1. Immunomodulatory Scaffolds Derived from Lymph Node Extracellular Matrices
- Author
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Jung Seung Lee, Su Kyeom Kim, Yoonhee Jin, Yi Sun Choi, Hak-Joon Sung, Eunseon Jeong, Yun-Gon Kim, Sung-Hyun Jo, and Seung Woo Cho
- Subjects
Materials science ,Swine ,Macrophage polarization ,Biocompatible Materials ,02 engineering and technology ,Immunomodulation ,Extracellular matrix ,03 medical and health sciences ,In vivo ,Extracellular ,medicine ,Animals ,Macrophage ,General Materials Science ,Lymph node ,030304 developmental biology ,0303 health sciences ,Decellularization ,Tissue Scaffolds ,Macrophages ,Macrophage Activation ,021001 nanoscience & nanotechnology ,M2 Macrophage ,Extracellular Matrix ,Cell biology ,medicine.anatomical_structure ,Lymph Nodes ,0210 nano-technology - 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.
- Published
- 2021
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