Liquid Embolic Agents for Endovascular Embolization: A Review.

Endovascular embolization (EE) has been used for the treatment of blood vessel abnormalities, including aneurysms, AVMs, tumors, etc. The aim of this process is to occlude the affected vessel using biocompatible embolic agents. Two types of embolic agents, solid and liquid, are used for endovascular embolization. Liquid embolic agents are usually injectable and delivered into the vascular malformation sites using a catheter guided by X-ray imaging (i.e., angiography). After injection, the liquid embolic agent transforms into a solid implant in situ based on a variety of mechanisms, including polymerization, precipitation, and cross-linking, through ionic or thermal process. Until now, several polymers have been designed successfully for the development of liquid embolic agents. Both natural and synthetic polymers have been used for this purpose. In this review, we discuss embolization procedures with liquid embolic agents in different clinical applications, as well as in pre-clinical research studies.

A First Look at Childhood Abuse in Women with Obstructive Sleep Apnea.

Study objectives. Women who experienced childhood sexual abuse have higher rates of obesity, a risk factor for obstructive sleep apnea (OSA). We assessed if prior childhood sexual abuse was more common in women with OSA vs. control, with possible mediation by obesity. Methods . We studied 21 women with OSA (age mean±s.d. 59±12 years, body mass index (BMI) 33±8 kg/m 2 , respiratory event index [REI] 25±16 events/hour, Epworth Sleepiness Scale [ESS] 8±5) and 21 women without OSA (age 53±9 years, BMI 25±5 kg/m 2 , REI (in 7/21 women) 1±1 events/hour, ESS 5±3). We evaluated four categories of trauma (general trauma, physical, emotional, and sexual abuse) with the early trauma inventory self-report-short form (ETISR-SF). We assessed group differences in trauma scores with independent samples t-tests and multiple regressions. Parametric Sobel tests were used to model BMI as a mediator for individual trauma scores predicting OSA in women. Results. Early childhood sexual abuse reported on the ETISR-SF was 2.4 times more common in women with vs. without OSA ( p =0.02 for group difference). Other trauma scores were not significantly different between women with and without OSA. However, BMI was a significant mediator ( p =0.02) in predicting OSA in women who experienced childhood physical abuse. Conclusions. Childhood sexual abuse was more common in a group of women with OSA than those without OSA. Additionally, BMI was a mediator for OSA of childhood physical but not sexual abuse. There may be physiological impacts of childhood trauma in women that predispose them to OSA.

Baroreflex sensitivity during rest and pressor challenges in obstructive sleep apnea patients with and without CPAP.

INTRODUCTION: Obstructive sleep apnea (OSA) increases sympathetic vasoconstrictor drive and reduces baroreflex sensitivity (BRS), the degree to which blood pressure changes modify cardiac output. Whether nighttime continuous positive airway pressure (CPAP) corrects BRS in the awake state in OSA remains unclear. We assessed spontaneous BRS using non-invasive continuous BP and ECG recordings at rest and during handgrip and Valsalva challenges, maneuvers that increase vasoconstrictor drive with progressively higher BP, in untreated OSA (unOSA), CPAP-treated OSA (cpOSA) and healthy (CON) participants. METHODS: In a cross-sectional study of 104 participants, 34 unOSA (age mean±std, 50.6±14.1years; Respiratory Event Index [REI] 21.0±15.3 events/hour; 22male), 31 cpOSA (49.6±14.5years; REI 23.0±14.2 events/hour; 22male; self-report 4+hours/night,5+days/week,6months), and 39 CON (42.2±15.0years; 17male), we calculated BRS at rest and during handgrip and Valsalva. Additionally, we correlated BP variability (BPV) with BRS during these protocols. RESULTS: BRS in unOSA, cpOSA and CON was, respectively (mean±sdv in ms/mmHg), at rest: 14.8±11.8, 15.8±17.0, 16.1±11.3; during handgrip 13.3±7.6, 12.7±8.4, 16.4±8.7; and during Valsalva 12.7±8.0, 11.5±6.6, 15.1±8.9. BRS was lower in cpOSA than CON for handgrip (p=0.04) and Valsalva (p=0.03). BRS was negatively correlated with BPV in unOSA during Valsalva and handgrip for cpOSA, both R=-0.4 (p=0.02). BRS was negatively correlated with OSA severity (levels: none, mild, moderate, severe) at R=-0.2 (p=0.04,n=104). CONCLUSIONS: As expected, BRS was lower and BPV higher in OSA during the pressor challenges, and disease severity negatively correlated with BRS. In this cross-sectional study, both CPAP-treated (self-reported) and untreated OSA showed reduced BRS, leaving open whether within-person CPAP improves BRS.

In situ crosslinking temperature-responsive hydrogels with improved delivery, swelling, and elasticity for endovascular embolization.

Endovascular embolization of cerebral aneurysms is a common approach for reducing the risk of often-fatal hemorrhage. However, currently available materials used to occlude these aneurysms provide incomplete filling (coils) or require a complicated, time-consuming delivery procedure (solvent-exchange precipitating polymers). The objective of this work was to develop an easily deliverable in situ forming hydrogel that can occlude the entire volume of an aneurysm. The hydrogel is formed by mixing a solution of a temperature-responsive polymer containing pendent thiol groups (poly(NIPAAm-co-cysteamine) or poly(NIPAAm-co-cysteamine-co-JAAm)) with a solution of poly(ethylene glycol) diacrylate (PEGDA). Incorporation of hydrophilic grafts of polyetheramine acrylamide (JAAm) in the temperature-responsive polymer caused weaker physical crosslinking, facilitated faster and more complete chemical crosslinking, and increased gel swelling. One formulation (30 wt % PNCJ20 + PEGDA) could be delivered for over 220 s after mixing, formed a strong and elastic hydrogel (G' > 6000 Pa) within 30 min and once set, maintained its shape and volume in a model aneurysm under flow. This gel represents a promising candidate water-based material utilizing both physical and chemical crosslinking that warrants further investigation as an embolic agent for saccular aneurysms.

A Novel Compound Plumercine from Plumeria alba Exhibits Promising Anti-Leukemic Efficacies against B Cell Acute Lymphoblastic Leukemia.

The current study was focused to evaluate the antioxidant and the anti-cancerous properties of Plumeria alba. Plumeria alba was chosen due to its existing medicinal values. Antioxidant assays like Superoxide radical scavenging assay, Nitrous Oxide radical scavenging assay, were performed, on the methanolic and ethyl acetate extracts of the plant, that depicts the pro-oxidant nature of the extract. Further, they were tested to check cell viability on B cell Acute Lymphoblastic Leukemia (ALL) Cell line (NALM 6), human lung cancer cell line (A549), T cell Acute Lymphoblastic Leukemia cell line (MOLT4), and PBMC isolated from normal donors utilizing MTT assay. Robust anti-proliferative activity was observed in the case of NALM 6 followed by A549, MOLT4, whereas negligible activity was observed in the case of PBMC. Intrigued by this finding, in silico docking was performed using three bioactive compounds namely Plumericine, Isoplumericine, and 13-O-p-Coumaroylplumieride, unique to Plumeria sp. They were docked against five different cyclins and Cdk proteins responsible for ALL. The compounds have shown satisfactory results and their druggability and ADMET properties were checked further. Plumercine turned out to be the most competent compound and hence can be considered as a potential leukemic drug candidate in the future.

Breathing rate variability in obstructive sleep apnea during wakefulness.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is defined by pauses in breathing during sleep, but daytime breathing dysregulation may also be present. Sleep may unmask breathing instability in OSA that is usually masked by behavioral influences during wakefulness. A breath-hold (BH) challenge has been used to demonstrate breathing instability. One measure of breathing stability is breathing rate variability (BRV). We aimed to assess BRV during rest and in response to BH in OSA. METHODS: We studied 62 participants (31 with untreated OSA: respiratory event index [mean ± SD] 20 ± 15 events/h, 12 females, age 51 ± 14 years, body mass index [BMI] 32 ± 8 kg/m2; 31 controls: 17 females, age 47 ± 13 years; BMI 26 ± 4 kg/m2). Breathing movements were collected using a chest belt for 5 minutes of rest and during a BH protocol (60 seconds baseline, 30 seconds BH, 90 seconds recovery, 3 repeats). From the breathing movements, we calculated median breathing rate (BR) and interquartile BRV at rest. We calculated change in BRV during BH recovery from baseline. Group comparisons of OSA vs control were conducted using analysis of covariance with age, sex, and BMI as covariates. RESULTS: We found 10% higher BRV in OSA vs controls (P < .05) during rest. In response to BH, BRV increased 7% in OSA vs 1% in controls (P < .001). Resting BR was not significantly different in OSA and controls, and sex and age did not have any significant interaction effects. BMI was associated with BR at rest (P < .05) and change in BRV with BH (P < .001), but no significant BMI-by-group interaction effect was observed. CONCLUSIONS: The findings suggest breathing instability as reflected by BRV is high in OSA during wakefulness, both at rest and in response to a stimulus. Breathing instability together with high blood pressure variability in OSA may reflect a compromised cardiorespiratory consequence in OSA during wakefulness. CITATION: Pal A, Martinez F, Akey MA, et al. Breathing rate variability in obstructive sleep apnea during wakefulness. J Clin Sleep Med. 2022;18(3):825-833.

Stress in obstructive sleep apnea.

People with obstructive sleep apnea (OSA) often have psychological symptoms including depression and anxiety, which are commonly treated with anti-depression or anti-anxiety interventions. Psychological stress is a related symptom with different intervention targets that may also improve mental state, but this symptom is not well characterized in OSA. We therefore aimed to describe stress in relation to other psychological symptoms. We performed a prospective cross-sectional study of 103 people, 44 untreated OSA (mean ± s.d. age: 51.2 ± 13.9 years, female/male 13/31) and 57 healthy control participants (age: 46.3 ± 13.8 years, female/male 34/23). We measured stress (Perceived Stress Scale; PSS), excessive daytime sleepiness (Epworth Sleepiness Scale; ESS), depressive symptoms (Patient Health Questionnaire; PHQ-9), and anxiety symptoms (General Anxiety Disorder; GAD-7). We compared group means with independent samples t-tests and calculated correlations between variables. Mean symptom levels were higher in OSA than control, including PSS (mean ± s.d.: OSA = 15.3 ± 6.9, control = 11.4 ± 5.5; P = 0.002), GAD-7 (OSA = 4.8 ± 5.0, control = 2.1 ± 3.9; P = 0.02), PHQ-9 (OSA = 6.9 ± 6.1, control = 2.6 ± 3.8; P = 0.003) and ESS (OSA = 8.1 ± 5.3, control = 5.0 ± 3.3; P = 0.03). Similar OSA-vs-control differences appeared in males, but females only showed significant differences in PHQ-9 and ESS, not PSS or GAD-7. PSS correlated strongly with GAD-7 and PHQ-9 across groups (R = 0.62-0.89), and moderately with ESS. Perceived stress is high in OSA, and closely related to anxiety and depressive symptoms. The findings support testing stress reduction in OSA.

Insular functional organization during handgrip in females and males with obstructive sleep apnea.

STUDY OBJECTIVES: Brain regulation of autonomic function in obstructive sleep apnea (OSA) is disrupted in a sex-specific manner, including in the insula, which may contribute to several comorbidities. The insular gyri have anatomically distinct functions with respect to autonomic nervous system regulation; yet, OSA exerts little effect on the organization of insular gyral responses to sympathetic components of an autonomic challenge, the Valsalva. We further assessed neural responses of insular gyri in people with OSA to a static handgrip task, which principally involves parasympathetic withdrawal. METHODS: We measured insular function with blood oxygen level dependent functional MRI. We studied 48 newly-diagnosed OSA (age mean±std:46.5±9 years; AHI±std:32.6±21.1 events/hour; 36 male) and 63 healthy (47.2±8.8 years;40 male) participants. Subjects performed four 16s handgrips (1 min intervals, 80% subjective maximum strength) during scanning. fMRI time trends from five insular gyri-anterior short (ASG); mid short (MSG); posterior short (PSG); anterior long (ALG); and posterior long (PLG)-were assessed for within-group responses and between-group differences with repeated measures ANOVA (p<0.05) in combined and separate female-male models; age and resting heart-rate (HR) influences were also assessed. RESULTS: Females showed greater right anterior dominance at the ASG, but no differences emerged between OSA and controls in relation to functional organization of the insula in response to handgrip. Males showed greater left anterior dominance at the ASG, but there were also no differences between OSA and controls. The males showed a group difference between OSA and controls only in the ALG. OSA males had lower left activation at the ALG compared to control males. Responses were mostly influenced by HR and age; however, age did not impact the response for right anterior dominance in females. CONCLUSIONS: Insular gyri functional responses to handgrip differ in OSA vs controls in a sex-based manner, but only in laterality of one gyrus, suggesting anterior and right-side insular dominance during sympathetic activation but parasympathetic withdrawal is largely intact, despite morphologic injury to the overall structure.

White matter of perinatally HIV infected older youths shows low frequency fluctuations that may reflect glial cycling.

In perinatally HIV-infected (PHIV) children, neurodevelopment occurs in the presence of HIV-infection, and even with combination antiretroviral therapy (cART) the brain can be a reservoir for latent HIV. Consequently, patients often demonstrate long-term cognitive deficits and developmental delay, which may be reflected in altered functional brain activity. Our objective was to examine brain function in PHIV on cART by quantifying the amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo). Further, we studied ALFF and ReHo changes with neuropsychological performance and measures of immune health including CD4 count and viral loads in the HIV-infected youths. We found higher ALFF and ReHo in cerebral white matter in the medial orbital lobe for PHIV (N = 11, age mean ± sd = 22.5 ± 2.9 years) compared to controls (N = 16, age = 22.5 ± 3.0 years), with age and gender as co-variates. Bilateral cerebral white matter showed increased spontaneous regional activity in PHIV compared to healthy controls. No brain regions showed lower ALFF or ReHo in PHIV compared to controls. Higher log10 viral load was associated with higher ALFF and ReHo in PHIV in bilateral cerebral white matter and right cerebral white matter respectively after masking the outcomes intrinsic to the brain regions that showed significantly higher ALFF and ReHo in the PHIV compared to the control. Reductions in social cognition and abstract thinking in PHIV were correlated with higher ALFF at the left cerebral white matter in the left medial orbital gyrus and higher ReHo at the right cerebral white matter in the PHIV patients. Although neuroinflammation and associated neuro repair were not directly measured, the findings support their potential role in PHIV impacting neurodevelopment and cognition.

Beat-to-beat blood pressure variability in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Cardiovascular comorbidities in obstructive sleep apnea (OSA) are difficult to treat, perhaps due to autonomic dysfunction. We assessed beat-to-beat blood pressure (BP) variability (BPV) in OSA while considering other markers derived from electrocardiogram and continuous BP signals. METHODS: We studied 66 participants (33 participants with OSA: respiratory event index [mean ± SEM]: 21.1 ± 2.7 events/h; 12 females, aged 51.5 ± 2.4 years; body mass index: 32.8 ± 1.4 kg/m²; 33 healthy controls: 20 females; aged 45.3 ± 2.4 years; body mass index: 26.3 ± 0.7 kg/m²). We collected 5-minute resting noninvasive beat-to-beat BP and electrocardiogram values. From BP, we derived systolic, diastolic, and mean BP values, and calculated variability as standard deviations (systolic BPV, diastolic BPV, BPV). We also calculated diastole-to-systole time (time to peak). From the electrocardiogram, we derived QRS markers and calculated heart rate and heart rate variability. We performed a multivariate analysis of variance based on sex and group (OSA vs control), with Bonferroni-corrected post hoc comparisons (P ≤ .05) between groups. We calculated correlations of BPV with biological variables. RESULTS: Multivariate analysis of variance showed effects of diastolic BPV and BPV in OSA; post hoc comparisons revealed high diastolic BPV and BPV only in female participants with OSA vs controls. QRS duration was higher in OSA, with post hoc comparisons showing the effect only in males. BPV correlated positively with heart rate variability in controls but not in participants with OSA. BPV correlated positively with time to peak in females with OSA and OSA combined, whereas there was no BPV-time-to-peak correlation in healthy participants. CONCLUSIONS: The findings show sex-specific autonomic dysfunction reflected in beat-to-beat BP in OSA. The higher BPV may reflect poor baroreflex control or vascular damage in OSA, which are potential precursors to cardiovascular complications.

Functional organization of the insula in men and women with obstructive sleep apnea during Valsalva.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) patients show impaired autonomic regulation, perhaps related to functional reorganization of the insula, which in healthy individuals shows sex-specific anterior and right dominance during sympathetic activation. We examined insular organization of responses to a Valsalva maneuver in OSA with functional magnetic resonance imaging (fMRI). METHODS: We studied 43 newly diagnosed OSA (age mean ± SD: 46.8 ± 8.7 years; apnea-hypopnea index (AHI) ± SD: 32.1 ± 20.1 events/hour; 34 males) and 63 healthy (47.2 ± 8.8 years; 40 males) participants. Participants performed four 18-second Valsalva maneuvers (1-minute intervals, pressure ≥ 30 mmHg) during scanning. fMRI time trends from five insular gyri-anterior short (ASG); mid short (MSG); posterior short (PSG); anterior long (ALG); and posterior long (PLG)-were assessed for within-group responses and between-group differences with repeated measures ANOVA (p < 0.05); age and resting heart rate (HR) influences were also assessed. RESULTS: Right and anterior fMRI signal dominance appeared in OSA and controls, with no between-group differences. Separation by sex revealed group differences. Left ASG anterior signal dominance was lower in OSA versus control males. Left ASG and ALG anterior dominance was higher in OSA versus control females. In all right gyri, only OSA females showed greater anterior dominance than controls. Right dominance was apparent in PSG and ALG in all groups; females showed right dominance in MSG and PLG. OSA males did not show PLG right dominance. Responses were influenced substantially by HR but modestly by age. CONCLUSIONS: Anterior and right insular fMRI dominance appears similar in OSA versus control participants during the sympathetic phase of the Valsalva maneuver. OSA and control similarities were present in just males, but not necessarily females, which may reflect sex-specific neural injury.

Poly(N-isopropylacrylamide)-based dual-crosslinking biohybrid injectable hydrogels for vascularization.

Injectable hydrogels provide a powerful and non-invasive approach for numerous applications in cell transplantation, growth factor delivery, tissue regeneration and so forth. The properties of injectable hydrogels should be well-tuned for specific applications, where their overall design should ensure biocompatibility, non-toxicity, robust mechanical properties, and most importantly the ability to promote vascularization and integration with the host tissue/organ. Among these criteria, vascularization remains a key design element in the development of functional therapeutic hydrogels for successful translation into clinical settings. To that end, there is still a critical need for the development of the next generation of injectable hydrogels with precisely tuned biophysical and biochemical properties which could simultaneously promote tissue vascularization. In this work, we developed a temperature responsive, dual-crosslinking, biohybrid hydrogels, modified with a vasculogenic peptide for applications in regenerative medicine, specifically tissue vascularization. The synthesized hydrogels consisted of poly(N-isopropylacrylamide)-based copolymer, functionalized gelation and angiogenic VEGF-mimetic QK peptide with enhanced shear-thinning and injectability properties. QK peptide is a VEGF-mimetic vasculogenic peptide which binds to VEGF receptors and activates intercellular pathway for vascularization. Apart from the presence of QK peptide, the mechanical properties of the hydrogels were precisely tuned by altering the polymer concentration, enabling successful assembly and endothelial cell network formation. Extended in vitro studies demonstrated successful encapsulation and homogeneous distribution of endothelial cells within the three-dimensional (3D) environment of the hydrogel matrix with significantly enhanced vascularization in presence of the QK peptide as early as 3 days of culture. A small, preliminary in vivo study in mice showed a trend of increased blood vessel formation in hydrogels that incorporated the QK peptide. Overall, our study presents the design and characterization of injectable, dual-crosslinking and vasculogenic hydrogels with controlled properties which could be utilized for numerous applications in regenerative medicine, minimally invasive cell and drug delivery as well as fundamental studies on tissue vascularization and angiogenesis. STATEMENT OF SIGNIFICANCE: In this work, we synthesized a new class of temperature responsive, dual-crosslinking, biohybrid injectable hydrogels with enhanced vascularization properties for broad applications in regenerative medicine and minimally invasive cell/drug delivery. The developed hydrogels properly accommodated 3D culture, assembly and network formation of endothelial cells, as evidenced by in vitro and in vivo studies.

Controlled Redox of Lithium-Ion Endohedral Fullerene for Efficient and Stable Metal Electrode-Free Perovskite Solar Cells.

High efficiency perovskite solar cells have underpinned the rapid growth of the field. However, their low device stability limits further advancement. Hygroscopic lithium bis(trifluoromethanesulfonyl)imide (Li+TFSI-) and metal electrode are the main causes of the device instability. In this work, the redox reaction between lithium-ion endohedral fullerenes and 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobi-fluorene (spiro-MeOTAD) was controlled to optimize the amount of oxidized spiro-MeOTAD and antioxidizing neutral endohedral fullerenes. Application of this mixture to metal-free carbon nanotube (CNT)-laminated perovskite solar cells resulted in 17.2% efficiency with a stability time of more than 1100 h under severe conditions (temperature = 60 °C, humidity = 70%). Such high performance is attributed to the uninhibited charge flow, no metal-ion migration, and the enhanced antioxidizing activity of the devices.

Molecular analysis of muscle progenitor cells on extracellular matrix coatings and hydrogels.

Development of an ex vivo culture system to expand satellite cells, the resident muscle stem cell population, will be necessary for the development of their use as therapeutics. The loss of the niche environment is often cited as the reason that culture results in both the loss of myogenic potential and low re-engraftment rates of these cells. Studies have shown that culture of satellite cells on more elastic substrates maintained their quiescence and potential and increased re-engraftment, but there was limited proliferation. We examined whether substrates composed of extracellular matrix proteins, as either coatings or hydrogels, could support expansion of this population whilst maintaining the potency of these cells. The collagen based hydrogels were very pliant and our studies demonstrate that stiffer substrates are necessary for in vitro proliferation and differentiation of satellite cells, and the ECM composition was not significantly important. Our data further indicates that culture on highly elastic substrates allowed satellite cells to down-regulate myogenic specific transcription factors, resulting in an expression profile similar to a Galert state. These satellite cells could be subsequently cultured on Matrigel and induced to differentiate. Proliferation and gene expression data further indicated that C2C12 cells are not a good proxy for studies of satellite cell proliferation and differentiation on alternative substrates. STATEMENT OF SIGNIFICANCE: Although biomaterials and muscle stem cell-based therapeutics for muscle loss due to trauma and disease have been studied intensely for the last decade, significant challenges remain; satellite cells lose their myogenic potential after in vitro culture, and do not re-engraft efficiently when delivered to skeletal muscle. We cultured adult mouse derived satellite cells and C2C12 cells on biomimetic, extracellular matrix based, hydrogels and coated plates and carried out a detailed analysis of proliferation, differentiation, and gene expression. These studies were designed to allow for the examination of the roles of both matrix composition and elasticity. The data demonstrated that satellite cells were most affected by elasticity. Examining the expression of lineage and cell cycle specific genes provided important insight into the behavior of both cell types, and point to fundamental differences that affect the interpretation of studies aimed at understanding the in vitro requirements of muscle progenitor cells. Understanding how satellite cells respond to various biochemical and biophysical cues at the molecular level will inform future efforts to design therapeutics for muscle regeneration.

Plasma-based fast-gelling biohybrid gels for biomedical applications.

Blood based biomaterials are widely researched and used in different biomedical applications including cell therapy, drug delivery, sealants etc. due to their biocompatibility and biodegradability. Blood derived gels are successfully used in clinical studies due to the presence of fibrinogen and several platelet growth factors. In spite of their wide applications, it is challenging to use blood-based biomaterials due to their low mechanical stability, poor adhesive property and contamination risk. In this study, we used porcine plasma to form gel in presence of biodegradable synthetic crosslinkers. Mechanical strength of this plasma gel could be tailored by altering the amount of crosslinkers for any desired biomedical applications. These plasma gels, formed by the synthetic crosslinkers, were utilized as a drug delivery platform for wound healing due to their low cytotoxicity. A model drug release study with these plasma gels indicated slow and sustained release of the drugs.

Effect of organic cation states on electronic properties of mixed organic-inorganic halide perovskite clusters.

We study the effect of organic cation-centered states in mixed organic-inorganic halide perovskites on the bandstructure and optical properties. Clusters of methylammonium lead iodide (MAPbI3) and bromide (MAPbBr3) and of MAPbI3 (MAPbBr3) in which an organic cation was substituted with formamidinium (FA) and guanidinium (GA) are studied with density functional theory and time-dependent density functional theory. This model permitted comparing bandstructure and optical properties with different organic cations computed with GGA and hybrid functionals. We find that while with MA and GA, cation-centered states are deep in the conduction band, with FA, organic cation-centered states are introduced within as little as 0.5 eV of the conduction band maximum, which are expected to influence electronic and optical properties of perovskites in solar cells and other optoelectronic devices. There is qualitative agreement between a GGA and a hybrid functional; however, the use of a hybrid functional leads to a slightly higher offset of the cation-centered states from the conduction band edge, a different order of electronic states, and much better localization of cation-centered states. Analysis of optical absorption spectra suggests that occupation by photoexcitation of FA-centered states and formation of transient formamidinium species is possible in both I and Br-based perovskites.

Achieving High Efficiency in Solution-Processed Perovskite Solar Cells Using C60/C70 Mixed Fullerenes.

Fullerenes have attracted considerable interest as an electron-transporting layer in perovskite solar cells. Fullerene-based perovskite solar cells produce no hysteresis and do not require high-temperature annealing. However, high power conversion efficiency has been only achieved when the fullerene layer is thermally evaporated, which is an expensive process. In this work, the limitations of a solution-processed fullerene layer have been identified as high crystallinity and the presence of remnant solvents, in contrast to a thermally deposited C60 film, which has low crystallinity and no remaining solvents. As a solution to these problems, a mixed C60 and C70 solution-processed film, which exhibits low crystallinity, is proposed as an electron-transporting layer. The mixed-fullerene-based devices produce power conversion efficiencies as high as that of the thermally evaporated C60-based device (16.7%) owing to improved fill factor and open-circuit voltage. In addition, by vacuum-drying the mixed fullerene film, the power conversion efficiency of the solution-processed perovskite solar cells is further improved to 18.0%. This improvement originates from the enhanced transmittance and charge transport by removing the solvent effect. This simple and low-cost method can be easily used in any type of solar cells with fullerene as the electron-transporting layer.

Comparison of optical absorption spectra of organic molecules and aggregates computed from real frequency dependent polarizability to TD-DFT and the dipole approximation.

We compare the performance of an approach using real frequency dependent polarizability to compute optical absorption spectra to linear-response time-dependent density functional theory (TD-DFT) for small organic dyes, oligomers of different lengths (oligothiophenes), and molecular clusters representing a molecular crystal (pentacene). For pentacene, the spectra computed with the two methods are also compared to the spectrum computed for clusters and the periodic solid using the dipole approximation. The approach based on real polarizability produces spectra in good agreement with TD-DFT for small molecules. The (artificial) redshift for longer oligomers is slightly more significant with the polarizability-based method than with TD-DFT. For pentacene clusters, TD-DFT produces reasonable spectra with a hybrid functional, but a significant redshift is introduced with a generalized gradient approximation functional due to the presence of charge transfer transitions. This problem is slightly attenuated with the polarizability-based method. The dipole approximation results in spectra much redshifted vs both TD-DFT and the polarizability-based method and in a different trend with cluster size.

Therapeutic neovascularization promoted by injectable hydrogels.

The aim of therapeutic neovascularization is to repair ischemic tissues via formation of new blood vessels by delivery of angiogenic growth factors, stem cells or expansion of pre-existing cells. For efficient neovascularization, controlled release of growth factors is particularly necessary since bolus injection of molecules generally lead to a poor outcome due to inadequate retention within the injured site. In this regard, injectable hydrogels, made of natural, synthetic or hybrid biomaterials, have become a promising solution for efficient delivery of angiogenic factors or stem and progenitor cells for in situ tissue repair, regeneration and neovascularization. This review article will broadly discuss the state-of-the-art in the development of injectable hydrogels from natural and synthetic precursors, and their applications in ischemic tissue repair and wound healing. We will cover a wide range of in vitro and in vivo studies in testing the functionalities of the engineered injectable hydrogels in promoting tissue repair and neovascularization. We will also discuss some of the injectable hydrogels that exhibit self-healing properties by promoting neovascularization without the presence of angiogenic factors.

Influence of the aggregate state on band structure and optical properties of C60 computed with different methods.

C60 and C60 based molecules are efficient acceptors and electron transport layers for planar perovskite solar cells. While properties of these molecules are well studied by ab initio methods, those of solid C60, specifically its optical absorption properties, are not. We present a combined density functional theory-Density Functional Tight Binding (DFTB) study of the effect of solid state packing on the band structure and optical absorption of C60. The valence and conduction band edge energies of solid C60 differ on the order of 0.1 eV from single molecule frontier orbital energies. We show that calculations of optical properties using linear response time dependent-DFT(B) or the imaginary part of the dielectric constant (dipole approximation) can result in unrealistically large redshifts in the presence of intermolecular interactions compared to available experimental data. We show that optical spectra computed from the frequency-dependent real polarizability can better reproduce the effect of C60 aggregation on optical absorption, specifically with a generalized gradient approximation functional, and may be more suited to study effects of molecular aggregation.