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      Cell-free exosome-laden scaffolds for tissue repair

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          Abstract

          Exosome seeded on the designed scaffold can achieve local and sustained-release for efficient tissue repair.

          Abstract

          With the development of regenerative medicine, tissue repair at the molecular, cellular, tissue, and organ level has seen continuous improvements over traditional techniques. As the core of tissue repair, seed cells are widely used in various fields of regenerative medicine. However, their use is still associated with problems such as decreased cell survival and regeneration capacity after transplantation, immune rejection, and ethical concerns. Therefore, it is difficult to universally and safely apply stem cell banks for regenerative medicine. The paracrine effects of cells, especially secretion of exosomes, play vital roles in cell communication, immune response, angiogenesis, scar formation, tissue repair, and other biological functions. Exosomes are a type of nanoscale extracellular vesicle that contain biologically active molecules such as RNA and proteins; therefore, exosomes can replicate the functions of their parental cells. Meanwhile, exosomes can be used as nanocarriers to deliver active factors or small molecules to promote tissue repair. Preclinical studies of exosomes in tissue engineering and regenerative medicine have been carried in the fields of bone/cartilage repair, nerve regeneration, liver and kidney regeneration, skin repair, vascular tissue regeneration, etc. This review introduces exosomes from the aspects of biogenesis, composition, identification, and isolation, and focuses on the development status of scaffold materials for exosome delivery. In addition, we highlight examples of exosome-laden scaffolds for preclinical applications in tissue repair. We look forward to the broad application prospects of exosome-laden scaffolds.

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          Most cited references81

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          Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

          ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
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            Shedding light on the cell biology of extracellular vesicles

            Extracellular vesicles are a heterogeneous group of cell-derived membranous structures comprising exosomes and microvesicles, which originate from the endosomal system or which are shed from the plasma membrane, respectively. They are present in biological fluids and are involved in multiple physiological and pathological processes. Extracellular vesicles are now considered as an additional mechanism for intercellular communication, allowing cells to exchange proteins, lipids and genetic material. Knowledge of the cellular processes that govern extracellular vesicle biology is essential to shed light on the physiological and pathological functions of these vesicles as well as on clinical applications involving their use and/or analysis. However, in this expanding field, much remains unknown regarding the origin, biogenesis, secretion, targeting and fate of these vesicles.
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              Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication

              The ability of exosomes to transfer cargo from donor to acceptor cells, thereby triggering phenotypic changes in the latter, has generated substantial interest in the scientific community. However, the extent to which exosomes differ from other extracellular vesicles in terms of their biogenesis and functions remains ill-defined. Here, we discuss the current knowledge on the specificities of exosomes and other types of extracellular vesicles, and their roles as important agents of cell-to-cell communication.
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                Author and article information

                Contributors
                Journal
                NANOHL
                Nanoscale
                Nanoscale
                Royal Society of Chemistry (RSC)
                2040-3364
                2040-3372
                May 20 2021
                2021
                : 13
                : 19
                : 8740-8750
                Affiliations
                [1 ]Department of Orthopedics
                [2 ]Shenzhen Second People's Hospital (First Affiliated Hospital of Shenzhen University
                [3 ]Health Science Center)
                [4 ]Shenzhen 518035
                [5 ]China
                [6 ]Tsinghua University Shenzhen International Graduate School
                [7 ]Innovation Leading Engineering Doctor
                [8 ]Class 9 of 2020
                [9 ]Shenzhen
                [10 ]Institute of Biomedicine and Health Engineering
                [11 ]Department of Child and Adolescent Psychiatry
                [12 ]Shenzhen Kangning Hospital
                [13 ]Shenzhen Mental Health Center
                [14 ]Shenzhen Key Laboratory for Psychological Healthcare & Shenzhen Institute of Mental Health
                Article
                10.1039/D1NR01314A
                33969373
                02c483c0-8a63-4d0c-a277-b6ba7cea422d
                © 2021

                http://creativecommons.org/licenses/by/3.0/

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