Revealing the Structural Intricacies of Biomembrane-Interfaced Emulsions with Small- and Ultra-Small-Angle Neutron Scattering.

Utilizing cell membranes from diverse cell types for biointerfacing has demonstrated significant advantages in enhancing colloidal stability and incorporating biological properties, tailored specifically for various biomedical applications. However, the structures of these materials, particularly emulsions interfaced with red blood cell (RBC) or platelet (PLT) membranes, remain an underexplored area. This study systematically employs small- and ultra-small-angle neutron scattering (SANS and USANS) with contrast variation to investigate the structure of emulsions containing perfluorohexane within RBC (RBC/PFH) and PLT membranes (PLT/PFH). The findings reveal that the scattering length density of RBC and PLT membranes is 1.5 × 10-6 Å-2, similar to 30% (w/w) deuterium oxide. Using this solvent as a cell membrane-matching medium, estimated droplet diameters are 770 nm (RBC/PFH) and 1.5 µm (PLT/PFH), based on polydispersed sphere model fitting. Intriguingly, calculated patterns and invariant analysis reveal native droplet architectures featuring entirely liquid PFH cores, differing significantly from the observed bubble-droplet core system in electron microscopy. This highlights the advantage of SANS and USANS in differentiating genuine colloidal structures in complex dispersions. In summary, this work underscores the pivotal role of SANS and USANS in characterizing biointerfaced colloids and in uncovering novel colloidal structures with significant potential for biomedical applications and clinical translation.

Iatrogenic macular hole following PFCL injection: Implications of retinal dimpling as an intraoperative indicator.

Background: Perfluorocarbon liquid (PFCL) revolutionized retinal detachment (RD) management in vitreoretinal surgery but introduced unique risks. Complications like subretinal migration are documented, yet specific warnings for macular hole (MH) formation during PFCL injection are lacking. Case presentation: In a rhegmatogenous RD case, a localized retinal dimpling during PFCL jet stream injection, preceded subsequent complications-an immediate MH and subretinal PFCL migration. Subsequently, an internal limiting membrane peeling with PFCL mobilization was performed.successfully managed the situation. Post-surgery, optical coherence tomography (OCT) confirmed a closed MH with improved vision. Conclusion: This case report not only sheds light on a previously undocumented complication associated with PFCL injection but also underscores the critical need for adherence to proper injection technique to minimize traumatic effects. Understanding the mechanism underlying this complication and implementing corrective measures are essential for enhancing intraoperative strategies and minimizing adverse outcomes in retinal surgeries involving PFCL.

Light-induced manipulation of ultra-low surface tension droplets on stable quasi-liquid surfaces.

HYPOTHESIS: Perfluorocarbon is commonly used as a coolant, chemical reaction carrier solvent, medical anti-hypoxic agents and blood substitutes. The realization of non-contact complex manipulation of perfluorocarbon liquids is urgently needed in human life and industrial production. However, most liquid-repellent interfaces are ineffective for the transport of ultra-low surface tension perfluorocarbon liquids, and struggle to maintain good durability due to unstable air or oil cushions in the surface. Therefore, preparing surfaces for stable non-contact complex manipulation of ultra-low surface tension droplets remains a challenge. EXPERIMENTS: In this paper, a novel solution, a photothermal responsive droplet manipulation surface based on polydimethylsiloxane brushes, has been reported. On this surface, droplets with different surface tensions (as low as 10 mN/m) can be efficiently manipulated through induced near-infrared light. Notably, this surface maintains its effectiveness after exposure to extreme anthropogenic conditions. FINDINGS: The interface effect between perfluorocarbon droplets and polydimethylsiloxane brushes by near-infrared light-induced was investigated in detail. In addition, ultra-low surface tension droplets demonstrate the ability to transport solid particles. The conductive droplets exhibit sophisticated manipulation realizing the controlled switching of smart circuits. This research opens up new possibilities for advancing the capabilities and adaptability of ultralow surface tension droplets in a range of applications.

Decoupling Fluorous Protein Coatings Yield Heat-Stable and Intrinsically Sterile Bioformulations.

Thermal inactivation is a major bottleneck to the scalable production, storage, and transportation of protein-based reagents and therapies. Failures in temperature control both compromise protein bioactivity and increase the risk of microorganismal contamination. Herein, we report the rational design of fluorochemical additives that promiscuously bind to and coat the surfaces of proteins to enable their stable dispersion within fluorous solvents. By replacing traditional aqueous liquids with fluorinated media, this strategy conformationally rigidifies proteins to preserve their structure and function at extreme temperatures (≥90 °C). We show that fluorous protein formulations resist contamination by bacterial, fungal, and viral pathogens, which require aqueous environments for survival, and display equivalent serum bioavailability to standard saline samples in animal models. Importantly, by designing dispersants that decouple from the protein surface in physiologic solutions, we deliver a fluorochemical formulation that does not alter the pharmacologic function or safety profile of the functionalized protein in vivo. As a result, this nonaqueous protein storage paradigm is poised to open technological opportunities in the design of shelf-stable protein reagents and biopharmaceuticals.

Cryo-Fluorescence Tomography as a Tool for Visualizing Whole-Body Inflammation Using Perfluorocarbon Nanoemulsion Tracers.

PURPOSE: We explore the use of intravenously delivered fluorescent perfluorocarbon (PFC) nanoemulsion tracers and multi-spectral cryo-fluorescence tomography (CFT) for whole-body tracer imaging in murine inflammation models. CFT is an emerging technique that provides high-resolution, three-dimensional mapping of probe localization in intact animals and tissue samples, enabling unbiased validation of probe biodistribution and minimizes reliance on laborious histological methods employing discrete tissue panels, where disseminated populations of PFC-labeled cells may be overlooked. This methodology can be used to streamline the development of new generations of non-invasive, cellular-molecular imaging probes for in vivo imaging. PROCEDURES: Mixtures of nanoemulsions with different fluorescent emission wavelengths were administered intravenously to naïve mice and models of acute inflammation, colitis, and solid tumor. Mice were euthanized 24 h post-injection, frozen en bloc, and imaged at high resolution (~ 50 µm voxels) using CFT at multiple wavelengths. RESULTS: PFC nanoemulsions were visualized using CFT within tissues of the reticuloendothelial system and inflammatory lesions, consistent with immune cell (macrophage) labeling, as previously reported in in vivo magnetic resonance and nuclear imaging studies. The CFT signals show pronounced differences among fluorescence wavelengths and tissues, presumably due to autofluorescence, differential fluorescence quenching, and scattering of incident and emitted light. CONCLUSIONS: CFT is an effective and complementary methodology to in vivo imaging for validating PFC nanoemulsion biodistribution at high spatial localization, bridging the resolution gap between in vivo imaging and histology.

Targeted drug release from stable and safe ultrasound-sensitive nanocarriers.

Targeted delivery of medication has the promise of increasing the effectiveness and safety of current systemic drug treatments. Focused ultrasound is emerging as noninvasive and practical energy for targeted drug release. However, it has yet to be determined which nanocarriers and ultrasound parameters can provide both effective and safe release. Perfluorocarbon nanodroplets have the potential to achieve these goals, but current approaches have either been effective or safe, but not both. We found that nanocarriers with highly stable perfluorocarbon cores mediate effective drug release so long as they are activated by ultrasound of sufficiently low frequency. We demonstrate a favorable safety profile of this formulation in a non-human primate. To facilitate translation of this approach into humans, we provide an optimized method for manufacturing the nanocarriers. This study provides a recipe and release parameters for effective and safe drug release from nanoparticle carriers in the body part specified by focused ultrasonic waves.

Laser-activated perfluorocarbon nanodroplets for intracerebral delivery and imaging via blood-brain barrier opening and contrast-enhanced imaging.

BACKGROUND: Ultrasound and photoacoustic (US/PA) imaging is a promising tool for in vivo visualization and assessment of drug delivery. However, the acoustic properties of the skull limit the practical application of US/PA imaging in the brain. To address the challenges in targeted drug delivery to the brain and transcranial US/PA imaging, we introduce and evaluate an intracerebral delivery and imaging strategy based on the use of laser-activated perfluorocarbon nanodroplets (PFCnDs). METHODS: Two specialized PFCnDs were developed to facilitate blood‒brain barrier (BBB) opening and contrast-enhanced US/PA imaging. In mice, PFCnDs were delivered to brain tissue via PFCnD-induced BBB opening to the right side of the brain. In vivo, transcranial US/PA imaging was performed to evaluate the utility of PFCnDs for contrast-enhanced imaging through the skull. Ex vivo, volumetric US/PA imaging was used to characterize the spatial distribution of PFCnDs that entered brain tissue. Immunohistochemical analysis was performed to confirm the spatial extent of BBB opening and the accuracy of the imaging results. RESULTS: In vivo, transcranial US/PA imaging revealed localized photoacoustic (PA) contrast associated with delivered PFCnDs. In addition, contrast-enhanced ultrasound (CEUS) imaging confirmed the presence of nanodroplets within the same area. Ex vivo, volumetric US/PA imaging revealed PA contrast localized to the area of the brain where PFCnD-induced BBB opening had been performed. Immunohistochemical analysis revealed that the spatial distribution of immunoglobulin (IgG) extravasation into the brain closely matched the imaging results. CONCLUSIONS: Using our intracerebral delivery and imaging strategy, PFCnDs were successfully delivered to a targeted area of the brain, and they enabled contrast-enhanced US/PA imaging through the skull. Ex vivo imaging, and immunohistochemistry confirmed the accuracy and precision of the approach.

Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation.

Lipid-coated perfluorocarbon nanodroplets (lp-NDs) hold great promise in bio-medicine as vehicles for drug delivery, molecular imaging and vaccine agents. However, their clinical utility is restricted by limited targeted accumulation, attributed to the innate immune system (IIS), which acts as the initial defense mechanism in humans. This study aimed to optimize lp-ND formulations to minimize non-specific clearance by the IIS. Ginsenosides (Gs), the principal components of Panax ginseng, possessing complement inhibition ability, structural similarity to cholesterol, and comparable fat solubility to phospholipids, were used as promising candidate IIS inhibitors. Two different types of ginsenoside-based lp-NDs (Gs lp-NDs) were created, and their efficacy in reducing IIS recognition was examined. The Gs lp-NDs were observed to inhibit the adsorption of C3 in the protein corona (PC) and the generation of SC5b-9. Adding Gs to lp-NDs reduced complement adsorption and phagocytosis, resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs. These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants, potentially reducing non-specific clearance by the IIS and improving lifespan.

Oxygen Self-Supplied Perfluorocarbon-Modified Micelles for Enhanced Cancer Photodynamic Therapy and Ferroptosis.

Photodynamic therapy (PDT) and ferroptosis show significant potential in tumor treatment. However, their therapeutic efficacy is often hindered by the oxygen-deficient tumor microenvironment and the challenges associated with efficient intracellular drug delivery into tumor cells. Toward this end, this work synthesized perfluorocarbon (PFC)-modified Pluronic F127 (PFC-F127), and then exploits it as a carrier for codelivery of photosensitizer Chlorin e6 (Ce6) and the ferroptosis promoter sorafenib (Sor), yielding an oxygen self-supplying nanoplatform denoted as Ce6-Sor@PFC-F127. The PFCs on the surface of the micelle play a crucial role in efficiently solubilizing and delivering oxygen as well as increasing the hydrophobicity of the micelle surface, giving rise to enhanced endocytosis by cancer cells. The incorporation of an oxygen-carrying moiety into the micelles enhances the therapeutic impact of PDT and ferroptosis, leading to amplified endocytosis and cytotoxicity of tumor cells. Hypotonic saline technology was developed to enhance the cargo encapsulation efficiency. Notably, in a murine tumor model, Ce6-Sor@PFC-F127 effectively inhibited tumor growth through the combined use of oxygen-enhanced PDT and ferroptosis. Taken together, this work underscores the promising potential of Ce6-Sor@PFC-F127 as a multifunctional therapeutic nanoplatform for the codelivery of multiple cargos such as oxygen, photosensitizers, and ferroptosis inducers.

In Vitro and In Vivo Behavioral Evaluation of Condensed Lipid-Coated Perfluorocarbon Nanodroplets.

OBJECTIVE: Phase-shift contrast agents consist of a liquid perfluorocarbon core that can be vaporized by ultrasound to generate echogenic contrast with excellent spatiotemporal control. The purpose of the present work was to evaluate the in vitro and in vivo behavior of condensed lipid-shelled nanodroplets (NDs) using different analytical procedures. METHODS: Perfluorobutane NDs were prepared by condensation of precursor fluorescently labeled lipid-shelled microbubbles (MBs) and were characterized in terms of size distribution, gas core content and in vitro stability in blood, as well as for their acoustic vaporization behavior using a custom-made setup. In particular, the in vivo behavior of the NDs was thoroughly investigated after intravenous bolus injection in rats. To this end, we report, for the first time, the efficient use of three complementary detection procedures to assess the in vivo persistence of NDs: (i) ultrasound contrast imaging of vaporized NDs, (ii) gas chromatography-mass spectrometry to determine the perfluorobutane core content and (iii) fluorescence intensity measurement in the collected blood samples. RESULTS: The Coulter Counter Multisizer results confirmed the size distribution shift post-condensation. Furthermore, similar PFB concentrations from MB and ND suspensions were obtained, indicating an exceptionally low rate of MB breakage and spontaneous nanodroplet vaporization. As expected, these nanoscale droplets have longer circulation times compared with clinically approved MBs, and only slight variations in half-life were observed between the three monitoring procedures. Finally, echogenic signal observed in focal areas of the liver and spleen after vaporization was confirmed by accumulation of fluorescent nanodroplets in these organs. CONCLUSION: These results further contribute to our understanding of both the in vitro and in vivo behavior of sono-responsive nanodroplets, which is key to enabling efficient clinical translation.

Hemostatic and Ultrasound-Controlled Bactericidal Silk Fibroin Hydrogel via Integrating a Perfluorocarbon Nanoemulsion.

Excessive blood loss and infections are the prominent risks accounting for mortality and disability associated with acute wounds. Consequently, wound dressings should encompass adequate adhesive, hemostatic, and bactericidal attributes, yet their development remains challenging. This investigation presented the benefits of incorporating a perfluorocarbon nanoemulsion (PPP NE) into a silk-fibroin (SF)-based hydrogel. By stimulating the ß-sheet conformation of the SF chains, PPP NEs drastically shortened the gelation time while augmenting the elasticity, mechanical stability, and viscosity of the hydrogel. Furthermore, the integration of PPP NEs improved hemostatic competence by boosting the affinity between cells and biomacromolecules. It also endowed the hydrogel with ultrasound-controlled bactericidal ability through the inducement of inner cavitation by perfluorocarbon and reactive oxygen species (ROS) generated by the sonosensitizer protoporphyrin. Ultimately, we employed a laparotomy bleeding model and a Staphylococcus aureus-infected trauma wound to demonstrate the first-aid efficacy. Thus, our research suggested an emulsion-incorporating strategy for managing emergency wounds.

Why Perfluorocarbon nanoparticles encounter bottlenecks in clinical translation despite promising oxygen carriers?

Artificial Oxygen Carriers (AOCs) have emerged as ground-breaking biomedical solutions, showcasing tremendous potential for enhancing human health and saving lives. Perfluorocarbon (PFC)-based AOCs, in particular, have garnered significant interest among researchers, leading to numerous clinical trials since the 1980 s. However, despite decades of exploration, the success rate has remained notably limited. This comprehensive review article delves into the landscape of clinical trials involving PFC compounds, shedding light on the challenges and factors contributing to the lack of clinical success with PFC nanoparticles till date. By scrutinizing the existing trials, the article aims to uncover the underlying issues like pharmacological side effects of the PFC and the nanomaterials used for the designing, complex formulation strategy and poor clinical trial designs of the formulation. More over each generation of the PFC formulation were discussed with details for their failure in the clinical trials limitations that block the path of PFC-based AOCs' full potential. Furthermore, the review emphasizes a forward-looking approach by outlining the future pathways and strategies essential for achieving success in clinical trials. AOCs require advanced yet biocompatible single-componentformulations. The new trend might be a novel drug delivery technique, like gel emulsion or reverse PFC emulsion with fluoro surfactants. Most importantly, well-planned clinical trials may end in a success story.

Investigation of Optimum Production Conditions and the Stability of ß-Cyclodextrin-Perfluorocarbon Nanocone Clusters for Histotripsy Applications.

Nanocone clusters (NCCs) have been developed as clusters with inclusion complexes of FDA-approved ß-cyclodextrin (ßCD) and perfluorocarbons (PFC) (i.e., perfluoropentane (PFP) and perfluorohexane (PFH)) and have shown promise in nanoparticle-mediated histotripsy (NMH) applications owing to their lowered cavitation threshold, ease of production, and fluorocarbon quantification. However, there is still a lack of information on the best conditions of the synthesis of NCCs as a product that can have a maximum determinable fluorocarbon content and maintain the stability of the NCC during synthesis and when used as histotripsy agents or exposed to physiological conditions. These concerns about the stability of the clusters and the best possible formulation are investigated in the current work. The cluster formation potential was tested taking into consideration the nature of both PFCs and ßCD by employing different synthesis conditions in terms of solution and environmental parameters such as concentration of solvent, stoichiometry between ßCD and PFCs, temperature, pH, solvent type, etc. The best route of synthesis was then translated into various batch sizes and investigated in terms of the PFC loading and yield. These studies revealed that preparing NCCs in double-distilled water in an ice bath at the optimized solution concentration gave the highest yields and optimal PFC loading, as determined from gas chromatography. Furthermore, the stability of the clusters with different stoichiometries was scrutinized in varying concentrations, mechanical disruption times, pH levels, and temperature conditions, showing effects on each cluster's particle size in dynamic light scattering, visualized in transmission electron microscopy, and cavitation behavior in agarose gel tissue phantoms. These studies revealed stable clusters for all formulations, with PFH-containing NCCs emerging to be the most stable in terms of their cluster size and bubble formation potential in histotripsy. Finally, the shelf life of these clusters was investigated using DLS, which revealed a stable cluster. In conclusion, NCCs have shown high stability in terms of both synthesis, which can be replicated in gram-level production, and the cluster itself, which can be exposed to harsher conditions and still form stable bubbles in histotripsy.

Repeatable Acoustic Vaporization of Coated Perfluorocarbon Bubbles for Micro-Actuation Inspired by Polypodium aureum.

Polypodium aureum, a fern, possesses a specialized spore-releasing mechanism like a catapult induced by the quick expansion of vaporized bubbles. This study introduces lipid-coated perfluorocarbon droplets to enable repeatable vaporization-condensation cycles, inspired by the repeatable vaporization of Polypodium aureum. Lipid-perfluorocarbon droplets have been considered not to exhibit repeatable oscillations due to bubble collapse of the low surface tension of lipid layers. However, a single lipid-dodecafluoropentane droplet with a diameter of 9.17 µm shows expansion-contraction oscillations over 4000 cycles by changing lipid composition and applying a low-power 1.7 MHz ultrasound to induce the partial vaporization of the droplets. The optimal combinations of shell composition, droplet fabrication, and acoustic conditions can minimize the damage on shell structure and promote a quick recovery of damaged shell layers. The highly expanding oscillatory microbubbles provide a new direction for fuel-free micro- or nanobots, as well as biomedical applications of contrast agents and drug delivery.

Novel perfluorocarbon-based oxygenation therapy alleviates Post-SAH hypoxic brain injury by inhibiting HIF-1α.

In comparison to other stroke types, subarachnoid hemorrhage (SAH) is characterized by an early age of onset and often results in poor prognosis. The inadequate blood flow at the site of the lesion leads to localized oxygen deprivation, increased level of hypoxia-inducible factor-1α (HIF-1α), and triggers inflammatory responses and oxidative stress, ultimately causing hypoxic brain damage. Despite the potential benefits of oxygen (O2) administration, there is currently a lack of efficient focal site O2 delivery following SAH. Conventional clinical O2 supply methods, such as transnasal oxygenation and hyperbaric oxygen therapy, do not show the ideal therapeutic effect in severe SAH patients. The perfluorocarbon oxygen carrier (PFOC) demonstrates efficacy in transporting O2 and responding to elevated levels of CO2 at the lesion site. Through cellular experiments, we determined that PFOC oxygenation serves as an effective therapeutic approach in inhibiting hypoxia. Furthermore, our animal experiments showed that PFOC oxygenation outperforms O2 breathing, leading to microglia phenotypic switching and the suppression of inflammatory response via the inhibition of HIF-1α. Therefore, as a new type of O2 therapy after SAH, PFOC oxygenation can effectively reduce hypoxic brain injury and improve neurological function.

Efficacy of the use of perfluorocarbon as a temporary tamponade agent in severe ocular trauma and/or complex retinopexy: a scoping review.

BACKGROUND: Perfluorocarbon (PFC)possesses unique chemical properties that favor the pigment epithelium's adhesion and allows the drainage of subretinal fluid through retinal holes present in retinal detachment cases. However, PFC as a temporary tamponade agent has been limited due to its high potential for toxicity. MAIN BODY: We conducted a scoping review regarding the use of PFC in vitreoretinal surgery as a temporary tamponade in subjects with severe ocular trauma or severe retinal detachment who received a therapeutic intervention (vitrectomy via posterior approach with the use of PFC as a temporary tamponade), compared to vitrectomy without the use of PFC as a temporary tamponade. Outcomes of interest were retinal reattachment, visual acuity (VA), postoperative complications and retinal toxicity. The search was performed in Medline, Medline In-Process & Other Non-Indexed Citations, Medline Daily Update, Embase databases. Reference lists from relevant review articles were also included. Two hundred thirty-eight studies were found, with no duplicate entries. In the first selection, 230 articles were eliminated; in the second selection, 6 additional articles were discarded. In total, 8 articles were obtained in this review. Two selected articles corresponded to animal studies and 6 to studies in humans. Regarding study design, 5 were case series, and 1 was a cohort study. CONCLUSION: PFC as a short-term tamponade had high rates of reapplication, improved VA, and the most frequent adverse effects were reversible after PFC withdrawal. Nonetheless, the quality of the studies was poor. Studies with more rigorous methodologies are needed to determine visual and structural outcomes and potential risks of PFC use as a temporary tamponade in vitreoretinal surgery.

Infiltrating Perfluorocarbon Nanoemulsion and Sensitizing Ultrasound Cavitation to Eradicate Biofilms.

Developing strategies for the treatment of bacterial biofilms is challenging due to their complex and resilient structure, low permeability to therapeutics, and ability to protect resident pathogens. Herein, we demonstrate that a polylysine-stabilized perfluorocarbon nanoemulsion is favored for penetrating biofilms and sensitizing the cavitation effect of low-intensity ultrasound, resulting in the dispersal of extracellular polymeric substances and killing of the protected cells. Through experiments, we observed a complete penetration of the nanoemulsion in a 40 µm Pseudomonas aeruginosa biofilm and demonstrated that it was induced by the fluidic perfluorocarbon, possibly attributing to its low surface tension. Furthermore, we presented an almost complete antibiofilm effect with a low-intensity ultrasound (1 MHz, 0.75 W/cm2, 5 min) in diverse cases, including cultured biofilms, colonized urinary catheters, and chronic wounds. During the treatment process, the perfluorocarbon phase enhanced the number and imploding energy of ultrasound cavities, thoroughly divided the biofilm structure, prevented biofilm self-healing, and sterilized the resident pathogens. Thus, the penetration and sensitization of the nanoemulsion might serve as a facile and potent strategy for eradicating biofilms in various applications.

A minimum specification dataset for liquid ocular endotamponades: recommendations by a European expert panel.

PURPOSE: To propose a minimum specification dataset to characterize liquid ocular endotamponades (OEs), namely silicone oil (SO), heavy SO (HSO), perfluorodecalin (PFD), and perfluoro-octane (PFO), in terms of physicochemical properties, purity and available evidence of safety, in line with ISO16672:2020. METHODS: An evidence-based consensus using the expert panel technique was conducted. Two facilitators led a committee of 11 European experts. Facilitators prepared a dataset for each compound including the list of specifications relevant for the safety, identified by the group members on the basis of expertise and a comprehensive literature review. Each item was ranked by each member using a 9-point scale from 1 "absolutely to not include" to 9 "absolutely to include" in two rounds followed by discussion. Only items reaching consensus (score ≥ 7 from ≥ 75% of members) were included in the final datasets. RESULTS: For all OEs, consensus was reached to include manufacturer, density, refractive index, chemical composition, dynamic viscosity, interfacial and surface tension, endotoxins, in vitro cytotoxicity assessment, and any evidence from ex vivo and/or in vivo tests for safety assessment. Additional specifications were added for SO (molecular weight distribution, content of oligosiloxanes with MW ≤ 1000 g/mol, spectral transmittance) and PFD/PFO (% of pure PFD/PFO in the final product, vapor pressure, chemical analyses performed for safety assessment). CONCLUSION: The proposed evidence-based minimum specification datasets for SO, HSO, PFD, and PFO have the potential to provide surgeons and health service purchasers with an easily available overview of the most relevant information for the safety assessment of OEs.

Reduction of cell surface attachment in experimental hydrocephalus using a novel ventricular catheter with modified tethered liquid perfluorocarbon.

OBJECTIVE: Ventriculoperitoneal shunting, the most common treatment for the neurological disorder hydrocephalus, has a failure rate of up to 98% within 10 years of placement, mainly because of proximal obstruction of the ventricular catheter (VC). The authors developed a new VC design modified with tethered liquid perfluorocarbon (TLP) and tested it in a porcine model of hydrocephalus. In this study, they aimed to determine if their TLP VC design reduced cell surface attachment and consequent shunt obstruction in the pig model. METHODS: TLP VCs were designed to reduce drainage hole obstruction using modified TLP and slightly enlarged draining holes, but their number and placement remained very similar to standard VCs. First, the authors tested the device in nonhydrocephalic rats to assess biocompatibility. After confirming safety, they implanted the VCs in hydrocephalic pigs. Hydrocephalus was induced by intracisternal kaolin injections in 30-day-old domestic juvenile pigs. Surgical implantation of the ventriculoperitoneal shunt (clinical control or TLP) was performed 10-14 days postinduction and maintained up to 30 days posttreatment. MRI was performed to measure ventricular volume before treatment and 10 and 30 days after treatment. Histological and immunohistochemical analyses of brain tissue and explanted VCs, intracranial pressure measurement, and clinical scoring were performed when the animals were euthanized. RESULTS: TLP VCs showed a similar surgical feel, kink resistance, and stiffness to control VCs. In rats (biocompatibility assessment), TLP VCs did not show brain inflammatory reactions after 30 or 60 days of implantation. In pigs, TLP VCs demonstrated increased survival time, improved clinical outcome scores, and significantly reduced total attached cells on the VCs compared with standard clinical control VCs. TLP VCs exhibited similar, but not worse, results related to ventriculomegaly, intracranial pressure, and the local tissue response around the cortical shunt track in pigs. CONCLUSIONS: TLP VCs may be a strong candidate to reduce proximal VC obstruction and improve hydrocephalus treatment.

Phase-Change Based Oxygen Carriers Improve Acute Cerebral Hypoxia.

Stroke is the second leading cause of death worldwide, and hypoxia is a major crisis of the brain after stroke. Therefore, providing oxygen to the brain microenvironment can effectively protect neurons from damage caused by cerebral hypoxia. However, there is a lack of timely and effective means of oxygen delivery clinically to the brain for acute cerebral hypoxia. Here, a phase-change based nano oxygen carrier is reported, which can undergo a phase change in response to increasing temperature in the brain, leading to oxygen release. The nano oxygen carrier demonstrate intracerebral oxygen delivery capacity and is able to release oxygen in the hypoxic and inflammatory region of the brain. In the acute ischemic stroke mouse model, the nano oxygen carrier can effectively reduce the area of cerebral infarction and decrease the level of inflammation triggered by cerebral hypoxia. By taking advantage of the increase in temperature during cerebral hypoxia, phase-change oxygen carrier proposes a new intracerebral oxygen delivery strategy for reducing acute cerebral hypoxia.