Bionic biligand single chain nanogel Regulating Stem cell behavior and differentiation

In the organism, the fate of cell behavior and surface receptors with extracellular matrix cells with a bioactive ligand interactions have very close contact. Identifying a ligand such cells can induce cell adhesion, regulation of cell further dynamic perception of signals in the extracellular matrix. Extracellular matrices most widely used for adjusting the RGD peptide ligand cell adhesion behavior, can be dynamically combined with integrins on the cell membrane, activation of intracellular pathways classical cell, achieve the regulation of cell behavior and differentiation. Further, TF Prof. side and have been reported recently discovered A novel short peptide Foxy5, can simulate Wnt5a enhance human mesenchymal stem cells into osteoblasts (Li et al., .. Science Advances 2019; 5: eaaw3896). Through careful study, we have demonstrated that human bone marrow can be enhanced Foxy5 in mesenchymal stem cells by non-classical mechanics cell transduction pathways and to induce osteogenic differentiation. In this study, the two kinds of modification of the same regulatory ligands bionic single chain nano paste by a conformational change in the dynamic regulation of a single-stranded nano paste, further evidence of non-activation of the classical pathway can be further reacted with cells conventional activated cellular pathways combined achieved in human bone marrow mesenchymal stem cell differentiation and the dynamic behavior and coordinately regulated. This material biomimetic design method based on single-stranded nanogels, the future expected to be applied more different ligand system to study the behavior of the cells under the action more ligands. The study recently Biomimetic Presentation of Ligands via Cryptic Single-Chain Nanogels for Synergistic Regulation of Stem Cells was published in ACS Nano (https://doi.org/10.1021/ acsnano.9b08564). .

1 biomimetic single chain Nanogel design and preparation:

First, the researchers based on pre-controllable reversible addition – fragmentation chain transfer polymerization (RFAT) and the mechanism of the process, single-chain successfully nanogels having two biological ligand was prepared. And by copolymerizing a reactive ligand in a folded single strand gel implementation hiding its temporary. This ligand can be hidden by an external stimulus selectively expressed at a particular time, so as to realize multi-ligand synergistically with the regulation of stem cell behavior and differentiation.

仿生双配体单链高分子纳米凝胶协同调控干细胞行为与分化
FIG. I. Design and fabrication of a single-stranded Nanogel ligand having a double structure of a biomimetic

2. Bionic single-stranded stem cells Nanogel regulation and differentiation behavior: single chain nanostructures

having hidden ligand structure ensures double ligand limited to a short distance variation can be more accurately and efficiently applied to a single recipient cell. In order to study a variety of ligands and the expression of stem cell regulation efficiency, researchers first cells were cultured in a modified single strand glass plate bionic Nanogel, stimulates a material bis ligand coordinately expressed at a particular time, by observing the expression of stem cell morphology and differentiation, bionic confirmed by single strand nanogel multi-ligand synergistically efficient regulation and differentiation of stem cell lines.

仿生双配体单链高分子纳米凝胶协同调控干细胞行为与分化
Figure 2. bionic single chain Nanogel efficient coordination of the behavior of stem cells and differentiation regulation

This study reported kinematic chain Nanogel unfolded natural cells preliminary simulation of multi-stage stimulation of extracellular matrix structure for the study of cell-extracellular matrix interaction mechanism provides a more flexible platform. The platform is expected to be applied to future research on the regulation of more multi-ligand cancer cells, immune cells express a more favorable sophisticated tool for biomedical research and cell signal mechanism and application of workers. The study by the Chinese University of Hong Kong, Swiss Federal Institute of Materials Science and Technology, University of Manchester, Sun Yat-sen collaboration. Chinese University of Hong Kong PhD Chen Xiao Yu , Li Jin Qian , and the Swiss Institute for Materials Science and Technology Chang Wei-hole researcher as a co-first author of the paper. University of Manchester Professor LI Jiashen and Sun Yat-sen handsome XT professor as the co-author of the paper, Chinese University [12 Hong Kong3] the professor Dawn corresponding author for the paper. Recent related academic side Prof.: 1 Li, R; et al .; * Bian, L. Synthetic presentation of noncanonical Wnt5a motif promotes mechanosensing-dependent differentiation of stem cells and regeneration Science Advances, 2019,.. . 5: eaaw3896.2 Zhou, H .; Liang, C .; Wei, Z .; Bai, Y .; Bhaduri, SB; Webster, TJ; * Bian, L .; * Yang, L. Injectable biomaterials for translational medicine . Materials Today, in press.3. Chen, X .; et al .; * Bian, L. Conformational manipulation of scale-up prepared single chain polymeric nanogels for multiscale regulation of cells. Nature Communications, 2019, volume 10, Article number .: 2075.4 + Feng, Q .; + Xu, J .; et al .; * Qin, L; * Bian, L. Dynamic and cell-infiltratable hydrogels as injectable carrier of therapeutic cells and drugs for treating challengi.. Ng bone defects ACS Central Science, 2019, 5 (3), pp 440-450.5 + Kang, H .; + Wong, SHD; et al .; Li, G .; * Bian, L. Anisotropic ligand nanogeometry modulates the adhesion and polarization state of macrophages Nano Letters, 2019 Mar 13; 19 (3):. 1963-1975.6 + Wong, SHD; + Yin, B .; et al .; Li, G .; * Choi, CH; * Bian. , L. Anisotropic nanoscale presentation of cell adhesion ligand enhances the recruitment of diverse integrins in adhesion structures and mechanosensing-dependent differentiation of stem cells. Advanced Functional Materials, Volume 29, Issue 8, 2019, adfm.201806822.7. + Kang, H .; + Yang, B .; et al .; Li, G .; * Bian, L. Immunoregulation of macrophages by dynamic presentation via ligand ligand-cation coordination Nature Communications, 2019, volume 10, Article number:. 1696.8. + Kang, H .; + Zhang, K .; et al .; Dravid, V .; * Bian, L. In situ reversible heterodimeric nanoswitch controlled by metal ion-ligand coordination regulates the adhesion, release, and differentiation of stem . cells Advanced Materials, 2018 Nov;. 30 (44), adma.201803591.9 + Zhang, K .; + Yuan, W .; et al .; * Zhang, Z .; * Bian, L. Highly dynamic nanocomposite hydrogels self- assembled by metal ion-ligand coordination, Small, 2019, smll.201900242.10. + Zhang, K .; + Jia, Z .; et al .; * Wang, D .; * Bian, L. Adaptable hydrogels mediate cofactor-assisted activation . of biomarker-responsive drug delivery via positive feedback for enhanced tissue regeneration Advanced Science, 2018 Dec; 5 (12): 1800875.

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