Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention as promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer and are secreted by various cells. Due to their high biocompatibility, stability, and low immunogenicity, exosomes are favored as cargo carriers. The lipid bilayer membrane of exosomes also offers protection against cargo degradation, making them a desirable candidate for drug delivery. However, loading cargo into exosomes remains to be a challenge. Despite various strategies such as incubation, electroporation, sonication, extrusion, freeze–thaw cycling, and transfection that have been developed to facilitate cargo loading, inadequate efficiency still persists. This review offers an overview of current cargo delivery strategies using exosomes and summarizes recent approaches for loading small-molecule, nucleic acid, and protein drugs into exosomes. With insights from these studies, we provide ideas for more efficient and effective delivery of drug molecules by using exosomes.

/pdf/current-strategies-for-exosome-cargo-loading-and-targeting-11ciqmtj.pdf

Current Strategies for Exosome Cargo Loading and Targeting Delivery

https://doi.org/10.1016/j.bioactmat.2023.05.018

M2 macrophage-derived exosomes promote diabetic fracture healing by acting as an immunomodulator

Bone/cartilage organoid on-chip: Construction strategy and application.

Osteoporosis is a systemic skeletal disease characterized by decreased bone mass, destruction of bone microstructure, raised bone fragility, and enhanced risk of fractures. The correlation between gut microbiota and bone metabolism has gradually become a widespread research hotspot in recent years, and successive studies have revealed that the alterations of gut microbiota and its-related metabolites are related to the occurrence and progression of osteoporosis. Moreover, several emerging studies on the relationship between gut microbiota-related metabolites and bone metabolism are also underway, and extensive research evidence has indicated an inseparable connection between them. Combined with latest literatures and based on inextricable connection of gut-bone axis, this review is aimed to summarize the relation, potential mechanisms, application strategies, clinical application prospects, and existing challenges of gut microbiota and its-related metabolites on osteoporosis, thus updating the knowledge in this research field and providing certain reference for future researches. 

Targeting the gut microbiota-related metabolites for osteoporosis: The inextricable connection of gut-bone axis

As an emerging cell-free therapy, exosomes derived from stem cells have been widely explored for tissue regeneration. However, it is still a great challenge to achieve the engineering extraction of bone-functionalized exosomes and their sustained delivery in tissue defects. Herein, a novel bone morphogenetic protein 2 (BMP2)-overexpressed engineered exosomes-loaded GelMA hydrogel was rationally constructed for in-situ bone regeneration. BMP2-overexpressed exosomes were engineering prepared using mouse embryonic fibroblasts (NIH-3T3) as tool cells via gene manipulations and ultracentrifugation techniques. The sustained delivery of exosomes in cranial defects was achieved by loading GelMA biodegradable hydrogel. In addition, the pre-prepared BMP2-overexpressed exosome-loaded GelMA hydrogel showed excellent porous structure, rheological property and biocompatibility. In vitro biological results indicated that BMP2-overexpressed exosomes significantly promoted proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs). In vivo animal experiments analysis revealed BMP2-overexpressed exsomes-laden biodegradable hydrogel effectively improved in situ bone regeneration via mice cranial defect model. Overall, this study provided a promising cell-free therapy of engineered exosomes-loaded biodegradable hydrogel for treating bone defects. 

Engineering preparation and sustained delivery of bone functional exosomes-laden biodegradable hydrogel for in situ bone regeneration

http://www.cell.com/article/S2666379122004451/pdf

Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases

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Exosome-based bone-targeting drug delivery alleviates impaired osteoblastic bone formation and bone loss in inflammatory bowel diseases