Immunomodulatory Scaffolds Derived from Lymph Node Extracellular Matrices.

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.

Organoid engineering with microfluidics and biomaterials for liver, lung disease, and cancer modeling.

As life expectancy improves and the number of people suffering from various diseases increases, the need for developing effective personalized disease models is rapidly rising. The development of organoid technology has led to better recapitulation of the in vivo environment of organs, and can overcome the constraints of existing disease models. However, for more precise disease modeling, engineering approaches such as microfluidics and biomaterials, that aid in mimicking human physiology, need to be integrated with the organoid models. In this review, we introduce key elements for disease modeling and recent engineering advances using both liver and lung organoids. Due to the importance of personalized medicine, we also emphasize patient-derived cancer organoid models and their engineering approaches. These organoid-based disease models combined with microfluidics, biomaterials, and co-culture systems will provide a powerful research platform for understanding disease mechanisms and developing precision medicine; enabling preclinical drug screening and drug development. STATEMENT OF SIGNIFICANCE: The development of organoid technology has led to better recapitulation of the in vivo environment of organs, and can overcome the constraints of existing disease models. However, for more precise disease modeling, engineering approaches such as microfluidics and biomaterials, that aid in mimicking human physiology, need to be integrated with the organoid models. In this review, we introduce liver, lung, and cancer organoids integrated with various engineering approaches as a novel platform for personalized disease modeling. These engineered organoid-based disease models will provide a powerful research platform for understanding disease mechanisms and developing precision medicine.