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Organ-on-a-chip (OOC) devices mimic human organs, which can be used for many different applications, including drug development, environmental toxicology, disease models, and physiological assessment. Image data acquisition and analysis from these chips are crucial for advancing research in the field. In this study, we propose a label-free morphology imaging platform compatible with the small airway-on-a-chip system. By integrating deep learning and image recognition techniques, we aim to analyze the differentiability of human small airway epithelial cells (HSAECs). Utilizing cell imaging on day 3 of culture, our approach accurately predicts the differentiability of HSAECs after 4 weeks of incubation. This breakthrough significantly enhances the efficiency and stability of establishing small airway-on-a-chip models. To further enhance our analysis capabilities, we have developed a customized MATLAB program capable of automatically processing ciliated cell beating images and calculating the beating frequency. This program enables continuous monitoring of ciliary beating activity. Additionally, we have introduced an automated fluorescent particle tracking system to evaluate the integrity of mucociliary clearance and validate the accuracy of our deep learning predictions. The integration of deep learning, label-free imaging, and advanced image analysis techniques represents a significant advancement in the fields of drug testing and physiological assessment. This innovative approach offers unprecedented insights into the functioning of the small airway epithelium, empowering researchers with a powerful tool to study respiratory physiology and develop targeted interventions.

Graphene oxide-based materials (GOBMs) have been widely explored as nano-reinforcements in cementitious composites due to their unique properties. Oxygen-containing functional groups in GOBMs are crucial for enhancing the microstructure of cementitious composites. A better comprehension of their surface chemistry and mechanisms is required to advance the potential applications in cementitious composites of functionalized GOBMs. However, the mechanism by which the oxygen-containing functional groups enhance the response of cementitious composites is still unclear, and controlling the surface chemistry of GOBMs is currently constrained. This review aims to investigate the reactions and mechanisms for functionalized GOBMs as additives incorporated in cement composites. A variety of GOBMs, including graphene oxide (GO), hydroxylated graphene (HO-G), edge-carboxylated graphene (ECG), edge-oxidized graphene oxide (EOGO), reduced graphene oxide (rGO), and GO/silane composite, are discussed with regard to their oxygen functional groups and interactions with the cement microstructure. This review provides insight into the potential benefits of using GOBMs as nano-reinforcements in cementitious composites. A better understanding of the surface chemistry and mechanisms of GOBMs will enable the development of more effective functionalization strategies and open up new possibilities for the design of high-performance cementitious composites.

Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; however, suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking. In this paper, we present a standardized primary alveolar cell culture method for establishing a human alveolar epithelium model that can recapitulate viral infection and cellular plasticity. The alveolar model is infected with a SARS-CoV-2 pseudovirus, and the clinically relevant features of the viral entry into the alveolar type-I/II cells, cytokine production activation, and pulmonary surfactant destruction are reproduced. For this damaged alveolar model, we find that the inhibition of Wnt signaling via XAV939 substantially improves alveolar repair function and prevents subsequent pulmonary fibrosis. Thus, the proposed alveolar cell culture strategy exhibits potential for the identification of pathogenesis and therapeutics in basic and translational research. Yang et al. present an alveolar cell culture method that utilizes primary human alveolar epithelial cells, culturing cells in a small-molecule cocktail supplemented media. The authors show that the longevity of the primary cells culture can be expanded, and study human alveolar development, infection, injury repair, while demonstrating its use for SARS-CoV-2 infection.

As the most prevalent structural protein in the extracellular matrix, collagen has been extensively investigated for biofabrication-based applications. However, its utilisation has been impeded due to a lack of sufficient mechanical toughness and the inability of the scaffold to mimic complex natural tissues. The anisotropic alignment of collagen fibres has been proven to be an effective method to enhance its overall mechanical properties and produce biomimetic scaffolds. This review introduces the complicated scenario of collagen structure, fibril arrangement, type, function, and in addition, distribution within the body for the enhancement of collagen-based scaffolds. We describe and compare existing approaches for the alignment of collagen with a sharper focus on electro-compaction. Additionally, various effective processes to further enhance electro-compacted collagen, such as crosslinking, the addition of filler materials, and post-alignment fabrication techniques, are discussed. Finally, current challenges and future directions for the electro-compaction of collagen are presented, providing guidance for the further development of collagenous scaffolds for bioengineering and nanotechnology.

Hydrogels composed of calcium cross-linked alginate are under investigation as bioinks for tissue engineering scaffolds due to their variable viscoelasticity, biocompatibility, and erodibility. Here, pyrrole was oxidatively polymerized in the presence of sodium alginate solutions to form ionomeric composites of various compositions. The IR spectroscopy shows that mild base is required to prevent the oxidant from attacking the alginate during the polymerization reaction. The resulting composites were isolated as dried thin films or cross-linked hydrogels and aerogels. The products were characterized by elemental analysis to determine polypyrrole incorporation, electrical conductivity measurements, and by SEM to determine changes in morphology or large-scale phase separation. Polypyrrole incorporation of up to twice the alginate (monomer versus monomer) provided materials amenable to 3D extrusion printing. The PC12 neuronal cells adhered and proliferated on the composites, demonstrating their biocompatibility and potential for tissue engineering applications.

Melt-electrowriting (MEW) is an emerging method that combines electrospinning and extrusion printing, allowing the fabrication of micron-scale structures suitable for tissue engineering. Compared to other additive fabrication methods, melt-electro written structures can offer more appropriate substrates for cell culture due to filament size and mechanical characteristics of the fabricated scaffolds. In this study, polycaprolactone (PCL)/graphene composites were investigated for fabrication of micron-size scaffolds through MEW. It was demonstrated that the addition of graphene can considerably improve the processability of PCL to fabricate micron-scale scaffolds with enhanced resolution. The tensile strength of the scaffold prepared from PCL/graphene composite (with only 0.5 wt.% graphene) was proved significantly (by more than 270%), better than that of the pristine PCL scaffold. Furthermore, graphene was demonstrated to be a suitable material for tailoring the degradation process to avoid undesirable bulk degradation, rapid mass loss and damage to the internal matrix of the polymer. The findings of this study offer a promising route for the fabrication of high-resolution scaffolds with micron-scale resolution for tissue engineering.

Retinal prosthesis has recently emerged as a treatment strategy for retinopathies, providing excellent assistance in the treatment of age-related macular degeneration (AMD) and retinitis pigmentosa. The potential application of graphene oxide (GO), a highly biocompatible nanomaterial with superior physicochemical properties, in the fabrication of electrodes for retinal prosthesis, is reviewed in this article. This review integrates insights from biological medicine and nanotechnology, with electronic and electrical engineering technological breakthroughs, and aims to highlight innovative objectives in developing biomedical applications of retinal prosthesis.

Polymer clay nanocomposites (NCs) show remarkable potential in the field of drug delivery due to their enhanced barrier properties. It is hypothesised that well dispersed clay particles within the polymer matrix create a tortuous pathway for diffusing therapeutic molecules, thereby resulting in more sustained release of the drug. As coatings for medical devices, these materials can simultaneously modulate drug release and improve the mechanical performance of an existing polymer system without introducing additional materials with new chemistries that can lead to regulatory concerns. In this study, polyurethane organosilicate nanocomposites (PUNCs) coated onto stainless steel wires were evaluated for their feasibility as blood compatible coatings and as drug delivery systems. Heparin was selected as the model drug to examine the impact of silicate loading and modifier chain length in modulating release. Findings revealed that better dispersion was achieved from samples with lower clay loadings and longer alkyl chains. The blood compatibility of PUNCs as assessed by thrombin generation assays showed that the addition of silicate particles did not significantly decrease the thrombin generation lag time (TGT, p = 0.659) or the peak thrombin (p = 0.999) of polyurethane (PU). PUNC coatings fabricated in this research were not cytotoxic as examined by the cell growth inhibition assay and were uniformly intact, but had slightly higher growth inhibition compared to PU possibly due to the presence of organic modifiers (OM). The addition of heparin into PUNCs prolonged the TGT, indicating that heparin was still active after the coating process. Cumulative heparin release profiles showed that the majority of heparin released was from loosely attached residues on the surface of coils. The addition of heparin further prolonged the TGT as compared to coatings without added heparin, but a slight decrease in heparin activity was observed in the NCs. This was thought to be from competitive interactions between clay-heparin that influenced the formation of the ternary complex between heparin, ATIII thrombin. In summary, the feasibility of using PUNC as drug delivery coatings was shown by the good uniformity in the coating, absence of by-products from the coating process, and the release of active molecules without significantly interfering with their activity.

Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (⩾4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.

α-Synuclein (αSyn), an intrinsically disordered protein implicated in Parkinson’s disease, is thought to initiate aggregation by binding to cellular membranes. Previous studies suggest that anionic lipids are necessary for this binding. However, these studies largely focused on unmodified αSyn, while physiological αSyn is N-terminally acetylated (NTA). Our work challenges the long-standing paradigm that anionic lipids are necessary for αSyn binding by demonstrating that NTA diminishes αSyn’s reliance on anionic membranes, revealing that membrane packing defects (i.e., interfacial hydrophobicity) alone can drive membrane binding. Using fluorescence microscopy and circular dichroism spectroscopy, we monitored the binding of NTA-αSyn to membrane vesicles with different lipid compositions. Phosphatidylcholine and phosphatidylserine concentrations were varied to control surface charge, while phospholipid tail unsaturation and methylation were varied to modulate lipid packing. We also formulated cholesterol-containing membranes that mimicked the lipid composition of synaptic vesicles. In these membranes, all-atom molecular dynamics simulations were used to visualize and quantify membrane packing defects. Our results demonstrate that membrane packing defects are necessary for NTA-αSyn binding and that defect-rich membranes are sufficient for NTA-αSyn binding regardless of membrane charge. These findings provide a molecular mechanism by which lipid structural properties, such as poly-unsaturation, can regulate αSyn binding to physiological membranes. Mechanistic analysis of α-synuclein binding clarifies the roles of lipid packing defects and charge in regulating membrane interactions.