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Intensive studies on stem cell therapy reveal that benefits of stem cells attribute to the paracrine effects. Hence, direct delivery of stem cell secretome to the injured site shows the comparative therapeutic efficacy of living cells while avoiding the potential limitations. However, conventional systemic administration of stem cell secretome often leads to rapid clearance in vivo. Therefore, a variety of different biomaterials are developed for sustained and controllable delivery of stem cell secretome to improve therapeutic efficiency. In this review, we first introduce current approaches for the preparation and characterization of stem cell secretome as well as strategies to improve their therapeutic efficacy and production. The up-to-date delivery platforms are also summarized, including nanoparticles, injectable hydrogels, microneedles, and scaffold patches. Meanwhile, we discuss the underlying therapeutic mechanism of stem cell secretome for the treatment of various diseases. In the end, future opportunities and challenges are proposed.

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