Nano-Biosensors for mRNA-Based Cell Sorting Using Intracellular Markers at the Early Stage of Cell Reprogramming.

Cell reprogramming and manufacturing have broad applications in tissue regeneration and disease treatment. However, many derived cell types lack unique cell surface markers for protein-based cell sorting, making it difficult to isolate these cells from mixed populations. Additionally, there is a need to identify and isolate cells of interest at the early stages of cell expansion.

Viscoelastic extracellular matrix enhances epigenetic remodeling and cellular plasticity.

Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function, compared to those on elastic surfaces.

Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies.

The use of synthetic antigen-presenting cells to activate and expand engineered T cells for the treatment of cancers typically results in therapies that are suboptimal in effectiveness and durability. Here we describe a high-throughput microfluidic system for the fabrication of synthetic cells mimicking the viscoelastic and T-cell-activation properties of antigen-presenting cells. Compared with rigid or elastic microspheres, the synthetic viscoelastic T-cell-activating cells (SynVACs) led to substantial enhancements in the expansion of human CD8 T cells and to the suppression of the formation of regulatory T cells.

Engineering programmable material-to-cell pathways via synthetic notch receptors to spatially control differentiation in multicellular constructs.

Synthetic Notch (synNotch) receptors are genetically encoded, modular synthetic receptors that enable mammalian cells to detect environmental signals and respond by activating user-prescribed transcriptional programs. Although some materials have been modified to present synNotch ligands with coarse spatial control, applications in tissue engineering generally require extracellular matrix (ECM)-derived scaffolds and/or finer spatial positioning of multiple ligands. Thus, we develop here a suite of materials that activate synNotch receptors for generalizable engineering of material-to-cell signaling.

Viscoelastic Extracellular Matrix Enhances Epigenetic Remodeling and Cellular Plasticity.

Extracellular matrices of living tissues exhibit viscoelastic properties, yet how these properties regulate chromatin and the epigenome remains unclear. Here, we show that viscoelastic substrates induce changes in nuclear architecture and epigenome, with more pronounced effects on softer surfaces. Fibroblasts on viscoelastic substrates display larger nuclei, lower chromatin compaction, and differential expression of distinct sets of genes related to the cytoskeleton and nuclear function compared to those on purely elastic surfaces.

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.

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.

Engineering Programmable Material-To-Cell Pathways Via Synthetic Notch Receptors To Spatially Control Cellular Phenotypes In Multi-Cellular Constructs.

Synthetic Notch (synNotch) receptors are modular synthetic components that are genetically engineered into mammalian cells to detect signals presented by neighboring cells and respond by activating prescribed transcriptional programs. To date, synNotch has been used to program therapeutic cells and pattern morphogenesis in multicellular systems. However, cell-presented ligands have limited versatility for applications that require spatial precision, such as tissue engineering.

Self-Powered Programming of Fibroblasts into Neurons via a Scalable Magnetoelastic Generator Array.

Developing scalable electrical stimulating platforms for cell and tissue engineering applications is limited by external power source dependency, wetting resistance, microscale size requirements, and suitable flexibility. Here, a versatile and scalable platform is developed to enable tunable electrical stimulation for biological applications by harnessing the giant magnetoelastic effect in soft systems, converting gentle air pressure (100-400 kPa) to yield a current of up to 10.5 mA and a voltage of 9.

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.

Intramuscular delivery of neural crest stem cell spheroids enhances neuromuscular regeneration after denervation injury.

Background: Muscle denervation from trauma and motor neuron disease causes disabling morbidities. A limiting step in functional recovery is the regeneration of neuromuscular junctions (NMJs) for reinnervation. Stem cells have the potential to promote these regenerative processes, but current approaches have limited success, and the optimal types of stem cells remain to be determined.

Asymmetric Cell Division of Fibroblasts is An Early Deterministic Step to Generate Elite Cells during Cell Reprogramming.

Cell reprogramming is considered a stochastic process, and it is not clear which cells are prone to be reprogrammed and whether a deterministic step exists. Here, asymmetric cell division (ACD) at the early stage of induced neuronal (iN) reprogramming is shown to play a deterministic role in generating elite cells for reprogramming. Within one day, fibroblasts underwent ACD, with one daughter cell being converted into an iN precursor and the other one remaining as a fibroblast.

Skeletal muscle regeneration via the chemical induction and expansion of myogenic stem cells in situ or in vitro.

Muscle loss and impairment resulting from traumatic injury can be alleviated by therapies using muscle stem cells. However, collecting sufficient numbers of autologous myogenic stem cells and expanding them efficiently has been challenging. Here we show that myogenic stem cells (predominantly Pax7 cells)-which were selectively expanded from readily obtainable dermal fibroblasts or skeletal muscle stem cells using a specific cocktail of small molecules and transplanted into muscle injuries in adult, aged or dystrophic mice-led to functional muscle regeneration in the three animal models.

Neural crest-like stem cells for tissue regeneration.

Neural crest stem cells (NCSCs) are a transient population of cells that arise during early vertebrate development and harbor stem cell properties, such as self-renewal and multipotency. These cells form at the interface of non-neuronal ectoderm and neural tube and undergo extensive migration whereupon they contribute to a diverse array of cell and tissue derivatives, ranging from craniofacial tissues to cells of the peripheral nervous system. Neural crest-like stem cells (NCLSCs) can be derived from pluripotent stem cells, placental tissues, adult tissues, and somatic cell reprogramming.

Photodegradable Polyacrylamide Gels for Dynamic Control of Cell Functions.

Cross-linked polyacrylamide hydrogels are commonly used in biotechnology and cell culture applications due to advantageous properties, such as the precise control of material stiffness and the attachment of cell adhesive ligands. However, the chemical and physical properties of polyacrylamide gels cannot be altered once fabricated. Here, we develop a photodegradable polyacrylamide gel system that allows for a dynamic control of polyacrylamide gel stiffness with exposure to light.

Mechanical regulation of histone modifications and cell plasticity.

Cell plasticity is important in development and tissue remodeling. Cells can sense physical and chemical cues from their local microenvironment and transduce the signals into the nucleus to regulate the epigenetic state and gene expression, resulting in a change in cell phenotype. In this review, we highlight the role of mechanical cues in regulating stem cell differentiation and cell reprogramming through the modulation of histone modifications.

Engineering Biomaterials with Micro/Nanotechnologies for Cell Reprogramming.

Cell reprogramming is a revolutionized biotechnology that offers a powerful tool to engineer cell fate and function for regenerative medicine, disease modeling, drug discovery, and beyond. Leveraging advances in biomaterials and micro/nanotechnologies can enhance the reprogramming performance and through the development of delivery strategies and the control of biophysical and biochemical cues. In this review, we present an overview of the state-of-the-art technologies for cell reprogramming and highlight the recent breakthroughs in engineering biomaterials with micro/nanotechnologies to improve reprogramming efficiency and quality.

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.

Biophysical regulation of cell reprogramming.

Induced pluripotent stem (iPS) cell reprogramming and direct reprogramming are promising approaches for disease modeling and personalized medicine. However, these processes are yet to be optimized. Biomaterials are increasingly integrated into cell reprogramming strategies in order to engineer the microenvironment, improve reprogramming efficiency and achieve effective in situ cell reprogramming.

Axon contact-driven Schwann cell dedifferentiation.

Mature Schwann cells (SCs) retain dedifferentiation potential throughout adulthood. Still, how dedifferentiation occurs remains uncertain. Results from a variety of cell-based assays using in vitro cultured cAMP-differentiated and myelinating SCs revealed the existence of a novel dedifferentiating activity expressed on the surface of dorsal root ganglion (DRG) axons.

Biophysical regulation of epigenetic state and cell reprogramming.

Biochemical factors can help reprogram somatic cells into pluripotent stem cells, yet the role of biophysical factors during reprogramming is unknown. Here, we show that biophysical cues, in the form of parallel microgrooves on the surface of cell-adhesive substrates, can replace the effects of small-molecule epigenetic modifiers and significantly improve reprogramming efficiency. The mechanism relies on the mechanomodulation of the cells' epigenetic state.

Schwann cell dedifferentiation is independent of mitogenic signaling and uncoupled to proliferation: role of cAMP and JNK in the maintenance of the differentiated state.

Myelinating Schwann cells (SCs) are highly plastic cells that are able to dedifferentiate and re-enter the cell cycle. However, the molecular signals controlling dedifferentiation are not completely understood. Because a connection between mitogenic signaling and myelin loss has been suggested, we investigated the role of cAMP, a strong inducer of the myelinating phenotype, and mitogenic factors activating receptor tyrosine kinases (RTKs) on SC dedifferentiation.