Mechanical Characterization of Human Brain Tissue and SoftDynamic Gels Exhibiting Electromechanical Neuro-Mimicry

Synthetic hydrogels are an important class of materialsin tissue engineering, drug delivery, and other biomedicalfields. Their mechanical and electrical properties can betuned to match those of biological tissues. In this work,we report on hydrogels that exhibit both mechanical andelectrical biomimicry. The presented dual networks consistof supramolecular networks formed from 2:1 homoternarycomplexes of imidazolium-based guest molecules in cucu-bit[8]uril and covalent networks of oligoethylene glycol-(di)methacrylate. We also investigate the viscoelastic prop-erties of human brain tissues. The mechanical properties ofthe dual network gels are benchmarked against the humantissue, and we find that they both are neuro-mimetic and ex-hibit cytocompatiblity in a neural stem cell model.The Winston Churchill Foundation of the United States. The Newton International Fellowship

Cucurbit[8]uril-derived graphene hydrogels

The scalable production of uniformly distributed graphene (GR)-based composite materials remains a sizable challenge. While GR-polymer nanocomposites can be manufactured at large scale, processing limitations result in poor control over the homogeneity of hydrophobic GR sheets in the matrices. Such processes often result in difficulties controlling stability and avoiding aggregation, therefore eliminating benefits that might have otherwise arisen from the nanoscopic dimensions of GR. Here, we report an exfoliated and stabilized GR dispersion in water. Cucurbit[8]uril (CB[8])-mediated host guest chemistry was used to obtain supramolecular hydrogels consisting of uniformly distributed GR and guest-functionalized macromolecules. The obtained GR-hydrogels show superior bioelectrical properties over identical systems produced without CB[8]. Utilizing such supramolecular interactions with biologically-derived macromolecules is a promising approach to stabilize graphene in water and avoid oxidative chemistry.Marie Sklodowska-Curie individual research grant (H2020-MSCAIF- 2017, P.ID: 797106) The Winston Churchill Foundation of the United States EPSRC Doctoral Training Grant EP/N509620/1 EPSRC Programme Grant NOtCH (EP/L027151/1

Mechanical Characterization of Human Brain Tissue and SoftDynamic Gels Exhibiting Electromechanical Neuro-Mimicry

Synthetic hydrogels are an important class of materialsin tissue engineering, drug delivery, and other biomedicalfields. Their mechanical and electrical properties can betuned to match those of biological tissues. In this work,we report on hydrogels that exhibit both mechanical andelectrical biomimicry. The presented dual networks consistof supramolecular networks formed from 2:1 homoternarycomplexes of imidazolium-based guest molecules in cucu-bit[8]uril and covalent networks of oligoethylene glycol-(di)methacrylate. We also investigate the viscoelastic prop-erties of human brain tissues. The mechanical properties ofthe dual network gels are benchmarked against the humantissue, and we find that they both are neuro-mimetic and ex-hibit cytocompatiblity in a neural stem cell model.The Winston Churchill Foundation of the United States. The Newton International Fellowship

Cucurbit[8]uril-Derived Graphene Hydrogels

The scalable production of uniformly distributed graphene (GR)-based composite materials remains a sizable challenge. While GR-polymer nanocomposites can be manufactured at large scale, processing limitations result in poor control over the homogeneity of hydrophobic GR sheets in the matrices. Such processes often result in difficulties controlling stability and avoiding aggregation, therefore eliminating benefits that might have otherwise arisen from the nanoscopic dimensions of GR. Here, we report an exfoliated and stabilized GR dispersion in water. Cucurbit[8]uril (CB[8])-mediated hostguest chemistry was used to obtain supramolecular hydrogels consisting of uniformly distributed GR and guest-functionalized macromolecules. The obtained GR-hydrogels show superior bioelectrical properties over identical systems produced without CB[8]. Utilizing such supramolecular interactions with biologically-derived macromolecules is a promising approach to stabilize graphene in water and avoid oxidative chemistry.</div

Myeloid cell interferon secretion restricts Zika flavivirus infection of developing and malignant human neural progenitor cells.

Zika virus (ZIKV) can infect human developing brain (HDB) progenitors resulting in epidemic microcephaly, whereas analogous cellular tropism offers treatment potential for the adult brain cancer, glioblastoma (GBM). We compared productive ZIKV infection in HDB and GBM primary tissue explants that both contain SOX2+ neural progenitors. Strikingly, although the HDB proved uniformly vulnerable to ZIKV infection, GBM was more refractory, and this correlated with an innate immune expression signature. Indeed, GBM-derived CD11b+ microglia/macrophages were necessary and sufficient to protect progenitors against ZIKV infection in a non-cell autonomous manner. Using SOX2+ GBM cell lines, we found that CD11b+-conditioned medium containing type 1 interferon beta (IFNβ) promoted progenitor resistance to ZIKV, whereas inhibition of JAK1/2 signaling restored productive infection. Additionally, CD11b+ conditioned medium, and IFNβ treatment rendered HDB progenitor lines and explants refractory to ZIKV. These findings provide insight into neuroprotection for HDB progenitors as well as enhanced GBM oncolytic therapies