Engineering exosomes and biomaterial-assisted exosomes as therapeutic carriers for bone regeneration

Abstract

Mesenchymal stem cell-based therapy has become an effective therapeutic approach for bone regeneration. However, there are still limitations in successful clinical translation. Recently, the secretome of mesenchymal stem cells, especially exosome, plays a critical role in promoting bone repair and regeneration. Exosomes are nanosized, lipid bilayer-enclosed structures carrying proteins, lipids, RNAs, metabolites, growth factors, and cytokines and have attracted great attention for their potential application in bone regenerative medicine. In addition, preconditioning of parental cells and exosome engineering can enhance the regenerative potential of exosomes for treating bone defects. Moreover, with recent advancements in various biomaterials to enhance the therapeutic functions of exosomes, biomaterial-assisted exosomes have become a promising strategy for bone regeneration. This review discusses different insights regarding the roles of exosomes in bone regeneration and summarizes the applications of engineering exosomes and biomaterial-assisted exosomes as safe and versatile bone regeneration agent delivery platforms. The current hurdles of transitioning exosomes from bench to bedside are also discussed.

Keywords: Biomaterial-assisted exosomes; Bone regeneration; Exosome engineering; Exosomes; Mesenchymal stem cells; Preconditioning.

Fig. 1

Exosomes derived from MSCs as a delivery vehicle have the advantages of low immunogenicity, easily uptaken by cells, easily crossing biological barriers, cargo protection from degradation, easily loading therapeutics, high cargo release stability, high biocompatibility, long circulation, and having the ability of tissue targeting. Therefore, they have been developed as a novel strategy for treating various diseases

Fig. 2

The avenues for the modification of exosomes are mainly divided into two aspects: preconditioning of parental cells and exosome engineering. Preconditioning of parental cells for bone regeneration mainly included hypoxic preconditioning, cytokine preconditioning and chemical preconditioning. Exosome engineering is mainly divided into two categories: cargo packaging into exosomes and surface modification of exosomes

Fig. 3

Exosomes can bind to biomaterial scaffolds, including metal materials, bioactive ceramics, hydrogels and synthetic polymers, and then target injured sites to enhance bone regeneration mainly by inducing osteogenesis and angiogenesis