Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway
Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and...
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MDPI AG
2025-08-01
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| author | Weijian Hu Xin Xie Jiabin Xu |
| author_facet | Weijian Hu Xin Xie Jiabin Xu |
| author_sort | Weijian Hu |
| collection | DOAJ |
| description | Healing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine. |
| format | Article |
| id | doaj-art-d2d1a21087944d829e3d922b1044698e |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-d2d1a21087944d829e3d922b1044698e2025-08-20T03:35:58ZengMDPI AGCells2073-44092025-08-011415121410.3390/cells14151214Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt PathwayWeijian Hu0Xin Xie1Jiabin Xu2Medical College, Northwest University, Xi’an 710000, ChinaCollege of Life Sciences, Northwest University, Xi’an 710000, ChinaSchool of Stomatology, Xuzhou Medical University, Xuzhou 221004, ChinaHealing large bone defects remains challenging. Gelatin scaffolds are biocompatible and biodegradable, but lack osteoinductive activity. Plant-derived exosomes carry miRNAs, growth factors, and proteins that modulate osteogenesis, but free exosomes suffer from poor stability, limited targeting, and low bioavailability in vivo. We developed a 3D GelMA hydrogel loaded with Epimedium-derived exosomes (“GelMA@Exo”) to improve exosome retention, stability, and sustained release. Its effects on MC3T3-E1 preosteoblasts—including proliferation, osteogenic differentiation, migration, and senescence—were evaluated via in vitro assays. Angiogenic potential was assessed using HUVECs. Underlying mechanisms were examined at transcriptomic and protein levels to elucidate GelMA@Exo’s therapeutic osteogenesis actions. GelMA@Exo exhibited sustained exosome release, enhancing exosome retention and cellular uptake. In vitro, GelMA@Exo markedly boosted MC3T3-E1 proliferation, migration, and mineralized nodule formation, while reducing senescence markers and promoting angiogenesis in HUVECs. Mechanistically, GelMA@Exo upregulated key osteogenic markers (RUNX2, TGF-β1, Osterix, COL1A1, ALPL) and activated the PI3K/Akt pathway. Transcriptomic data confirmed global upregulation of osteogenesis-related genes and bone-regeneration pathways. This study presents a GelMA hydrogel functionalized with plant-derived exosomes, which synergistically provides osteoinductive stimuli and structural support. The GelMA@Exo platform offers a versatile strategy for localized delivery of natural bioactive molecules and a promising approach for bone tissue engineering. Our findings provide strong experimental evidence for the translational potential of plant-derived exosomes in regenerative medicine.https://www.mdpi.com/2073-4409/14/15/1214gelatin methacryloylepimedium-derived exosomesosteogenic differentiationPI3K/Akt signaling pathwayanti-senescenceangiogenesis |
| spellingShingle | Weijian Hu Xin Xie Jiabin Xu Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway Cells gelatin methacryloyl epimedium-derived exosomes osteogenic differentiation PI3K/Akt signaling pathway anti-senescence angiogenesis |
| title | Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway |
| title_full | Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway |
| title_fullStr | Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway |
| title_full_unstemmed | Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway |
| title_short | Epimedium-Derived Exosome-Loaded GelMA Hydrogel Enhances MC3T3-E1 Osteogenesis via PI3K/Akt Pathway |
| title_sort | epimedium derived exosome loaded gelma hydrogel enhances mc3t3 e1 osteogenesis via pi3k akt pathway |
| topic | gelatin methacryloyl epimedium-derived exosomes osteogenic differentiation PI3K/Akt signaling pathway anti-senescence angiogenesis |
| url | https://www.mdpi.com/2073-4409/14/15/1214 |
| work_keys_str_mv | AT weijianhu epimediumderivedexosomeloadedgelmahydrogelenhancesmc3t3e1osteogenesisviapi3kaktpathway AT xinxie epimediumderivedexosomeloadedgelmahydrogelenhancesmc3t3e1osteogenesisviapi3kaktpathway AT jiabinxu epimediumderivedexosomeloadedgelmahydrogelenhancesmc3t3e1osteogenesisviapi3kaktpathway |