In Vitro Modeling of Idiopathic Pulmonary Fibrosis: Lung-on-a-Chip Systems and Other 3D Cultures.

Idiopathic pulmonary fibrosis (IPF) is a lethal disorder characterized by relentless progression of lung fibrosis that causes respiratory failure and early death. Currently, no curative treatments are available, and existing therapies include a limited selection of antifibrotic agents that only slow disease progression. The development of novel therapeutics has been hindered by a limited understanding of the disease's etiology and pathogenesis.

Targeting nanoparticles to lung cancer-derived A549 cells based on changes on interstitial stiffness in biomimetic models.

The mechanical properties and forces of the extracellular environment modulate alveolar epithelial cell behavior. To model cancer/fibrosis associated stiffening and dynamic stretch, a biomimetic device was developed that imitates the active forces in the alveolus, while allowing control over the interstitial matrix stiffness. Alveolar epithelial A549 cancer cells were cultured on the devices and their transcriptome was profiled with RNA sequencing.

Biocompatible Co-P Metallic Glasses with Superior Degradation Tolerance in Physiological Environments.

Metallic glasses represent a class of metallic alloys with a fully amorphous structure and attractive properties, making them promising in bioimplant applications. Here, the degradation tolerance of biocompatible cobalt-phosphorus (Co-P) metallic glasses was studied in a simulated physiological environment. The metallic glasses were synthesized in the form of coatings through a facile electrodeposition approach.

Surface Nanostructures Enhanced Biocompatibility and Osteoinductivity of Laser-Additively Manufactured CoCrMo Alloys.

Cobalt-chromium-molybdenum (CoCrMo) alloys are widely used in orthopedic implants due to their excellent corrosion and wear resistance and superior mechanical properties. However, their limited capability to promote cell adhesion and new bone tissue formation, poor blood compatibility, and risk of microbial infection can lead to implant failure or reduced implant lifespan. Surface structure modification has been used to improve the cytocompatibility and blood compatibility of implant materials and reduce the risk of infection.

Detergent-Based Decellularization for Anisotropic Cardiac-Specific Extracellular Matrix Scaffold Generation.

Cell-derived extracellular matrix (ECM) has become increasingly popular in tissue engineering applications due to its ability to provide tailored signals for desirable cellular responses. Anisotropic cardiac-specific ECM scaffold decellularized from human induced pluripotent stem cell (hiPSC)-derived cardiac fibroblasts (hiPSC-CFs) mimics the native cardiac microenvironment and provides essential biochemical and signaling cues to hiPSC-derived cardiomyocytes (hiPSC-CMs). The objective of this study was to assess the efficacy of two detergent-based decellularization methods: (1) a combination of ethylenediaminetetraacetic acid and sodium dodecyl sulfate (EDTA + SDS) and (2) a combination of sodium deoxycholate and deoxyribonuclease (SD + DNase), in preserving the composition and bioactive substances within the aligned ECM scaffold while maximumly removing cellular components.

Nanofibrous Membrane Promotes and Sustains Vascular Endothelial Barrier Function.

The vascular endothelium serves as a physical barrier between the circulating blood and surrounding tissue and acts as a critical regulator of various physiological processes. models involving vasculature rely on the maintenance of the endothelial barrier function. In this study, we fabricated 2D aligned nanofibrous membranes with distinct pore sizes via electrospinning and investigated the effect of membrane pore size on endothelial barrier function.

Nanotopographical Cues Tune the Therapeutic Potential of Extracellular Vesicles for the Treatment of Aged Skeletal Muscle Injuries.

Skeletal muscle regeneration relies on the tightly temporally regulated lineage progression of muscle stem/progenitor cells (MPCs) from activation to proliferation and, finally, differentiation. However, with aging, MPC lineage progression is disrupted and delayed, ultimately causing impaired muscle regeneration. Extracellular vesicles (EVs) have attracted broad attention as next-generation therapeutics for promoting tissue regeneration.

Biomimetic Human Lung Alveolar Interstitium Chip with Extended Longevity.

Determining the mechanistic causes of lung diseases, developing new treatments thereof, and assessing toxicity whether from chemical exposures or engineered nanomaterials would benefit significantly from a preclinical human lung alveolar interstitium model of physiological relevance. The existing preclinical models have limitations because they fail to replicate the key anatomical and physiological characteristics of human alveoli. Thus, a human lung alveolar interstitium chip was developed to imitate key alveolar microenvironmental factors including an electrospun nanofibrous membrane as the analogue of the basement membrane for co-culture of epithelial cells with fibroblasts embedded in 3D collagenous gels, physiologically relevant interstitial matrix stiffness, interstitial fluid flow, and 3D breathing-like mechanical stretch.

Microstructure enhanced biocompatibility in laser additively manufactured CoCrMo biomedical alloy.

The present work investigated biocompatibility of the unique nanostructural surface morphology inherently evolved in laser-based additively manufactured CoCrMo after biocorrosion in simulated body fluid at physiological temperature (37 °C). The extremely rapid thermokinetics intrinsically associated with the laser-based additive manufacturing technique resulted in heterogeneous cellular dendritic solidification morphologies with selective elemental segregation along the cell boundaries within CoCrMo samples. Consequently, a selective and spatially varying electrochemical response resulted in generation of a nanoscale surface morphology (crests and troughs) due to differential localized electrochemical etching.

Nanoparticle targeting of mechanically modulated glycocalyx.

The mechanical properties and forces in the extracellular environment surrounding alveolar epithelial cells have the potential to modulate their behavior. Particularly, breathing applies 3-dimensional cyclic stretches to the cells, while the stiffness of the interstitium changes in disease states, such as fibrosis and cancer. A platform was developed that effectively imitates the active forces in the alveolus, while allowing one to control the interstitium matrix stiffnesses to mimic fibrotic lung tumor microenvironments.

Dissecting Physical and Biochemical Effects in Nanotopographical Regulation of Cell Behavior.

Regulating cell behavior using nanotopography has been widely implemented. To facilitate cell adhesion, physical nanotopography is usually coated with adhesive proteins such as fibronectin (FN). However, the confounding effects of physical and biochemical cues of nanotopography hinder the understanding of nanotopography in regulating cell behavior, which ultimately limits the biomedical applications of nanotopography.

Dimensionality-Dependent Mechanical Stretch Regulation of Cell Behavior.

A variety of cells are subject to mechanical stretch , which plays a critical role in the function and homeostasis of cells, tissues, and organs. Deviations from the physiologically relevant mechanical stretch are often associated with organ dysfunction and various diseases. Although mechanical stretch is provided in some cell culture models, the effects of stretch dimensionality on cells are often overlooked and it remains unclear whether and how stretch dimensionality affects cell behavior.

Microphysiological Systems: Design, Fabrication, and Applications.

Microphysiological systems, including organoids, 3-D printed tissue constructs and organ-on-a-chips (organ chips), are physiologically relevant models and have experienced explosive growth in the past decades. Different from conventional, tissue culture plastic-based models or animal models, microphysiological systems recapitulate key microenvironmental characteristics of human organs and mimic their primary functions. The advent of microphysiological systems is attributed to evolving biomaterials, micro-/nanotechnologies and stem cell biology, which enable the precise control over the matrix properties and the interactions between cells, tissues and organs in physiological conditions.

biomineralization and biocompatibility of friction stir additively manufactured AZ31B magnesium alloy-hydroxyapatite composites.

The present study aims to evaluate effect of hydroxyapatite (HA, Ca(PO)OH), a ceramic similar to natural bone, into AZ31B Mg alloy matrix on biomineralization and biocompatibility. The novel friction stir processing additive manufacturing route was employed to fabricate Mg-HA composites. Various HA contents (5, 10, 20 wt%) were incorporated into Mg matrix.

Substrate Stiffness-Dependent Carbon Nanotube-Induced Lung Fibrogenesis.

Most living tissues exhibit the specific stiffness, which has been known to have profound influence on cell behaviors, yet how the stiffness affects cellular responses to engineered nanomaterials has not been elucidated. Particularly, discrepancies exist between and nanotoxicological studies. Here, we investigated the effects of substrate stiffness on the fibrogenic responses of normal human lung fibroblasts (NHLFs) to multiwalled carbon nanotubes (MWCNTs).

Cell attenuated porcine epidemic diarrhea virus strain Zhejiang08 provides effective immune protection attributed to dendritic cell stimulation.

Since 2010, the porcine epidemic diarrhea coronavirus (PEDV) has caused significant damage to the global pork industry. However, classical PEDV vaccine strains only provide limited protection against emerging strains. In this study, we successfully isolated and attenuated the PEDV epidemic strain Zhejiang08, which was characterized by good cell adaptation and high-titer production 48 h post infection in Vero E6 cells.