Bone Regeneration Improves with Mesenchymal Stem Cell Derived Extracellular Vesicles (EVs) Combined with Scaffolds: A Systematic Review

Simple Summary Extracellular vesicles (EVs) have been recently considered one of the main characters for liquid biopsy (biomarkers) and therapeutic application. Particularly, the therapeutic application of EVs is involved in the bone regeneration, thanks to the regulation of immune environments, enhancement of angiogenesis, differentiation of osteoblasts and osteoclasts, and promotion of bone mineralization. In the past 15 years, researchers have focused on the application of EVs derived from different types of mesenchymal stem cells (MSCs) in the field of bone regenerative medicine. This systematic review aims to analyze in vitro and in vivo studies that report the effects of EVs combined with scaffolds in bone regeneration. A methodical review of the literature was performed on PubMed and Embase from 2012 to 2020. Sixteen papers were analyzed; of these, one study was in vitro, eleven were in vivo, and four were both in vitro and in vivo studies. This analysis shows a growing interest in this upcoming field, with overall positive results. Promising in vitro results have been discussed in terms of bone regeneration and pro-angiogenetic processes. The positive in vitro findings were confirmed in vivo, with studies showing positive effects on several critical-size defects. However, some aspects remain to be elucidated, like the different effects induced by EVs and secretome, the most suitable cell source, the EV production protocol and concentration, and the clinical use that may benefit from this new biological approach. Scaffolds associated with mesenchymal stem cell (MSC) derivatives, such as extracellular vesicles (EVs), represent interesting carriers for bone regeneration. This systematic review aims to analyze in vitro and in vivo studies that report the effects of EVs combined with scaffolds in bone regeneration. A methodical review of the literature was performed from PubMed and Embase from 2012 to 2020. Sixteen papers were analyzed; of these, one study was in vitro, eleven were in vivo, and four were both in vitro and in vivo studies. This analysis shows a growing interest in this upcoming field, with overall positive results. In vitro results were demonstrated as both an effect on bone mineralization and proangiogenic ability. The interesting in vitro outcomes were confirmed in vivo. Particularly, these studies showed positive effects on bone regeneration and mineralization, activation of the pathway for bone regeneration, induction of vascularization, and modulation of inflammation. However, several aspects remain to be elucidated, such as the concentration of EVs to use in clinic for bone-related applications and the definition of the real advantages.

Automated summary

EVs are considered crucial in liquid biopsy and therapeutic applications, particularly in the field of bone regeneration. Over the past 15 years, researchers have focused on the application of EVs from MSCs in bone regenerative medicine. Positive results have been found in both in vitro and in vivo studies, but some questions remain to be elucidated.