The Delivery of Extracellular Vesicles Loaded in Biomaterial Scaffolds for Bone Regeneration.

Hui-Chun Yan,Jing Li,Ting Zhang,Da-Wei Liu,Qian Li,Lin-Chuan Wang,Yi-Qiang Qiao,Yan-Heng Zhou,Ting-Ting Yu

doi:10.3389/fbioe.2020.01015

Abstract

Extracellular vesicles (EVs) are heterogeneous nanoparticles actively released by cells that comprise highly conserved and efficient systems of intercellular communication. In recent years, numerous studies have proven that EVs play an important role in the field of bone tissue engineering (BTE) due to several advantages, such as good biosafety, stability and efficient delivery. However, the application of EVs therapies in bone regeneration has not been widely used. One of the major challenges for the application of EVs is the lack of sufficient scaffolds to load and control the release of EVs. Thus, in this review, we describe the most advanced current strategies for delivering EVs with various biomaterials for the use in bone regeneration, the role of EVs in bone regeneration, the distribution of EVs mediated by biomaterials and common methods of promoting EVs delivery efficacy with a focus on biomaterial properties.

Highlights

Extracellular vesicles (EVs) are membrane-encapsulated heterogeneous particles actively released by cells that comprise highly conserved and efficient systems of intercellular communication
Several recent reviews have focused on EV application in tissue regeneration as well as the involved mechanisms of EVs (Chen et al, 2017; Silva et al, 2017; Taverna et al, 2017; Keshtkar et al, 2018; Li Q. et al, 2018; Chu et al, 2019), our review focuses on the controlled release of EVs loaded in scaffolds and provides a discussion of the existing and potential modifications of EVs delivery systems for bone tissue engineering (BTE) (Figure 1)
Li W. et al (2018) achieved the accelerated restoration of calvarial bone defects in a mouse model by integrating exosomes derived from human adipose-derived stem cells with polydopamine (PDA)-coated poly/(PLGA) scaffolds, which resulted in timed release and enhanced bioactivities

Summary

INTRODUCTION

Extracellular vesicles (EVs) are membrane-encapsulated heterogeneous particles actively released by cells that comprise highly conserved and efficient systems of intercellular communication. The underlying mechanisms of the osteogenic effects of EVs remain unclear, EVs have been shown to play a role in cellular signaling and the molecular transport of bone by regulating the immune microenvironment, promoting angiogenesis, balancing bone metabolism, and participating in mineralization Their protective effects in hypoxic and ischemic conditions (Figure 3; Hugel et al, 2005; Liu X. et al, 2017a; Jin et al, 2019), and endogenous MSC recruitment in bone regeneration cannot be ignored (Furuta et al, 2016). In another study, Li W. et al (2018) achieved the accelerated restoration of calvarial bone defects in a mouse model by integrating exosomes derived from human adipose-derived stem cells (hASCs) with polydopamine (PDA)-coated poly (lacticcoglycolic acid)/(PLGA) scaffolds, which resulted in timed release and enhanced bioactivities This in vitro cell-free system showed that stimulated osteoinductive effects were favorable in improving the proliferation, migration and homing of MSCs in new bone. To achieve improved osteogenic properties, modifications of EV/biomaterial osteogenic systems need to be further explored

METHODS

Findings

LIMITATIONS AND FUTURE