Engineering Materials and Devices for the Prevention, Diagnosis, and Treatment of COVID-19 and Infectious Diseases.

Following the global spread of COVID-19, scientists and engineers have adapted technologies and developed new tools to aid in the fight against COVID-19. This review discusses various approaches to engineering biomaterials, devices, and therapeutics, especially at micro and nano levels, for the prevention, diagnosis, and treatment of infectious diseases, such as COVID-19, serving as a resource for scientists to identify specific tools that can be applicable for infectious-disease-related research, technology development, and treatment. From the design and production of equipment critical to first responders and patients using three-dimensional (3D) printing technology to point-of-care devices for rapid diagnosis, these technologies and tools have been essential to address current global needs for the prevention and detection of diseases. Moreover, advancements in organ-on-a-chip platforms provide a valuable platform to not only study infections and disease development in humans but also allow for the screening of more effective therapeutics. In addition, vaccines, the repurposing of approved drugs, biomaterials, drug delivery, and cell therapy are promising approaches for the prevention and treatment of infectious diseases. Following a comprehensive review of all these topics, we discuss unsolved problems and future directions.

Reduction of Intracellular Tension and Cell Adhesion Promotes Open Chromatin Structure and Enhances Cell Reprogramming.

The role of transcription factors and biomolecules in cell type conversion has been widely studied. Yet, it remains unclear whether and how intracellular mechanotransduction through focal adhesions (FAs) and the cytoskeleton regulates the epigenetic state and cell reprogramming. Here, it is shown that cytoskeletal structures and the mechanical properties of cells are modulated during the early phase of induced neuronal (iN) reprogramming, with an increase in actin cytoskeleton assembly induced by Ascl1 transgene. The reduction of actin cytoskeletal tension or cell adhesion at the early phase of reprogramming suppresses the expression of mesenchymal genes, promotes a more open chromatin structure, and significantly enhances the efficiency of iN conversion. Specifically, reduction of intracellular tension or cell adhesion not only modulates global epigenetic marks, but also decreases DNA methylation and heterochromatin marks and increases euchromatin marks at the promoter of neuronal genes, thus enhancing the accessibility for gene activation. Finally, micro- and nano-topographic surfaces that reduce cell adhesions enhance iN reprogramming. These novel findings suggest that the actin cytoskeleton and FAs play an important role in epigenetic regulation for cell fate determination, which may lead to novel engineering approaches for cell reprogramming.

Transient nuclear deformation primes epigenetic state and promotes cell reprogramming.

Cell reprogramming has wide applications in tissue regeneration, disease modelling and personalized medicine. In addition to biochemical cues, mechanical forces also contribute to the modulation of the epigenetic state and a variety of cell functions through distinct mechanisms that are not fully understood. Here we show that millisecond deformation of the cell nucleus caused by confinement into microfluidic channels results in wrinkling and transient disassembly of the nuclear lamina, local detachment of lamina-associated domains in chromatin and a decrease of histone methylation (histone H3 lysine 9 trimethylation) and DNA methylation. These global changes in chromatin at the early stage of cell reprogramming boost the conversion of fibroblasts into neurons and can be partially reproduced by inhibition of histone H3 lysine 9 and DNA methylation. This mechanopriming approach also triggers macrophage reprogramming into neurons and fibroblast conversion into induced pluripotent stem cells, being thus a promising mechanically based epigenetic state modulation method for cell engineering.

Cell engineering: Biophysical regulation of the nucleus.

Cells live in a complex and dynamic microenvironment, and a variety of microenvironmental cues can regulate cell behavior. In addition to biochemical signals, biophysical cues can induce not only immediate intracellular responses, but also long-term effects on phenotypic changes such as stem cell differentiation, immune cell activation and somatic cell reprogramming. Cells respond to mechanical stimuli via an outside-in and inside-out feedback loop, and the cell nucleus plays an important role in this process. The mechanical properties of the nucleus can directly or indirectly modulate mechanotransduction, and the physical coupling of the cell nucleus with the cytoskeleton can affect chromatin structure and regulate the epigenetic state, gene expression and cell function. In this review, we will highlight the recent progress in nuclear biomechanics and mechanobiology in the context of cell engineering, tissue remodeling and disease development.