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The airway epithelium lining the luminal surface of the respiratory tract creates a protective barrier that ensures maintenance of tissue homeostasis and prevention of respiratory diseases. The airway epithelium, unfortunately, is frequently injured by inhaled toxic materials, trauma, or medical procedures. Substantial or repeated airway epithelial injury can lead to dysregulated intrinsic repair pathways and aberrant tissue remodeling that can lead to dysfunctional airway epithelium. While disruption in the epithelial integrity is directly linked to degraded epithelial barrier function, the correlation between the structure and function of the airway epithelium remains elusive. In this study, we quantified the impact of acutely induced airway epithelium injury on disruption of the epithelial barrier functions. By monitoring alternation of the flow motions and tissue bioimpedance at local injury site, degradation of the epithelial functions, including mucociliary clearance and tight/adherens junction formation, were accurately determined with a high spatiotemporal resolution. Computational models that can simulate and predict the disruption of the mucociliary flow and airway tissue bioimpedance have been generated to assist interpretation of the experimental results. Collectively, findings of this study advance our knowledge of the structure–function relationships of the airway epithelium that can promote development of efficient and accurate diagnosis of airway tissue injury. 

Abstract Ionizable lipid nanoparticles (LNPs) are pivotal in combating COVID‐19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid‐based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65 Hz) is utilized to prompt the LNP‐mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA, and increase the transfection efficiency of mRNA. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to mitochondrial membrane potential and Golgi apparatus integrity. Thus, this work presents a user‐friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, this work can be potentially utilized in both research and clinical fields to facilitate LNP‐based delivery by enabling more effective release of LNP‐encapsulated cargos from endosomes. 

Abstract Pulmonary air leak is the most common complication of lung surgery, contributing to post‐operative morbidity in up to 60% of patients; yet, there is no reliable treatment. Available surgical sealants do not match the demanding deformation mechanics of lung tissue; and therefore, fail to seal air leak. To address this therapeutic gap, a sealant with structural and mechanical similarity to subpleural lung is designed, developed, and systematically evaluated. This “lung‐mimetic” sealant is a hydrofoam material that has alveolar‐like porous ultrastructure, lung‐like viscoelastic properties (adhesive, compressive, tensile), and lung extracellular matrix‐derived signals (matrikines) to support tissue repair. In biocompatibility testing, the lung‐mimetic sealant shows minimal cytotoxicity and immunogenicity in vitro. Human primary monocytes exposed to sealant matrikines in vitro upregulate key genes (MARCO, PDGFB, VEGF) known to correlate with pleural wound healing and tissue repair in vivo. In rat and swine models of pulmonary air leak, this lung‐mimetic sealant rapidly seals air leak and restores baseline lung mechanics. Altogether, these data indicate that the lung‐mimetic sealant can effectively seal pulmonary air leak and promote a favorable cellular response in vitro.