Engineered bacterial extracellular vesicles for osteoporosis therapy

Highlights

• Bacterial extracellular vesicles (BEVs) offer a novel mode of Gut-Bone axis.

• BEVs provide new insights for the treatment of osteoporosis.

• Engineered BEVs display great therapeutic potential for osteoporosis.

• The engineering strategies of modifying BEVs for osteoporosis were summarized.

Abstract

Osteoporosis (OP) is a systemic bone disease characterized by reduction of bone mass and destruction of structure, which can easily lead to fragility fractures. Over the past decade, an expanding body of study suggests that gut microbiota (GM) plays an important role in bone homeostasis and the pathogenesis of OP. The communication mechanism between GM and OP has received increasing attention. Bacterial extracellular vesicles (BEVs) are irreproducible phospholipid bilayer nanocarriers with sizes ranging from 20 to 400 nm, which can mediate the communication of gut and bone by delivering various bioactive molecules. BEVs have emerged as a promising platform for the treatment of OP due to their nanosized structures, low toxicity, drug loading capacity, good biocompatibility, ease of modification and industrialization. Here, we summarize the overview of BEVs, including biogenies, classes, structures, compositions, internalization, and isolation of BEVs. We then focus on the applications of natural BEVs in the treatment of OP. Subsequently, we present two major engineering strategies, including engineering parental strain and engineering BEVs after isolation, for modifying the BEVs for OP treatment. Finally, we provide an outlook on the major challenges and future prospects of BEVs in the OP treatment. We hope that the comprehensive understanding of natural and engineered BEVs will provide new solutions to OP treatment.