Exosome-Laden Hydrogels: A Novel Cell-free Strategy for <i>In-situ</i> Bone Tissue Regeneration

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Abstract

In-situ bone tissue regeneration, which harnesses cell external microenvironment and their regenerative potential to induce cell functions and bone reconstruction through some special properties of biomaterials, has been deeply developed. In which, hydrogel was widely applied due to its 3D network structure with high water absorption and mimicking native extracellular matrix (ECM). Additionally, exosomes can participate in a variety of physiological processes such as cell differentiation, angiogenesis and tissue repair. Therefore, a novel cell-free tissue engineering (TE) using exosome-laden hydrogels has been explored and developed for bone regeneration in recent years. However, related reviews in this field are limited. Therefore, we elaborated on the shortcomings of traditional bone tissue engineering, the challenges of exosome delivery and emphasized the advantages of exosome-laden hydrogels for in-situ bone tissue regeneration. The encapsulation strategies of hydrogel and exosomes are listed, and the research progress and prospects of bioactive hydrogel composite system for continuous delivery of exosomes for in-situ bone repair are also discussed in this review.

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Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)

Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).

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Regulation of immune responses by extracellular vesicles.

Paul Robbins, Adrian Morelli (2014)

Extracellular vesicles, including exosomes, are small membrane vesicles derived from multivesicular bodies or from the plasma membrane. Most, if not all, cell types release extracellular vesicles, which then enter the bodily fluids. These vesicles contain a subset of proteins, lipids and nucleic acids that are derived from the parent cell. It is thought that extracellular vesicles have important roles in intercellular communication, both locally and systemically, as they transfer their contents, including proteins, lipids and RNAs, between cells. Extracellular vesicles are involved in numerous physiological processes, and vesicles from both non-immune and immune cells have important roles in immune regulation. Moreover, extracellular vesicle-based therapeutics are being developed and clinically tested for the treatment of inflammatory diseases, autoimmune disorders and cancer. Given the tremendous therapeutic potential of extracellular vesicles, this Review focuses on their role in modulating immune responses, as well as their potential therapeutic applications.

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Progress in Exosome Isolation Techniques

Pin Li, Melisa Kaslan, Sze Lee … (2017)

Exosomes are one type of membrane vesicles secreted into extracellular space by most types of cells. In addition to performing many biological functions particularly in cell-cell communication, cumulative evidence has suggested that several biological entities in exosomes like proteins and microRNAs are closely associated with the pathogenesis of most human malignancies and they may serve as invaluable biomarkers for disease diagnosis, prognosis, and therapy. This provides a commanding impetus and growing demands for simple, efficient, and affordable techniques to isolate exosomes. Capitalizing on the physicochemical and biochemical properties of exosomes, a number of techniques have been developed for the isolation of exosomes. This article summarizes the advances in exosome isolation techniques with an emphasis on their isolation mechanism, performance, challenges, and prospects. We hope that this article will provide an overview of exosome isolation techniques, opening up new perspectives towards the development more innovative strategies and devices for more time saving, cost effective, and efficient isolations of exosomes from a wide range of biological matrices.

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Author and article information

Contributors

Jinru Sun: URI : https://loop.frontiersin.org/people/1616018/overview

Xiuhui Wang: URI : https://loop.frontiersin.org/people/1122774/overview

Jiacan Su: URI : https://loop.frontiersin.org/people/462733/overview

Journal

Journal ID (nlm-ta): Front Bioeng Biotechnol

Journal ID (iso-abbrev): Front Bioeng Biotechnol

Journal ID (publisher-id): Front. Bioeng. Biotechnol.

Title: Frontiers in Bioengineering and Biotechnology

Publisher: Frontiers Media S.A.

ISSN (Electronic): 2296-4185

Publication date (Electronic): 01 April 2022

Publication date Collection: 2022

Volume: 10

Electronic Location Identifier: 866208

Affiliations

[1] ¹ Institute of Translational Medicine , Shanghai University , Shanghai, China

[2] ² Department of Orthopedics , Shanghai Zhongye Hospital , Shanghai, China

[3] ³ Department of Orthopaedics Trauma , Changhai Hospital , Second Military Medical University , Shanghai, China

Author notes

Edited by: Di Huang, Taiyuan University of Technology, China

Reviewed by: Ying Yang, University of Michigan, United States

Jingchao Li, Donghua University, China

Chen Yang, Wenzhou Institute (CAS), China

*Correspondence: Xiuhui Wang, blackrabbit@ 123456shu.edu.cn ; Jiacan Su, drsujiacan@ 123456163.com

[ † ]

These authors have contributed equally to this work

This article was submitted to Biomaterials, a section of the journal Frontiers in Bioengineering and Biotechnology

Article

Publisher ID: 866208

DOI: 10.3389/fbioe.2022.866208

PMC ID: 9011111

PubMed ID: 35433664

SO-VID: a96f1472-1191-4442-b072-f3bc9347148d

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Exosome-Laden Hydrogels: A Novel Cell-free Strategy for In-situ Bone Tissue Regeneration

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Karger: Coronavirus / COVID-19

Most cited references 111

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

Regulation of immune responses by extracellular vesicles.

Progress in Exosome Isolation Techniques

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