitment and the activation of PIEZO2 mechanosignaling.

The hydrogel's seed peptide possesses four key functions: targeting COL2A1, responding to MMP-13, promoting MSCs homing, and self-assembly. Elevated levels of MMP-13 in the osteoarthritis environment trigger gelation, which aids in the recruitment of MSCs and ensures drug retention. The mechanical and piezoelectric properties of the gel are enhanced through fluorination, a process that modifies the hierarchical nanofiber assembly. This is supported by detailed morphological, biophysical, and computational analysis.

A formulation of this hydrogel, loaded with trifluoromethyl-modified 4-octyl itaconate (4-OI), effectively reverses osteoarthritis. This is achieved through the activation of PI3K/AKT pathways and suppression of Wnt/{beta}-catenin signaling. The treatment leads to improved Osteoarthritis Research Society International (OARSI) scores, better bone microarchitecture, and an enhanced cartilage matrix. The combination of mechano-piezoelectric cues and 4-OI presents a clinically promising approach to treating osteoarthritis.