A novel magnetic hydrogel is formed via the field-directed assembly of magnetic nanomaterials during the gelation process. The novel magnetic hydrogel exhibits direction-dependent thermogenesis in an alternating magnetic field. The specific absorption rate value in the direction along the assemblies can be 2.1-fold as much as that in the direction normal to the assemblies while the heating rate is 6-8-fold. Due to the anisotropic thermogenesis, the novel magnetic hydrogel also shows a direction-dependent release of drugs that has a 3.4-fold difference between the two directions.
Cell-adhesive properties are of great significance to materials serving as extracellular matrix mimics. Appropriate cell-adhesive property of material interface can balance the cell-matrix interaction and cell-cell interaction and can promote cells to form 3D structures. Herein, a novel magnetic polyacrylamide (PAM) hydrogel fabricated via combining magnetostatic field induced magnetic nanoparticles assembly and hydrogel gelation was applied as a multicellular spheroids culturing platform. When cultured on the cell-adhesive microarray interface of sliced magnetic hydrogel, normal and tumor cells from different cell lines could rapidly form multicellular spheroids spontaneously. Furthermore, cells which could only form loose cell aggregates in a classic 3D cell culture model (such as hanging drop system) were able to be promoted to form multicellular spheroids on this platform. In the light of its simplicity in fabricating as well as its effectiveness in promoting formation of multicellular spheroids which was considered as a prevailing tool in the study of the microenvironmental regulation of tumor cell physiology and therapeutic problems, this composite material holds promise in anticancer drugs or hyperthermia therapy evaluation in vitro in the future.
For mimicking the fibrous extracellular matrix (ECM), a facile method for patterning anticell adhesive substrate was novelly applied on agarose hydrogel. Without using masks or templates for etching, we applied the magnetic field-induced colloidal assembly of magnetic nanoparticles on the flat agarose hydrogel to form cell-adhesive micropatterns. Meanwhile, tuning the hydrogel substrate's modulus to fit real tissue was experimentally demonstrated. Magnetic nanobeads were also assembled on this hydrogel surface and formed more complete and regular patterns. The patterned hydrogel substrate could actually influence behaviors of different cancer cells, including adhesion, growth, and migration.
BACKGROUND. Some clinical features of severe COVID-19 represent blood vessel damage induced by activation of host immune responses initiated by the coronavirus SARS-CoV-2. We hypothesized autoantibodies against angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor expressed on vascular endothelium, are generated during COVID-19 and are of mechanistic importance.
METHODS.In an opportunity sample of 118 COVID-19 inpatients, autoantibodies recognizing ACE2 were detected by ELISA. Binding properties of anti-ACE2 IgM were analyzed via biolayer interferometry. Effects of anti-ACE2 IgM on complement activation and endothelial function were demonstrated in a tissue-engineered pulmonary microvessel model.
RESULTS.Anti-ACE2 IgM (not IgG) autoantibodies were associated with severe COVID-19 and found in 18/66 (27.2%) patients with severe disease compared with 2/52 (3.8%) of patients with moderate disease (OR 9.38, 95% CI 2.38-42.0; P = 0.0009). Anti-ACE2 IgM autoantibodies were rare (2/50) in non-COVID-19 ventilated patients with acute respiratory distress syndrome. Unexpectedly, ACE2reactive IgM autoantibodies in COVID-19 did not undergo class-switching to IgG and had apparent K D values of 5.6-21.7 nM, indicating they are T cell independent. Anti-ACE2 IgMs activated complement and initiated complement-binding and functional changes in endothelial cells in microvessels, suggesting they contribute to the angiocentric pathology of COVID-19.
CONCLUSION.We identify anti-ACE2 IgM as a mechanism-based biomarker strongly associated with severe clinical outcomes in SARS-CoV-2 infection, which has therapeutic implications.
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