Phototherapy and multimodal imaging of cancers based on perfluorocarbon nanomaterials.

Phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), possesses unique characteristics of non-invasiveness and minimal side effects in cancer treatment, compared with conventional therapies. However, the ubiquitous tumor hypoxia microenvironments could severely reduce the efficacy of oxygen-consuming phototherapies. Perfluorocarbon (PFC) nanomaterials have shown great practical value in carrying and transporting oxygen, which makes them promising agents to overcome tumor hypoxia and extend reactive oxygen species (ROS) lifetime to improve the efficacy of phototherapy. In this review, we summarize the latest advances in PFC-based PDT and PTT, and combined multimodal imaging technologies in various cancer types, aiming to facilitate their application-oriented clinical translation in the future.

Polypyrrole-coated phase-change liquid perfluorocarbon nanoparticles for the visualized photothermal-chemotherapy of breast cancer.

A theranostic nanoplatform (DTX/PFH@PPy-FA) for multi-modal imaging-guided photothermal-chemotherapy has been constructed. Lipid-perfluorohexane (PFH) nanodroplet loaded with docetaxel (DTX) was coated with a polypyrrole (PPy) shell. Then the folic acid (FA) molecule with active tumor-targeting function was modified on the surface of PPy shell. Due to the good photothermal conversion performance, PPy shell can raise the temperature under the near infrared laser irradiation, which not only produces photothermal effect to kill tumor cells, but also promotes liquid-gas phase change of PFH, and produces ultrasound imaging effect. The results of photothermal experiment and imaging experiment confirmed that the obtained DTX/PFH@PPy-FA possessed good photothermal, photoacoustic imaging and ultrasound imaging effects in vitro and in vivo. The results of in vitro cell experiments showed that DTX/PFH@PPy-FA had a active targeting ability to tumor cells, and its photothermal-chemotherapy synergistically inhibited the proliferation of tumor cells. In vivo study on 4T1-bearing BALB/c mice indicated that the photothermal-chemotherapy of DTX/PFH@PPy-FA not only effectively inhibited the growth of 4T1 breast cancer, but also inhibited lung metastasis. This multifunctional nanoparticle is expected to become a new nanoplatform for the visualized photothermal-chemotherapy of cancer. STATEMENT OF SIGNIFICANCE: In this work, we presented a multi-modal imaging-guided photothermal-chemotherapy theranostic nanoplatform (DTX/PFH@PPy-FA) for visualized treatment of breast cancer. The docetaxel (DTX) loaded perfluorohexane (PFH) nanodroplets (DTX/PFH@SPC) were firstly prepared and then coated with polypyrrole shell (PPy). Then, PEGylated folic acid was covalently modified to obtain the folate-targeted multifunctional nanoparticle (DTX/PFH@PPy-FA). Due to the good photothermal conversion performance, PPy shell can raise the temperature under the near infrared laser irradiation, which not only produces photothermal effect to kill tumor cells, but also promotes liquid-gas phase change of PFH, and produces good ultrasound imaging effect. The PPy shell also imparts photoacoustic imaging characteristics to the nanoparticles. Experimental results show that our prepared DTX/PFH@PPy-FA possesses folic acid-mediated tumor targeting ability, ultrasound and photoacoustic imaging, and photothermal-chemotherapy synergistic effect. This multi-functional nanoparticle is expected to become a new platform for the visualized photothermal-chemotherapy of breast cancer.

Effect of vaporized perfluorocarbon on oxidative stress during the cold ischemia phase of lung graft preservation.

Liquid perfluorocarbon (PFC) instillation has been studied experimentally as an adjuvant therapy in the preservation of lung grafts during cold ischemia. The objective of this study was to evaluate whether vaporized PFC is also protective of lung grafts at different cold ischemia times. We performed histological analysis of and measured oxidative stress in the lungs of animals that received only preservation solution with low-potassium dextran (LPD) or vaporized PFC together with LPD. We conclude that vaporized PFC reduces the production of free radicals and the number of pulmonary structural changes resulting from cold ischemia.

Effect of vaporized perfluorocarbon on oxidative stress during the cold ischemia phase of lung graft preservation / Efeito do perfluorocarbono vaporizado sobre o estresse oxidativo no período de isquemia fria durante a preservação pulmonar

ABSTRACT Liquid perfluorocarbon (PFC) instillation has been studied experimentally as an adjuvant therapy in the preservation of lung grafts during cold ischemia. The objective of this study was to evaluate whether vaporized PFC is also protective of lung grafts at different cold ischemia times. We performed histological analysis of and measured oxidative stress in the lungs of animals that received only preservation solution with low-potassium dextran (LPD) or vaporized PFC together with LPD. We conclude that vaporized PFC reduces the production of free radicals and the number of pulmonary structural changes resulting from cold ischemia.

RESUMO O perfluorocarbono (PFC) líquido tem sido estudado experimentalmente como uma substância adjuvante na preservação de enxertos pulmonares durante o período de isquemia fria. O objetivo deste estudo foi avaliar se o PFC vaporizado (e não instilado) também atuaria como protetor de enxertos pulmonares em diferentes tempos de isquemia fria. Realizamos análise histológica e dosamos o estresse oxidativo em pulmões de animais que receberam somente uma solução de preservação com low-potassium dextran (LPD, dextrana com baixa concentração de potássio) ou PFC vaporizado associado a LPD. Concluímos que o PFC vaporizado reduziu a produção de radicais livres e provocou menor número de alterações estruturais pulmonares decorrentes do período de isquemia fria que o uso de LPD isoladamente.

PA/US dual-modality imaging to guide VEGFR-2 targeted photothermal therapy using ZnPc-/PFH-loaded polymeric nanoparticles.

Angiogenesis is a common pathological characteristic of many solid tumors and vulnerable atherosclerotic plaques. Photothermal therapy (PTT) is a promising method to reduce neovascularization. To increase the targeting ability and efficiency of PTT, a novel polymeric nanosystem that encapsulates phthalocyanine zinc (ZnPc) and perfluorohexane (PFH) was developed to target the new blood vessels of breast tumors. After being conjugated to the anti-VEGFR-2 antibody, the polymeric nanoparticles (NPs) targeted vascular endothelial cells efficiently. The photosensitizer (PS) in the NPs could convert laser energy into heat, generating local high temperatures to kill the surrounding cells under laser irradiation. In addition, the liquid-gas phase transition of PFH was induced, and an enhanced ultrasound (US) and photoacoustic (PA) image could be obtained. US/PA imaging enables visualization of the location of NPs, and laser irradiation position can be guided to the optimal location, resulting in fewer side effects than those from traditional treatments with a high targeting ability and an efficient synergistic effect from the PTT.

Protecting the ischaemic penumbra as an adjunct to thrombectomy for acute stroke.

After ischaemic stroke, brain damage can be curtailed by rescuing the 'ischaemic penumbra' - that is, the severely hypoperfused, at-risk but not yet infarcted tissue. Current evidence-based treatments involve restoration of blood flow so as to salvage the penumbra before it evolves into irreversibly damaged tissue, termed the 'core'. Intravenous thrombolysis (IVT) can salvage the penumbra if given within 4.5 h after stroke onset; however, the early recanalization rate is only ~30%. Direct removal of the occluding clot by mechanical thrombectomy considerably improves outcomes over IVT alone, but despite early recanalization in > 80% of cases, ~50% of patients who receive this treatment do not enjoy functional independence, usually because the core is already too large at the time of recanalization. Novel therapies aiming to 'freeze' the penumbra - that is, prevent core growth until recanalization is complete - hold potential as adjuncts to mechanical thrombectomy. This Review focuses on nonpharmacological approaches that aim to restore the physiological balance between oxygen delivery to and oxygen demand of the penumbra. Particular emphasis is placed on normobaric oxygen therapy, hypothermia and sensory stimulation. Preclinical evidence and early pilot clinical trials are critically reviewed, and future directions, including clinical translation and trial design issues, are discussed.

Cardiac performance is limited by oxygen delivery to the mitochondria in the crystalloid-perfused working heart.

The left ventricular working, crystalloid-perfused heart is used extensively to evaluate basic cardiac function, pathophysiology, and pharmacology. Crystalloid-perfused hearts may be limited by oxygen delivery, as adding oxygen carriers increases myoglobin oxygenation and improves myocardial function. However, whether decreased myoglobin oxygen saturation impacts oxidative phosphorylation (OxPhos) is unresolved, since myoglobin has a much lower affinity for oxygen than cytochrome c oxidase (COX). In the present study, a laboratory-based synthesis of an affordable perfluorocarbon (PFC) emulsion was developed to increase perfusate oxygen carrying capacity without impeding optical absorbance assessments. In left ventricular working hearts, along with conventional measurements of cardiac function and metabolic rate, myoglobin oxygenation and cytochrome redox state were monitored using a novel transmural illumination approach. Hearts were perfused with Krebs-Henseleit (KH) or KH supplemented with PFC, increasing perfusate oxygen carrying capacity by 3.6-fold. In KH-perfused hearts, myoglobin was deoxygenated, consistent with cytoplasmic hypoxia, and the mitochondrial cytochromes, including COX, exhibited a high reduction state, consistent with OxPhos hypoxia. PFC perfusate increased aortic output from 76 ± 6 to 142 ± 4 ml/min and increased oxygen consumption while also increasing myoglobin oxygenation and oxidizing the mitochondrial cytochromes. These results are consistent with limited delivery of oxygen to OxPhos resulting in an adapted lower cardiac performance with KH. Consistent with this, PFCs increased myocardial oxygenation, and cardiac work was higher over a wider range of perfusate Po2. In summary, heart mitochondria are limited by oxygen delivery with KH; supplementation of KH with PFC reverses mitochondrial hypoxia and improves cardiac performance, creating a more physiological tissue oxygen delivery. NEW & NOTEWORTHY Optical absorbance spectroscopy of intrinsic chromophores reveals that the commonly used crystalloid-perfused working heart is oxygen limited for oxidative phosphorylation and associated cardiac work. Oxygen-carrying perfluorocarbons increase myocardial oxygen delivery and improve cardiac function, providing a more physiological mitochondrial redox state and emphasizing cardiac work is modulated by myocardial oxygen delivery.

Are additive effects of dietary surfactants on intestinal tight junction integrity an overlooked human health risk? - A mixture study on Caco-2 monolayers.

Surfactants may cause dysfunction of intestinal tight junctions (TJs), which is a common feature of intestinal autoimmune diseases. Effects of dietary surfactants on TJ integrity, measured as trans-epithelial resistance (TEER), were studied in Caco-2 cell monolayers. Cytotoxicity was assessed as apical LDH leakage. Monolayers were apically exposed for 60 min to the dietary surfactants solanine and chaconine (SC, potato glycoalkaloids, 0-0.25 mM), perfluorooctane sulfonic acid (PFOS, industrial contaminant, 0-0.8 mM), and sucrose monolaurate (SML, food emulsifier E 473, 0-2.0 mM) separately and as a mixture. Dose-response modelling of TEER EC50 showed that SC were 2.7- and 12-fold more potent than PFOS and SML, respectively. The mixture was composed of 1 molar unit SC, 2.7 units PFOS and 12 units SML ("SC TEER equivalent" proportions 1:1:1). Mixture exposure (0-0.05 mM SC equivalents) dose-response modelling suggested additive action on TJ integrity. Increasing SC and SML concentrations caused increased LDH leakage, but PFOS decreased LDH leakage at intermediate exposure concentrations. In the mixture PFOS appeared to protect from extensive SC- and SML-induced LDH leakage. Complex mixtures of surfactants in food may act additively on intestinal TJ integrity, which should be considered in risk assessment of emulsifier authorisation for use in food production.

Activatable near infrared dye conjugated hyaluronic acid based nanoparticles as a targeted theranostic agent for enhanced fluorescence/CT/photoacoustic imaging guided photothermal therapy.

Targeted theranostic nano-system integrating functions of both diagnosis and therapy shows great potential for improving diagnosis and therapeutic efficacy. Herein, multifunctional nanoparticle based on activatable hyaluronic acid (HA) conjugating two near-infrared (NIR) dyes of Cy5.5 and IR825 was successfully designed and fabricated, and simultaneously used as a carrier for encapsulating perfluorooctylbromide (PFOB). In this system, PFOB showed good capability to absorb the X-rays, Cy5.5 on the outer surface acted as a fluorescent dye activatable by hyaluronidases (Hyals) in the tumor, and IR825 in the core as a photothermal agent. The obtained nanoparticles (NPs) of PFOB@IR825-HA-Cy5.5 can be utilized for triple X-ray computed tomography (CT), fluorescence and photoacoustic imaging. When PFOB@IR825-HA-Cy5.5 NPs were intravenously injected into the mice bearing HT-29 tumor, efficient tumor accumulation was clearly observed, as revealed by the triple modal imaging. An in vivo tumor treatment experiment was conducted by combination of PFOB@IR825-HA-Cy5.5 and near-infrared laser irradiation, achieving effective tumor ablation in mice. Therefore, PFOB@IR825-HA-Cy5.5 NPs is a safe, efficient, imageable photothermal nanoprobe, showing great potential for cancer theranostics.

[Effects of perfluorooctanoic acid on oxidative stress and PPARα and its related CYP4A1 gene expression in rat liver].

OBJECTIVE: To study the effects on oxidative stress and the expression of PPARα-related genes and protein in the liver of rats induced by pentadecafluorooctanoic acid( PFOA). METHODS: A total of 28 male SD rats were randomly divided into four groups: control group: double distilled water, low dose group: PFOA 1 mg/( kg·d), middle dose group: PFOA 5 mg/( kg·d), high dose group: PFOA 25 mg/( kg·d), and were administrated by gavage once a day for 14 days take the organization after anesthesia, according to the follow-up experiments need treatment. The activity of oxidative stressrelated enzymes and the content of malondialdehyde( MDA) in liver tissue were detected. The mRNA levels of peroxisome proliferators-activited receptors α( PPARα) and cytochrome P4504A1( CYP4A1) were detected by real-time PCR. The protein expression of PPARα was detected by Western blot. RESULTS: There was significant difference between high dose group and control group of the body weight( P < 0. 05). The liver weight and relative liver weight of the middle and high dose groups were significantly higher than those of the control group( P < 0. 05). The activity of superoxide dismutase( SOD) and glutathione peroxidase( GSH-Px) in the liver of the low dose group were significantly higher than that of the control group( P < 0. 05). The content of MDA in liver of middle and high dose groups were increased by 2. 5 times and 3. 5 times compared with that of control group( P < 0. 05). The expression of PPARα and its regulated CYP4A1 mRNA were significantly increased in low, middle and high dose groups. The expression of PPARα protein in the low, middle and high dose groups were up-regulated. CONCLUSION: PFOA exposure can lead to oxidative stress in rat liver, resulting in antioxidant enzymes SOD and GSH-Px and MDA changes. At the same time, PFOA exposure induced up regulation of PPARα and CYP4A1 in the liver of rats to enhance theß-oxidation of fatty acids, leading to lipid peroxidation, which has obvious toxic effects on rat liver.

Persistent alterations in immune cell populations and function from a single dose of perfluorononanoic acid (PFNA) in C57Bl/6 mice.

Perfluorononanoic acid (PFNA) is a perfluoroalkyl substance (PFAS) that is structurally related to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Whereas PFOA and PFOS are known immunotoxicants, PFNA is less well characterized. Our previous study showed that PFNA has immunomodulatory effects on leukocyte populations and immune function. The present studies sought to determine whether, and to what degree, the immune system recovered 28 days after PFNA exposure. None of the parameters measured had fully recovered. A few parameters had partially recovered, including decreased spleen size and the decreased ratio of the CD4+/CD8+ double-positive population in thymus. The majority of effects of PFNA remained unchanged 28 days after exposure, including decreased proportion of intact thymocytes (as determined by FSC vs SSC), alterations in the ratios of immune cell populations in spleen and the CD4+, CD8+ and double-negative populations in thymus. Notably, PFNA markedly increased the TNFα response to LPS in vivo, and no recovery was evident 28 days after exposure. The effect of PFNA on CD4+ T cells, CD8+ T cells and CD19+ cells was more pronounced in females. The current study demonstrates that a single high dose exposure to PFNA (e.g. as might occur accidentally in an occupational setting) has long-lasting effects on the immune system.

Hextend-perfluorocarbon cocktail inhibits mean arterial pressure response in a rabbit shock model.

BACKGROUND: Hextend (HEX) is standard of care resuscitation fluid for combat-related traumatic hemorrhage. Because HEX has limited oxygen-carrying capacity, combination therapy with oxygen therapeutics could improve oxygen delivery after hemodynamic shock. We hypothesized that addition of perfluorocarbon (PFC) to HEX would improve hemodynamics and oxygen delivery marker response in a rabbit model of hemorrhagic shock. METHODS: Anesthetized New Zealand rabbits (n = 23) were randomly allocated to resuscitation with fresh whole blood (FWB), HEX, or HEX plus PFC (HEX + PFC) after 60 min of hemorrhagic hypotension. Mean arterial pressure (MAP) was sampled every 2-3 min for 120 min postinfusion; MAP profiles were modeled by a one-compartment pharmacokinetic model to determine peak MAP (Pmax), time to peak MAP (tmax), and postinfusion MAP persistence. Arterial blood was sampled every 15 min to examine pH, blood gases PO2 and pCO2, metabolites lactate and glucose, methemoglobin (metHb), and electrolytes. RESULTS: Compared with FWB and HEX, HEX + PFC administration resulted in delayed peak MAP and less persistent (P < 0.0001) MAP elevation; metHb was significantly elevated (P < 0.0001) compared with FWB and HEX. There were no significant differences in PO2, pCO2, or pH. Glucose, hematocrit, and hemoglobin of both HEX and HEX + PFC were significantly lower relative to FWB. Lactate clearance was modest and transient for all treatments; base deficit was significantly more negative for HEX + PFC. CONCLUSIONS: Addition of PFC to HEX did not improve hemodynamics or acidosis. Further dose- and volume-range studies are required to test efficacy of PFC in combination with HEX for hemorrhagic shock.

Effects of perfluorocarbon dodecafluoropentane (NVX-108) on cerebral microvasculature in the healthy rat.

NVX-108, a dodecafluoropentane-based perfluorocarbon (PFC) emulsion, has therapeutic potential as an oxygen- carrying fluid for emergency medical treatment for traumatic brain injury (TBI) and hemorrhagic shock. Potential cerebral vasoactive properties were assessed by directly measuring pial arteriolar vessel diameters before and after a 30 minute intravenous (IV) infusion of 1.0 ml/kg (high dose [H]) or 0.25 ml/kg (low dose [L]) NVX-108 compared to 2.0 ml/kg Saline (control) in healthy anesthetized rats (N = 6/group). Results showed that post-infusion vessel diameters for small (< 50 µm) and medium (50-100 µm)-sized pial arterioles were significantly (p < 0.05) narrower after only the NVX- 108 H infusion although this vasoconstriction was not statistically significant when analyzed as a percentage change in these vessels. Pial arteriolar vessel diameters were not significantly different for mean value or percentage change after either NVX-108 L or Saline infusions. There were no significant post-infusion changes from baseline in systolic, mean or diastolic blood pressures after any of the treatments although post-infusion blood pressure was statistically higher in the NVX-108 L group compared to NVX-108 H and Saline groups. Arterial blood gases, methemoglob in and lactate were not different from baseline or among groups. No adverse events were observed at either dose of NVX-108. In conclusion, neither 0.25 nor 1.0 ml/kg NVX-108 caused vasoconstriction in cerebral pial arterioles of healthy rats nor resulted in blood pressure changes; the compound should be considered for further investigation for TBI therapy.

Artificial oxygen carriers based on perfluorodecalin-filled poly(n-butyl-cyanoacrylate) nanocapsules.

Poly(n-butyl-cyanoacrylate)-nanocapsules filled by perfluorodecalin (PFD) are proposed as potential oxygen carriers for blood substitute. The capsule dispersion is prepared via interfacial polymerisation from a PFD emulsion in water which in turn is generated by spontaneous phase separation. The resulting dispersion is capable of carrying approximately 10% of its own volume of gaseous oxygen, which is approximately half of the capacity of human blood. The volumes of the organic solvents and water are varied within a wide range, connected to a change of the capsule radius between 200 and 400 nm. The principal suitability of the capsule dispersion for intravenous application is proven in first physiological experiments. A total amount of 10 ml/kg body weight has been infused into rats, with the dispersion supernatant and a normal saline solution as controls. After the infusion of nanocapsules, the blood pressure as well as the heart rate remains constant on a normal level.

Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21.

Despite recent advancement in medicine, nearly 50% of patients with colorectal cancer show recurrence of the disease. Although the reasons for the high relapse are not fully understood, the presence of chemo- and radiotherapy-resistant cancer stem/stem-like cells, where many oncomirs like microRNA-21 (miR-21) are upregulated, could be one of the underlying causes. miR-21 regulates the processes of invasion and metastasis by downregulating multiple tumor/metastatic suppressor genes including PTEN (phosphatase and tensin homolog). Tumor suppressor protein PTEN controls self-renewal of stem cells. Indeed, our current data demonstrate a marked downregulation of PTEN in SCID mice xenografts of miR-21 over-expressing colon cancer HCT116 cells. Colonospheres that are highly enriched in cancer stem/stem like cells reveal increased miR-21 expression and decreased PTEN. Difluorinated curcumin (CDF), a novel analog of the dietary ingredient curcumin, which has been shown to inhibit the growth of 5-Flurouracil + Oxaliplatin resistant colon cancer cells, downregulated miR-21 in chemo-resistant colon cancer HCT116 and HT-29 cells and restored PTEN levels with subsequent reduction in Akt phosphorylation. Similar results were also observed in metastatic colon cancer SW620 cells. Since PTEN-Akt confers drug resistance to different malignancies including colorectal cancer, our observation of normalization of miR-21-PTEN-Akt pathway by CDF suggests that the compound could be a potential therapeutic agent for chemotherapy-resistant colorectal cancer.

Endobronchial perfluorocarbon reduces inflammatory activity before and after lung transplantation in an animal experimental model.

BACKGROUND: The aim of this study was to evaluate the use of liquid perfluorocarbon (PFC) as an adjuvant substance for lung preservation and assess its role in pulmonary protection after transplantation. METHODS: Seventy-two rat lungs were flushed with low-potassium dextran (LPD) solution and randomized into three main groups: control with LPD alone and experimental with 3 (PFC3) and 7 mL/kg (PFC7) of endobronchial PFC instilled just after harvest. Each group was divided into four subgroups according to preservation time (3, 6, 12, and 24 hours). Afterwards, we performed lung transplantation using rat lungs preserved for 12 hours with LPD alone or with 7 mL/kg of endobronchial PFC. RESULTS: There was a significant increase in oxidative stress in the control group at 6 h of cold ischemic time compared with the PFC3 and PFC7 groups. The apoptotic activity and NF-κB expression were significantly higher in the control group compared with the PFC groups at 3, 12, and 24 h of cold preservation. After transplantation, the NF-κB, iNOS, and nitrotyrosine expression as well as caspase 3 activity were significantly lower in the PFC groups. CONCLUSION: The use of endobronchial PFC as an adjuvant to the current preservation strategy improved graft viability.

F4H5: a novel substance for the removal of silicone oil from intraocular lenses.

AIM: Adherent silicone oil on intraocular lenses (IOLs) following retinal detachment surgery induces large and irregular refractive errors and multiple images, and gives rise to glare, distorted and often poor vision. Its removal remains challenging, often requiring mechanical wiping or explantation. F4H5 is a new semifluorinated alkane into which silicone oil is readily soluble. The aim is to establish the effectiveness of F4H5 in removing silicone oil from three different types of IOL in vitro. METHOD: Silicone lenses (Tecnis ZM900, Advanced Medical Optics, Inc.), hydrophobic acrylic lenses (MA60, Alcon Laboratories, Inc.) and PMMA lenses (Ocular Vision, Inc) were first immersed in phosphate-buffered saline, second in silicone oil, then in F4H5 (Fluoron GmbH) for 10 min and lastly vigorously agitated in F4H5 for 1 min. They were weighed at each stage using scales accurate to 0.0001 g to measure the weight of the adherent oil. Dynamic contact angle (DCA) analysis was used to assess their surface properties. RESULTS: Immersion in F4H5 alone removed 96.1% (+/-1.23) by weight of silicone oil from the hydrophobic acrylic lenses, 91.4% (+/-1.58) from the silicone and 95.6% (+/-1.44) from the PMMA IOLs. Immersion combined with 1 min of agitation increased the removal to 98.8% (+/-0.46) from the acrylic IOLs, to 93.7% (+/-0.48) from the silicone IOLs and to 100% (within +/-0.0001 g) from every PMMA IOL. After treatment with F4H5, all IOL were optically clear. DCA hysteresis curves remained permanently altered. All measurements were highly reproducible. CONCLUSION: F4H5 was highly effective at removing the bulk of the silicone oil from all three groups of IOL. The DCA measurements suggested that their surface properties were permanently modified.

The use of a synthetic oxygen carrier-enriched hydrogel to enhance mesenchymal stem cell-based bone formation in vivo.

A major hurdle to surmount in bone-tissue engineering is ensuring a sufficient oxygen supply to newly forming tissue to avoid cell death or delayed development of osteogenic features. We hypothesized that an oxygen-enriched hydrogel scaffold would enhance tissue-engineered bone formation in vivo. To test this, we used a well-characterized mesenchymal stem cell (MSC) line, Tet-off BMP2 MSC, whose cells were engineered to express recombinant human bone morphogenetic protein-2. Cells were suspended in hydrogel supplemented with perfluorotributylamine (PFTBA) and implanted subcutaneously in an ectopic site, a radial bone defect, or a lumbar paravertebral muscle (mouse model of spinal fusion) in C3H/HeN mice. For controls, we used cells suspended in the same gel without PFTBA. In the ectopic site, there were significant increases in bone formation (2.5-fold increase), cell survival, and osteocalcin activity in the PFTBA-supplemented groups. PFTBA supplementation significantly increased structural parameters of bone in radial bone defects and triggered a significant 1.4-fold increase in bone volume in the spinal fusion model. We conclude that synthetic oxygen carrier supplementation of tissue-engineered implants enhances ectopic bone formation and yields better bone quality and volume in bone-repair and spinal fusion models, probably due to increased cell survival.

Perfluorocarbon emulsions as a promising technology: a review of tissue and vascular gas dynamics.

Perfluorocarbon (PFC) emulsions are halogen-substituted carbon nonpolar oils with resultant enhanced dissolved respiratory gas (O(2), N(2), CO(2), nitric oxide) capabilities. In the first demonstration of enhanced O(2) solubility, inhaled PFC could sustain rat metabolism. Intravenous emulsions were then trialed as "blood substitutes." In the last 10 yr, biocomputational modeling has enhanced our mechanistic understanding of PFCs. Contemporary research is now taking advantage of these physiological discoveries and applying PFCs as "oxygen therapeutics," as well as ways to enhance other gas movements. One particularly promising area of research is the treatment of gas embolism (arterial and venous emboli/decompression sickness). An expansive understanding of PFC-enhanced diffusive gas movements through tissue and vasculature may have analogous applications for O(2) or other respiratory gases and should provide a revolution in medicine. This review will stress the fundamental knowledge we now have regarding how respiratory gas movements are changed when intravenous PFC is present.