Injectable microgels loaded with programmable WELNs based on mendelian randomization macroanalysis alleviate...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Osteoarthritis Research

Background:

• Osteoarthritis (OA) poses a significant clinical challenge, demanding effective therapies for joint wear and cartilage regeneration.
• Plant-derived exosome-like nanovesicles (PELNs) show promise for disease intervention.
• Mendelian randomization identified watercress as a potential protective dietary factor against OA.

Purpose of the Study:

• To develop an injectable microgel system with synergistic therapeutic functions for osteoarthritis.
• To investigate the potential of watercress-derived exosome-like nanovesicles (WELNs) in OA treatment.
• To create a dual-action microgel combining mechanical lubrication and biological repair.

Main Methods:

• Mendelian randomization analysis to identify suitable PELNs for OA.
• Isolation and modification of watercress-derived exosome-like nanovesicles (WELNs) with chondrocyte affinity peptide (CAP).
• Encapsulation of WELNs-CAP into methacrylic anhydride modified hyaluronic acid (HAMA) to form injectable microgels (WELNs-CAP@HAMA).
• Evaluation of microgel lubrication, pain reduction, anti-inflammatory effects, mitochondrial function, and extracellular matrix (ECM) metabolism.
• Omics sequencing and structural biology to elucidate the mechanism of action.

Main Results:

• Developed injectable WELNs-CAP@HAMA microgels providing joint lubrication and pain reduction.
• Demonstrated sustained release of WELNs-CAP to improve mitochondrial dysfunction and ECM metabolism.
• Showed synergistic promotion of cartilage regeneration and repair.
• Identified ferulic acid (FA) in WELNs as a key component interacting with KLF10 to restore circadian rhythm and alleviate OA.

Conclusions:

• Successfully developed an injectable microgel system integrating mechanical lubrication and biological repair for OA treatment.
• The microgel system demonstrates significant potential for clinical transformation in managing osteoarthritis.
• The findings highlight the therapeutic efficacy of WELNs and their active component, ferulic acid, in OA management.