Synthetically Engineered Bacterial Extracellular Vesicles and IL-4-Encapsulated Hydrogels Sequentially Promote...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Synthetic Biology

Background:

• Osteoporosis (OP) causes bone fragility and fractures (OPF), with current treatments having limited efficacy and side effects.
• Bacterial extracellular vesicles (BEVs) engineered via synthetic biology show promise as a safe alternative for OPF treatment.

Purpose of the Study:

• To develop and evaluate a novel biomaterial for osteoporotic fracture repair.
• To investigate the combined effects of IL-4 and engineered BEVs (BEVs-BP) in a GelMA hydrogel (IL-4/BEVs-BP@GelMA) for enhanced bone regeneration.

Main Methods:

• Constructed bioengineered BEVs loaded with pBMP-2-VEGF (BEVs-BP).
• Encapsulated BEVs-BP with IL-4 in GelMA hydrogels to create IL-4/BEVs-BP@GelMA.
• Assessed *in vitro* effects on macrophage polarization, osteogenesis, and angiogenesis.
• Evaluated *in vivo* bone organoid maturation and mineralization, and osteoporotic fracture repair in mice.

Main Results:

• IL-4 modulated immune cells to alleviate inflammation, while BEVs-BP upregulated BMP-2 and VEGF for osteogenesis and vascularization.
• IL-4/BEVs-BP@GelMA promoted M1 to M2 macrophage polarization, enhanced osteogenesis, and increased angiogenesis *in vitro*.
• BEVs-BP promoted bone organoid maturation and mineralization *in vivo*, accelerating osteoporotic fracture repair in mice.

Conclusions:

• IL-4/BEVs-BP@GelMA is an effective biomaterial for osteoporotic fracture management.
• This approach offers a promising therapeutic strategy by combining anti-inflammatory and bone-regenerative properties.
• The developed hydrogel system provides a powerful and easily constructible solution for bone repair.