2025-07-25 カリフォルニア大学バークレー校 (UCB)
<関連情報>
- https://www.engineering.columbia.edu/about/news/columbia-engineering-researchers-turn-dairy-byproduct-tissue-repair-gel
- https://www.cell.com/matter/abstract/S2590-2385(25)00383-2
バイオアクティブな注入可能ハイドロゲルにおける細胞外小胞の動的交連剤としての役割 Extracellular vesicles as dynamic crosslinkers for bioactive injectable hydrogels
Artemis Margaronis ∙ Caterina Piunti ∙ Ryan R. Hosn ∙ … ∙ Kam Leong ∙ Elisa Cimetta ∙ Santiago Correa
Matter Published:July 25, 2025
DOI:https://doi.org/10.1016/j.matt.2025.102340
Graphical abstract
Progress and potential
Harnessing the therapeutic potential of extracellular vesicles (EVs) is an area of growing interest in biomaterials research. Although EVs are potent mediators of intercellular communication, their integration into engineered materials has been hindered by scalability challenges, premature release, and formulation complexity. To address these barriers, we leveraged EVs derived from yogurt whey—an abundant, low-cost alternative to cell-culture sources—to enable high-throughput investigation of gelation behavior. This allowed us to systematically define the polymer properties, including alkyl-chain length and degree of hydrophobic modification, required for EV-mediated hydrogel formation. We also found that EVs act not only as a supramolecular crosslinker but, in certain contexts, as a crowding agent that reinforces network structure. This tunable framework is compatible with vesicles from microbial and mammalian sources.
Beyond serving as a scalable model system, yogurt-derived EVs exhibited intrinsic bioactivity in vivo. EV hydrogels formed with these vesicles were biocompatible, promoted spontaneous angiogenesis within 1 week, and recruited a distinct immune niche enriched in myeloid cells and regulatory T cells—features not observed with synthetic liposomal controls. These results highlight the potential of agricultural EVs as both a research tool and a functional component of regenerative biomaterials. Together, this work provides a design framework for researchers in both the EV and biomaterials communities, offering clear formulation principles to support the development of robust, scalable, and bioactive EV-based materials.
Highlights
- EVs require optimally modified polymers to form injectable hydrogels
- EVs in hydrogels structurally act as crosslinkers and macromolecular crowders
- Design framework extends to hydrogels formed with microbial and mammalian EVs
- In vivo, yogurt EV hydrogels promote vascularization and immune-cell infiltration
Summary
Hydrogels are multifunctional biomaterials but are often composed of synthetic building blocks that do not inherently present biological signals to cells. Extracellular vesicles (EVs) offer unique bioactivity, but stably incorporating them into hydrogels remains a challenge. Here, we define the design principles for supramolecular hydrogels crosslinked by EVs. Bovine-derived yogurt EVs are used as a scalable source of bioactive EVs for systematic hydrogel development. Mixing EVs with optimally modified cellulose-based polymers yields injectable hydrogels with tunable mechanical properties. Following optimization with yogurt EVs, this platform’s versatility is demonstrated by formulating hydrogels with artificial microbial and mammalian nanovesicles. In vivo studies show EV hydrogel biocompatibility, intrinsic angiogenic activity, and emergence of an immune niche with broad immune-cell engagement, highlighting their potential in regenerative medicine. These findings establish a framework for designing EV-crosslinked supramolecular hydrogels that integrate the natural bioactivity of EVs with the biomedical potential of injectable hydrogel technology.
