Korea University: A Giant Step to the Commercialization of ‘Up-and-Down’ Customized Regeneration Therapy
A research group in the Department of Materials Science and Engineering developed the world’s first ligand screen system that is capable of remotely controlling the adhesion and differentiation of stem cells on a biomaterial surface.
The results obtained by Professor Kang Hee-min’s group (first author: Hong Hyun-sik, a student in the Master’s and & Doctoral Degree Combined Program) were published in Advanced Materials (Impact Factor: 30.849), a globally acclaimed journal, on October 16, 2021. *Title: Dynamic Ligand Screening by Magnetic Nanoassembly Modulates Stem Cell Differentiation
A stem cell is an undifferentiated cell that can sense the surrounding environment and differentiate into a specific tissue cell corresponding to that environment. Due to their characteristics, stem cells can be induced to differentiate into the tissue cells of various organs, including muscles, cardiac muscles, blood vessels, bones and cartilage. Thus, they are drawing much attention in regenerative medicine and engineering. However, their commercialization is challenging because controlling the adhesion and differentiation of stem cells under in vivo conditions is difficult.
*Stem cell: An undifferentiated cell that can differentiate into particular tissue cells depending on the surrounding environment. Stem cells are drawing much attention as the essential cell type for patient-customized treatments, including cell therapy, tissue regeneration, and artificial organs.
The research group prepared assemblies consisting of superparamagnetic magnetite (Fe3O4) nanoparticles, and attached them via elastic linkers to a material surface on which RGD ligands are distributed, to fabricate a ligand screen. The nanogaps between the screen and the ligands can be adjusted above the material surface through the motion of the magnetic assembly (screen) using an external magnetic field, and in this way the behavior of the stem cell can be remotely controlled.
*Superparamagnetism: A magnetic property of small magnetic materials, such as nanoparticles. Materials having superparamagnetism are magnetized when a magnetic field is applied and demagnetized when the magnetic field is removed.
*Magnetite assembly (screen): An assembly of superparamagnetic magnetite particles about 10 nm in size. When a magnetic field is applied, the assembly is magnetized and so moves toward the magnet, and, when the magnetic field is removed, the assembly is demagnetized, thereby allowing for remote and dynamic real-time control.
*Elastic linker: The linkers, polyethylene glycol molecules tens of nanometers in length, connect and fix the screen to the material surface. When a magnetic field is applied, the screen is allowed to move just as far as the length of the linker.
*RGD ligand: An amino acid sequence for mediating cell adhesion found in the proteins of the extracellular matrix, such as fibronectin, laminin or collagen. Receptors (integrins) on cell membranes recognize the RGD ligands and then allow the cells to adhere.
The research group showed that the adhesion and osteogenic differentiation of stem cells are enhanced when the nanogaps between the screen and the ligands are increased by an external magnetic field and inhibited when the nanogaps are decreased. Moreover, the research group also determined how the stem cell controlling effect depended upon the size of the assembly (screen), and showed that stem cell adhesion and mechanosensing are enhanced at low distributions of exposed ligands. Furthermore, they showed that the effect also exists in vivo.
The system developed in this study allows control of the size and shape of the ligand screen, and the RGD ligands can be replaced by varied biocompatible proteins to customize the treatments applied to individual patients. The system presents a new paradigm of tissue regeneration treatment, because in vivo reactions can be remotely and harmlessly controlled by applying an external magnetic field to adjust the nanogaps between the screen and ligands.