Opa1-Knocked out EMSCs-Derived EV-Mito Empower Functionalized PEEK/LL37 Scaffolds to Combat Drug-Resistant Bone...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Infectious Diseases

Background:

• Bone defects with drug-resistant infections pose significant challenges due to antibiotic inefficacy and inflammation hindering bone regeneration.
• Current treatments struggle to address both bacterial infection and impaired osteogenesis simultaneously.

Purpose of the Study:

• To develop a novel scaffold-based therapeutic strategy for treating infected bone defects resistant to conventional antibiotics.
• To combine antimicrobial delivery with mitochondrial transfer to promote bone healing in a challenging infection model.

Main Methods:

• A sulfonated-PEEK scaffold (SPMiL) was engineered to co-deliver the antimicrobial peptide LL37 and mitochondria-rich extracellular vesicles (EV-Mito).
• EV-Mito were derived from ectomesenchymal stem cells (EMSCs) with Opa1 knockout to enhance vesicle production.
• The efficacy of SPMiL was evaluated in a MRSA-infected rat calvarial defect model.

Main Results:

• SPMiL demonstrated sustained release of LL37, effectively eradicating methicillin-resistant *Staphylococcus aureus* (MRSA).
• Transplanted functional mitochondria from EV-Mito promoted osteogenic differentiation and suppressed osteoclast activity.
• Mitochondrial transfer improved bone healing via metabolic reprogramming, antioxidant effects, and restored mitochondrial membrane potential.

Conclusions:

• The combination of antibacterial defense and mitochondrial transfer via the SPMiL scaffold presents a promising therapeutic strategy for infected bone defects.
• This approach overcomes limitations of conventional treatments by addressing both infection and impaired bone regeneration concurrently.