# Engineered Pseudomonas mirabilis-Derived Outer Membrane Vesicles Targeting Bone Microenvironment to Improve Osteoporosis

## TL;DR

This study explores using engineered bacterial vesicles to target bone health and treat osteoporosis safely.

## Contribution

The novel use of Pseudomonas mirabilis-derived OMVs with bone-targeting peptides for osteoporosis treatment is introduced.

## Key findings

- PM-OMVs-BT showed strong bone-targeting abilities and safety in vivo.
- LGG-OMVs-BT promoted osteogenic differentiation and mineralization in bone marrow stromal cells.
- The system delivered endogenous miRNAs effectively to the bone microenvironment.

## Abstract

Introduction: Osteoporosis (OP) is a prevalent condition marked by reduced bone density and a heightened risk of fractures. Current treatments often have side effects, underscoring the need for safer alternatives. Recent research highlights the significant role of gut microbiota and their metabolites in maintaining bone health. Notably, bacterial outer membrane vesicles (OMVs) have emerged as a promising platform due to their nanoscale sizes, low toxicity, drug-loading capabilities, and excellent biocompatibility. Methods: In this study, we developed a delivery system using OMVs derived from Pseudomonas mirabilis (PM). By anchoring bone-targeting peptides to the PM-OMVs membrane, we equipped these vesicles to deliver endogenous miRNAs to the bone microenvironment effectively. Results and Discussion: The bone-targeted PM-OMVs (PM-OMVs-BT) demonstrated exceptional bone-targeting abilities and exhibited a favorable safety profile in vivo. Additionally, LGG-OMVs-BT were successfully internalized by bone marrow stromal cells (BMSCs) without significant cytotoxicity, effectively promoting their osteogenic differentiation and mineralization. In conclusion, our study indicates that PM-OMVs-BT could offer a safe and effective treatment option for OP.