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Immunomodulatory Scaffolds Derived from Lymph Node Extracellular Matrices

Authors
 Yi Sun Choi  ;  Eunseon Jeong  ;  Jung Seung Lee  ;  Su Kyeom Kim  ;  Sung-Hyun Jo  ;  Yun-Gon Kim  ;  Hak-Joon Sung  ;  Seung-Woo Cho  ;  Yoonhee Jin 
Citation
 ACS APPLIED MATERIALS & INTERFACES, Vol.13(12) : 14037-14049, 2021-03 
Journal Title
ACS APPLIED MATERIALS & INTERFACES
ISSN
 1944-8244 
Issue Date
2021-03
Keywords
3D hydrogel ; decellularized matrix ; immunomodulation ; lymph node extracellular matrix ; macrophage polarization ; muscle regeneration
Abstract
Immunomodulation in the local tissue microenvironment is pivotal for the determination of macrophage phenotypes and regulation of functions necessary for pro-healing effects. Herein, we demonstrate that a lymph node extracellular matrix (LNEM) prepared by the decellularization of lymph node tissues can mimic lymph node microenvironments for immunomodulation in two-dimensional (2D) and three-dimensional (3D) formats. The LNEM exhibits strengthened immunomodulatory effects in comparison to conventional collagen-based platforms. A 3D LNEM hydrogel is more effective than the 2D LNEM coating in inducing M2 macrophage polarization. The 3D LNEM induces macrophage elongation and enhances the M2-type marker expression and the secretion of anti-inflammatory cytokines. Additionally, the phagocytic function of macrophages is improved upon exposure to the intricate 3D LNEM environment. We demonstrate the reduced susceptibility of liver organoids to a hepatotoxic drug when co-cultured with macrophages in a 3D LNEM. This effect could be attributed to the enhanced anti-inflammatory functions and indicates its potential as a drug-testing platform that enables drug responses similar to those observed in vivo. Finally, the implantation of an LNEM hydrogel in a mouse volumetric muscle loss model facilitates the recruitment of host macrophages to the site of injury and enhances macrophage polarization toward the M2 phenotype for tissue healing in vivo. Therefore, 3D immune system-mimicking biomaterials could serve as useful platforms for tissue modeling and regenerative medicine development.
Full Text
https://pubs.acs.org/doi/10.1021/acsami.1c02542
DOI
10.1021/acsami.1c02542
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
Yonsei Authors
Sung, Hak-Joon(성학준) ORCID logo https://orcid.org/0000-0003-2312-2484
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/184107
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