Sayan Deb Dutta (강원대학교) | 한빛사논문 > 한빛사

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Bioact. Mater., 2024 Nov 27:45:345-362 | https://doi.org/10.1016/j.bioactmat.2024.11.026 3D bioprinting of engineered exosomes secreted from M2-polarized macrophages through immunomodulatory biomaterial promotes in vivo wound healing and angiogenesis

Sayan Deb Dutta ^a,b,c,1, Jeong Man An^d,1, Jin Hexiu ^e,1, Aayushi Randhawa ^a,f,1, Keya Ganguly ^a, Tejal V. Patil ^a,f, Thavasyappan Thambi ^g, Jangho Kim^h, Yong-kyu Leeⁱ, Ki-Taek Lim^a,b,f

^aDepartment of Biosystems Engineering, Kangwon National University, 24341, Chuncheon, Republic of Korea
^bInstitute of Forest Science, Kangwon National University, 24341, Chuncheon, Republic of Korea
^cSchool of Medicine, University of California Davis, 95817, Sacramento, United States
^dDepartment of Bioengineering, College of Engineering, Hanyang University, 04763, Seoul, Republic of Korea
^eDepartment of Plastic and Traumatic Surgery, Capital Medical University, 100069, Beijing, China
^fInterdisciplinary Program in Smart Agriculture, Kangwon National University, 24341, Chuncheon, Republic of Korea
^gGraduate School of Biotechnology, College of Life Sciences, Kyung Hee University, 17104, Yongin, Republic of Korea
^hDepartment of Convergence Biosystems Engineering, Chonnam National University, 61186, Gwangju, Republic of Korea
ⁱDepartment of Chemical and Biological Engineering, Korea National University of Transportation, 27470, Chungju, Republic of Korea

¹These four authors have contributed equally to this manuscript.
Corresponding authors: Jangho Kim, Yong-kyu Lee, Ki-Taek Lim

Abstract

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.

논문정보

형식Research article
게재일2024년 11월 (BRIC 등록일 2024-12-16)
연구진국내(교신)+국외 연구진
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