Search

Endothelial dysfunction is a critical feature of acute respiratory distress syndrome (ARDS) associated with higher disease severity and worse outcomes. Preclinical in vivo models of sepsis and ARDS have failed to yield useful therapies in humans, perhaps due to interspecies differences in inflammatory responses and heterogeneity of human host responses. Use of microphysiological systems (MPS) to investigate lung endothelial function may shed light on underlying mechanisms and targeted treatments for ARDS. We assessed the response to plasma from critically ill sepsis patients in our lung endothelial MPS through measurement of endothelial permeability, expression of adhesion molecules, and inflammatory cytokine secretion. Sepsis plasma induced areas of endothelial cell (EC) contraction, loss of cellular coverage, and luminal defects. EC barrier function was significantly worse following incubation with sepsis plasma compared to healthy plasma. EC ICAM-1 expression, IL-6 and soluble ICAM-1 secretion increased significantly more after incubation with sepsis plasma compared with healthy plasma. Plasma from sepsis patients who developed ARDS further increased IL-6 and sICAM-1 compared to plasma from sepsis patients without ARDS and healthy plasma. Our results demonstrate the proof of concept that lung endothelial MPS can enable interrogation of specific mechanisms of endothelial dysfunction that promote ARDS in sepsis patients., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Multidrug resistance (MDR) has been considered as a major adversary in oncologic chemotherapy. To simultaneously overcome drug resistance and inhibit tumor growth, it is essential to develop a drug delivery system that can carry and release multiple therapeutic agents with spatiotemporal control. In this study, we developed a hydrogel containing an enzyme-cleavable peptide motif, with a network structure formed by 4-armed polyethylene glycol (PEG) crosslinked by complementary nucleic acid sequences. Hydrogen bond formation between nucleobase pairing allows the hydrogel to be injectable, and the peptide motif grants deliberate control over hydrogel degradation and the responsive drug release. Moreover, MDR-targeted siRNAs are complexed with stearyl-octaarginine (STR-R8), while doxorubicin (Dox) is intercalated with DNA and nanoclay structures in this hydrogel to enhance therapeutic efficacy and overcome MDR. The results show a successful configuration of a hydrogel network with in situ gelation property, injectability, and degradability in the presence of tumor-associated enzyme, MMP-2. The synergistic effect by combining MDR-targeted siRNAs and Dox manifests with the enhanced anti-cancer effect on drug resistant breast cancer cells in both in vitro and in vivo tumor models. We suggest that with the tailor-designed hydrogel system, multidrug resistance in tumor cells can be significantly inhibited by the co-delivery of multiple therapeutics with spatial-temporal control release., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Exosomes are extracellular vesicles that share components of their parent cells and are attractive in biotechnology and biomedical research as potential disease biomarkers as well as therapeutic agents. Crucial to realizing this potential is the ability to manufacture high-quality exosomes; however, unlike biologics such as proteins, exosomes lack standardized Good Manufacturing Practices for their processing and characterization. Furthermore, there is a lack of well-characterized reference exosome materials to aid in selection of methods for exosome isolation, purification, and analysis. This review informs exosome research and technology development by comparing exosome processing and characterization methods and recommending exosome workflows. This review also provides a detailed introduction to exosomes, including their physical and chemical properties, roles in normal biological processes and in disease progression, and summarizes some of the on-going clinical trials., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Heterogeneous tissue models require the assembly and co-culture of multiple types of cells. Our recent work demonstrated taste signal transmission from gustatory cells to neurons by grafting single-stranded DNA into the cell membrane to construct multicellular assemblies. However, the weak DNA linkage and low grafting density allowed the formation of large gustatory cell self-aggregates that cannot communicate with neurons efficiently. This article presents the construction of artificial taste buds exhibiting active intercellular taste signal transmission through the hybridization of gustatory-neuronal multicellular interfaces using bioorthogonal click chemistry. Hybrid cell clusters were formed by the self-assembly of neonatal gustatory cells displaying tetrazine with a precultured embryonic hippocampal neuronal network displaying trans-cyclooctene. A bitter taste signal transduction was provoked in gustatory cells using denatonium benzoate and transmitted to neurons as monitored by intracellular calcium ion sensing. In the multicellular hybrids, the average number of signal transmissions was five to six peaks per cell, and the signal transmission lasted for ∼5 min with a signal-to-signal gap time of 10-40 s. The frequent and extended intercellular signal transmission suggests that the cell surface modification by the bioorthogonal click chemistry is a promising approach to fabricating functional multicellular hybrid clusters potentially useful for cell-based biosensors, toxicity assays, and tissue regeneration.

During nervous system development, an extracellular matrix (ECM) plays a pivotal role through surface topography and microenvironment signals in neurons and neurites maturation. Topography and microenvironment signals act as physical and chemical guiding cues, respectively, for neural tissue formation and reconstruction. Imposed surface topography can affect neural stem cells by promoting adhesion, spreading, alignment, morphological changes, and specific gene expression. Therefore, fabrication of a biomimetic construct or scaffold to support neurite outgrowth and axon extension is a crucial and common strategy for neural tissue regeneration. Here, we review recent developments in biomaterials modification for simulating the microenvironment to promote neural cell adhesion and growth. The subtopics include those of potential cellular mechanisms of topographical response, topography on cellular organization and function, contact guidance in neurite outgrowth and axon growth, ECM microenvironment as regulatory cues, as well as challenges and future perspectives of nerve conduits that are now in clinical trials and usage.

Objective: To study the role of different scale structure of Ti implants on the biological behaviors of human umbilical vein endothelial cell (HUVECs) and to reveal the role of material surface topographical features on peri-implant angiogenesis., Methods: Titanium (Ti) discs with different surface structures (Ti discs with smooth surface, Ti discs with nano scale structure, Ti discs with micro scale structure and Ti discs with micro/nano scale structure, named as SM-Ti, Nano-Ti, Micro-Ti and Micro/Nano-Ti, respectively) were prepared and their surface topographical features were confirmed via scanning electron microscopy (SEM) observation. HUVECs were cultured on these Ti discs. Biological outcomes of HUVECs on different surfaces were carried out, including cell adhesive capacity, proliferation, vascular endothelial growth factor (VEGF) production and intracellular expression of Ca(2+)., Results: The results of SEM images and immunofluorescence double staining of rhodamine-phalloidin and DAPI showed that compared with the SM-Ti and Nano-Ti group, the adhesive capacity and proliferation behavior of HUVECs on the surfaces of Micro-Ti and Micro/Nano-Ti was decreased. The results of culturing HUVECs on different groups of Ti discs after 24 hours showed that the cells number grew from (18±4) to (42±6)/ vision on SM-Ti, (28±6) to (52±10)/vision on Nano-Ti, (20±4) to (21±6)/vision on Micro-Ti and (16±4) to (18±6)/vision on Micro/Nano-Ti. Moreover, compared with the adhesion and proliferation of HUVECs on SM-Ti group and Nano-Ti, the adhesion and proliferation of HUVECs on Micro-Ti group and Micro/Nano-Ti group was significantly reduced (P<0.05).The results of enzyme-linked immunosorbent assay (ELISA) showed that the VEGF productions of SM-Ti, Nano-Ti, Micro-Ti and Micro/Nano-Ti were (690±35) ng/L, (560±20) ng/L, (474±43) ng/L and (517±29) ng/L, respectively. Moreover, compared with the VEGF production of HUVECs on SM-Ti group, the VEGF production of HUVECs on Micro-Ti group and Micro/Nano-Ti group was significantly reduced (P<0.05). The results of Ca(2+) ion detection showed that the Ca(2+) expression of HUVECs on Micro-Ti and Micro/Nano-Ti was significantly higher than that on the surface of SM-Ti and Nano-Ti. These results implied that the over expressed Ca(2+) might contributed to the impaired biological function of HUVECs on Micro-Ti and Micro/Nano-Ti., Conclusion: Different topographical features on titanium influenced the biological behaviors of the HUVECs, which may illustrate how topographical features of Ti implant affect peri-implant angiogenesis. These results also suggest that the biological behaviors of HUVECs might be relative to the changed expression of intracellular Ca(2+).

This research provided a postoperative system for osteosarcoma which is seperated into two parts, Bone Patient and Bone Care. We focus on using smartphone features and proper interface design to facilitate self-monitoring, health analysis, and to make appointments. It achieves the effects of shared decision making (SDM). During the two weeks of research, we achieved satisfied with 4.03 ± 0.67 TAM score.