3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis
Biomaterial composition and surface charge play a critical role in macrophage polarization, providing a molecular cue for immunomodulation and tissue regeneration. In this study, we developed bifunctional hydrogel inks for accelerating M2 macrophage polarization and exosome (Exo) cultivation for wou...
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KeAi Communications Co., Ltd.
2025-03-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X24005176 |
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| author | Sayan Deb Dutta Jeong Man An Jin Hexiu Aayushi Randhawa Keya Ganguly Tejal V. Patil Thavasyappan Thambi Jangho Kim Yong-kyu Lee Ki-Taek Lim |
| author_facet | Sayan Deb Dutta Jeong Man An Jin Hexiu Aayushi Randhawa Keya Ganguly Tejal V. Patil Thavasyappan Thambi Jangho Kim Yong-kyu Lee Ki-Taek Lim |
| author_sort | Sayan Deb Dutta |
| collection | DOAJ |
| description | Biomaterial composition and surface charge play a critical role in macrophage polarization, providing a molecular cue for immunomodulation and tissue regeneration. In this study, we developed bifunctional hydrogel inks for accelerating M2 macrophage polarization and exosome (Exo) cultivation for wound healing applications. For this, we first fabricated polyamine-modified three-dimensional (3D) printable hydrogels consisting of alginate/gelatin/polydopamine nanospheres (AG/NSPs) to boost M2-exosome (M2-Exo) secretion. The cultivated M2-Exo were finally encapsulated into a biocompatible collagen/decellularized extracellular matrix (COL@d-ECM) bioink for studying angiogenesis and in vivo wound healing study. Our findings show that 3D-printed AGP hydrogel promoted M2 macrophage polarization by Janus kinase/signal transducer of activation (JAK/STAT), peroxisome proliferator-activated receptor (PPAR) signaling pathways and facilitated the M2-Exo secretion. Moreover, the COL@d-ECM/M2-Exo was found to be biocompatible with skin cells. Transcriptomic (RNA-Seq) and real-time PCR (qRT-PCR) study revealed that co-culture of fibroblast/keratinocyte/stem cells/endothelial cells in a 3D bioprinted COL@d-ECM/M2-Exo hydrogel upregulated the skin-associated signature biomarkers through various regulatory pathways during epidermis remodeling and downregulated the mitogen-activated protein kinase (MAPK) signaling pathway after 7 days. In a subcutaneous wound model, the 3D bioprinted COL@d-ECM/M2-Exo hydrogel displayed robust wound remodeling and hair follicle (HF) induction while reducing canonical pro-inflammatory activation after 14 days, presenting a viable therapeutic strategy for skin-related disorders. |
| format | Article |
| id | doaj-art-6ba20f9675bb4f1ab4d4e60f6b73ea43 |
| institution | Kabale University |
| issn | 2452-199X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj-art-6ba20f9675bb4f1ab4d4e60f6b73ea432025-01-26T05:04:24ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-03-01453453623D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesisSayan Deb Dutta0Jeong Man An1Jin Hexiu2Aayushi Randhawa3Keya Ganguly4Tejal V. Patil5Thavasyappan Thambi6Jangho Kim7Yong-kyu Lee8Ki-Taek Lim9Department of Biosystems Engineering, Kangwon National University, 24341, Chuncheon, Republic of Korea; Institute of Forest Science, Kangwon National University, 24341, Chuncheon, Republic of Korea; School of Medicine, University of California Davis, 95817, Sacramento, United StatesDepartment of Bioengineering, College of Engineering, Hanyang University, 04763, Seoul, Republic of KoreaDepartment of Plastic and Traumatic Surgery, Capital Medical University, 100069, Beijing, ChinaDepartment of Biosystems Engineering, Kangwon National University, 24341, Chuncheon, Republic of Korea; Interdisciplinary Program in Smart Agriculture, Kangwon National University, 24341, Chuncheon, Republic of KoreaDepartment of Biosystems Engineering, Kangwon National University, 24341, Chuncheon, Republic of KoreaDepartment of Biosystems Engineering, Kangwon National University, 24341, Chuncheon, Republic of Korea; Interdisciplinary Program in Smart Agriculture, Kangwon National University, 24341, Chuncheon, Republic of KoreaGraduate School of Biotechnology, College of Life Sciences, Kyung Hee University, 17104, Yongin, Republic of KoreaDepartment of Convergence Biosystems Engineering, Chonnam National University, 61186, Gwangju, Republic of Korea; Corresponding author.Department of Chemical and Biological Engineering, Korea National University of Transportation, 27470, Chungju, Republic of Korea; Corresponding author.Department of Biosystems Engineering, Kangwon National University, 24341, Chuncheon, Republic of Korea; Institute of Forest Science, Kangwon National University, 24341, Chuncheon, Republic of Korea; Interdisciplinary Program in Smart Agriculture, Kangwon National University, 24341, Chuncheon, Republic of Korea; Corresponding author. Department of Biosystems Engineering, Kangwon National University, 24341, Chuncheon, Republic of Korea.Biomaterial composition and surface charge play a critical role in macrophage polarization, providing a molecular cue for immunomodulation and tissue regeneration. In this study, we developed bifunctional hydrogel inks for accelerating M2 macrophage polarization and exosome (Exo) cultivation for wound healing applications. For this, we first fabricated polyamine-modified three-dimensional (3D) printable hydrogels consisting of alginate/gelatin/polydopamine nanospheres (AG/NSPs) to boost M2-exosome (M2-Exo) secretion. The cultivated M2-Exo were finally encapsulated into a biocompatible collagen/decellularized extracellular matrix (COL@d-ECM) bioink for studying angiogenesis and in vivo wound healing study. Our findings show that 3D-printed AGP hydrogel promoted M2 macrophage polarization by Janus kinase/signal transducer of activation (JAK/STAT), peroxisome proliferator-activated receptor (PPAR) signaling pathways and facilitated the M2-Exo secretion. Moreover, the COL@d-ECM/M2-Exo was found to be biocompatible with skin cells. Transcriptomic (RNA-Seq) and real-time PCR (qRT-PCR) study revealed that co-culture of fibroblast/keratinocyte/stem cells/endothelial cells in a 3D bioprinted COL@d-ECM/M2-Exo hydrogel upregulated the skin-associated signature biomarkers through various regulatory pathways during epidermis remodeling and downregulated the mitogen-activated protein kinase (MAPK) signaling pathway after 7 days. In a subcutaneous wound model, the 3D bioprinted COL@d-ECM/M2-Exo hydrogel displayed robust wound remodeling and hair follicle (HF) induction while reducing canonical pro-inflammatory activation after 14 days, presenting a viable therapeutic strategy for skin-related disorders.http://www.sciencedirect.com/science/article/pii/S2452199X24005176ExosomeImmunomodulationDecellularized extracellular matrixSkin bioprintingAngiogenesisWound healing |
| spellingShingle | Sayan Deb Dutta Jeong Man An Jin Hexiu Aayushi Randhawa Keya Ganguly Tejal V. Patil Thavasyappan Thambi Jangho Kim Yong-kyu Lee Ki-Taek Lim 3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis Bioactive Materials Exosome Immunomodulation Decellularized extracellular matrix Skin bioprinting Angiogenesis Wound healing |
| title | 3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis |
| title_full | 3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis |
| title_fullStr | 3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis |
| title_full_unstemmed | 3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis |
| title_short | 3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis |
| title_sort | 3d bioprinting of engineered exosomes secreted from m2 polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis |
| topic | Exosome Immunomodulation Decellularized extracellular matrix Skin bioprinting Angiogenesis Wound healing |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X24005176 |
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