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Surfactant replacement therapy is crucial in managing neonatal respiratory distress syndrome (RDS). Currently licensed clinical surfactants in the United States and Europe, including Survanta, Infasurf, Curosurf, and Alveofact, are all derived from bovine or porcine sources. We conducted a comprehensive examination of the biophysical properties of these four clinical surfactant preparations under physiologically relevant conditions, using constrained drop surfactometry (CDS). The assessed biophysical properties included the adsorption rate, quasi-static and dynamic surface activity, resistance to surfactant inhibition by meconium, and the morphology of the adsorbed surfactant films. This comparative study unveiled distinct in vitro biophysical properties of these clinical surfactants and revealed correlations between their chemical composition, lateral film structure, and biophysical functionality. Notably, at 1 mg/mL, Survanta exhibited a significantly lower adsorption rate compared with the other preparations at the same surfactant concentration. At 10 mg/mL, Infasurf, Curosurf, and Survanta all demonstrated excellent dynamic surface activity, whereas Alveofact exhibited the poorest quasi-static and dynamic surface activity. The suboptimal surface activity of Alveofact is found to be correlated with its unique monolayer-predominant morphology, in contrast to other surfactants forming multilayers. Curosurf, in particular, showcased superior resistance to biophysical inhibition by meconium compared with other preparations. Understanding the diverse biophysical behaviors of clinical surfactants provides crucial insights for precision and personalized design in treating RDS and other respiratory conditions. The findings from this study contribute valuable perspectives for the development of more efficacious and fully synthetic surfactant preparations. NEW & NOTEWORTHY: A thorough investigation into the biophysical properties of four animal-derived clinical surfactant preparations was conducted through constrained drop surfactometry under physiologically relevant conditions. This comparative study unveiled unique in vitro biophysical characteristics among these clinical surfactants, establishing correlations between their chemical composition, lateral film structure, and biophysical functionality. The acquired knowledge offers essential insights for the precise and personalized design of clinical surfactant for the treatment of respiratory distress syndrome and other respiratory conditions. [ABSTRACT FROM AUTHOR]

Graphene oxide (GO) is increasingly used in biomedical applications because it possesses not only the unique properties of graphene including large surface area and flexibility but also hydrophilicity and dispersibility in aqueous solutions. However, there are conflicting results on its biocompatibility and biosafety partially due to large variations in physicochemical properties of GO, and the role of these properties including lateral size in the biological or toxicological effects of GO is still unclear. In this study, we focused on the role of lateral size by preparing a panel of GO samples with differential lateral sizes using the same starting material. We found that, in comparison to its smaller counterpart, larger GO showed a stronger adsorption onto the plasma membrane with less phagocytosis, which elicited more robust interaction with toll-like receptors and more potent activation of NF-κB pathways. By contrast, smaller GO sheets were more likely taken up by cells. As a result, larger GO promoted greater M1 polarization, associated with enhanced production of inflammatory cytokines and recruitment of immune cells. The in vitro results correlated well with local and systemic inflammatory responses after GO administration into the abdominal cavity, lung, or bloodstream through the tail vein. Together, our study delineated the size-dependent M1 induction of macrophages and pro-inflammatory responses of GO in vitro and in vivo. Our data also unearthed the detailed mechanism underlying these effects: a size-dependent interaction between GO and the plasma membrane.

Pulmonary surfactant is a critical component of lung function in healthy individuals. It functions in part by lowering surface tension in the alveoli, thereby allowing for breathing with minimal effort. The prevailing thinking is that low surface tension is attained by a compression-driven squeeze-out of unsaturated phospholipids during exhalation, forming a film enriched in saturated phospholipids that achieves surface tensions close to zero. A thorough review of past and recent literature suggests that the compression-driven squeeze-out mechanism may be erroneous. Here, we posit that a surfactant film enriched in saturated lipids is formed shortly after birth by an adsorption-driven sorting process and that its composition does not change during normal breathing. We provide biophysical evidence for the rapid formation of an enriched film at high surfactant concentrations, facilitated by adsorption structures containing hydrophobic surfactant proteins. We examine biophysical evidence for and against the compression-driven squeeze-out mechanism and propose a new model for surfactant function. The proposed model is tested against existing physiological and pathophysiological evidence in neonatal and adult lungs, leading to ideas for biophysical research, that should be addressed to establish the physiological relevance of this new perspective on the function of the mighty thin film that surfactant provides. [ABSTRACT FROM AUTHOR]

Introduction The acute respiratory distress syndrome (ARDS) is characterized by severe lung dysfunction defined by a decrease in the partial pressure of arterial of [O.sub.2] (P[O.sub.2]) to the fractional inspired [...], The acute respiratory distress syndrome (ARDS) is characterized by arterial hypoxemia accompanied by severe inflammation and alterations to the pulmonary surfactant system. Published data has demonstrated a protective effect of matrix metalloproteinase-3 (Mmp3) deficiency against the inflammatory response associated with ARDS; however, the effect of Mmp3 on physiologic parameters and alterations to surfactant have not been previously studied. It was hypothesized that Mmp3 deficient ([Mmp3.sup.-/-]) mice would be protected against lung dysfunction associated with ARDS and maintain a functional pulmonary surfactant system. Wild type (WT) and [Mmp3.sup.-/-] mice were subjected to acid-aspiration followed by mechanical ventilation. [Mmp3.sup.-/-] mice maintained higher arterial oxygenation compared with WT mice at the completion of ventilation. Significant increase in functional large aggregate surfactant forms were observed in [Mmp3.sup.-/-] mice compared with WT mice. These findings further support a role of Mmp3 as an attractive therapeutic target for drug development in the setting of ARDS. Key words: matrix metalloproteinase-3, acute respiratory distress syndrome, acute lung injury, pulmonary surfactant, mechanical ventilation, acid aspiration, hypoxemia. Le syndrome de detresse respiratoire aigue (ARDS) est caracterise par une hypoxemie arterielle accompagnee d'une inflammation et d'alterations graves au niveau du systeme du surfactant pulmonaire. Les donnees publiees montrent que le deficit en metalloproteinase matricielle-3 (Mmp3) a un effet protecteur contre la reaction inflammatoire associee a l'ARDS. Toutefois, l'effet de la Mmp3 sur les parametres physiologiques et les alterations du surfactant n'a pas encore ete etudie. Nous avons pose l'hypothese selon laquelle les souris presentant un deficit en Mmp3 ([Mmp3.sup.-/-]) seraient protegees contre le dysfonctionnement pulmonaire associe a l'ARDS et maintiendraient fonctionnel le systeme du surfactant pulmonaire. A cette fin, nous avons soumis des souris de types sauvage (WT) et [Mmp3.sup.-/-] a l'aspiration d'acide suivie d'une ventilation mecanique. Nous avons observe le maintien d'une oxygenation arterielle plus elevee dans le groupe [Mmp3.sup.-/-] que dans le groupe WT apres la ventilation. En outre, nous avons observe une augmentation nettement plus importante du surfactant sous forme d'agregats de grande taille dans le groupe [Mmp3.sup.-/-] que dans le groupe WT. En definitive, ces resultats contribuent a appuyer le role de la Mmp3 comme cible therapeutique interessante pour le developpement de medicaments dans le cadre de l'ARDS. [Traduit par la Redaction] Mots-cles: metalloproteinase matricielle-3, syndrome de detresse respiratoire aigue, lesion pulmonaire aigue, surfactant pulmonaire, ventilation mecanique, aspiration d'acide, hypoxemie.