Immunomodulatory Scaffolds Derived from Lymph Node Extracellular Matrices

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

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)14037-14049
Number of pages13
JournalACS Applied Materials and Interfaces
Volume13
Issue number12
DOIs
Publication statusPublished - 2021 Mar 31

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All Science Journal Classification (ASJC) codes

  • General Materials Science

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