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Synthetically Engineered Bacterial Extracellular Vesicles and IL-4-Encapsulated Hydrogels Sequentially Promote
Guangyin Zhou1,2,3,4, Qirong Zhou5, Ruiyang Li5
1Institute of Translational Medicine, Shanghai University, Shanghai 200444, China.
Abstract:
Osteoporosis (OP) is a systemic disease characterized by decreased bone density and quality, leading to fragile bones and osteoporotic fractures (OPF). Conventional treatments for OPF often exhibit limited therapeutic efficacy and significant side effects. Synthetic biology-based bacterial extracellular vesicles (BEVs) offer a safe and effective alternative for OPF treatment. Here, we constructed bioengineered BEVs loaded with pBMP-2-VEGF (BEVs-BP) and encapsulated them together with IL-4 in GelMA hydrogels to form IL-4/BEVs-BP@GelMA. Initially, IL-4 alleviated chronic inflammation by modulating immune cells, while BEVs-BP subsequently enhanced osteogenesis and vascularization by upregulating BMP-2 and VEGF expression. In vitro, IL-4/BEVs-BP@GelMA polarized M1 macrophages toward the M2 phenotype, enhanced osteogenesis, and increased angiogenesis. Moreover, BEVs-BP effectively promoted the maturation and mineralization of bone organoids in vivo. Finally, IL-4/BEVs-BP@GelMA successfully accelerated osteoporotic fracture repair in mice. In summary, we developed an easy-to-build and powerful bone repair biomaterial, IL-4/BEVs-BP@GelMA, which offers a therapeutic strategy for osteoporotic fracture management.
Insights
This study presents a novel biomaterial for treating osteoporotic fractures. The IL-4/BEVs-BP@GelMA hydrogel effectively promotes bone repair by reducing inflammation and enhancing bone formation and vascularization.
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.
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