Mesenchymal stromal cell secretome in scaffold-based drug delivery: Advances, applications, and future directions

Sep 27, 2025International journal of biological macromolecules

Using support cell secretions with scaffolds to deliver drugs: progress, uses, and future possibilities

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Regenerative Health on OpenScience ↗PubMed ↗DOI ↗

Abstract

The mesenchymal stromal cell (MSC) secretome may enhance tissue regeneration through paracrine signaling.

The MSC secretome includes growth factors, cytokines, chemokines, and extracellular vesicles.
Integrating the secretome with biomaterial scaffolds could improve drug delivery and tissue repair.
Scaffold systems such as hydrogels and 3D-printed constructs enable controlled release of the secretome.
MSC-derived exosomes act as efficient carriers, enhancing bioavailability and protecting therapeutic cargo.
Preclinical studies indicate efficacy in applications like wound healing and cartilage repair.
Challenges remain in production standardization and regulatory constraints that may impact clinical use.

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The mesenchymal stromal cell (MSCs) secretome, comprising growth factors, cytokines, chemokines, and extracellular vesicles (exosomes), has emerged as a promising cell-free therapeutic approach in regenerative medicine. This review highlights recent advancements in integrating the MSC secretome with biomaterial scaffolds for drug delivery and tissue repair. The secretome's paracrine signaling promotes tissue regeneration, offering advantages over traditional cell-based therapies by reducing immune risks and enhancing scalability. Scaffold systems such as hydrogels, electrospun nanofibers, and 3D-printed constructs have been designed to encapsulate the MSC secretome or exosomes, enabling controlled and localized delivery. Loading strategies, including surface adsorption, hydrogel embedding, microsphere encapsulation, and lyophilization, are employed to optimise release kinetics. MSC-derived exosomes, in particular, serve as efficient nanoscale carriers, enhancing bioavailability and protecting therapeutic cargo. Preclinical studies demonstrate the efficacy of secretome-integrated scaffolds in wound healing, cartilage repair, angiogenesis, antifibrotic therapy, neuroprotection, and tumour targeting. While the approach shows strong therapeutic promise, challenges such as production standardization, batch variability, targeting specificity, and regulatory constraints remain. Ongoing research in scaffold engineering and secretome optimization is essential to overcome these barriers and support clinical translation. Overall, MSC secretome-integrated scaffolds represent a safe, effective, and scalable strategy for regenerative therapy.

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Mesenchymal stromal cell secretome in scaffold-based drug delivery: Advances, applications, and future directions

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