A semi-automated quantum-mechanical workflow for the generation of molecular monolayers and aggregates.

Organic electronics (OE) such as organic light-emitting diodes or organic solar cells represent an important and innovative research area to achieve global goals like environmentally friendly energy production. To accelerate OE material discovery, various computational methods are employed. For the initial generation of structures, a molecular cluster approach is employed. Here, we present a semi-automated workflow for the generation of monolayers and aggregates using the GFNn-xTB methods and composite density functional theory (DFT-3c). Furthermore, we present the novel D11A8MERO dye interaction energy benchmark with high-level coupled cluster reference interaction energies for the assessment of efficient quantum chemical and force-field methods. GFN2-xTB performs similar to low-cost DFT, reaching DFT/mGGA accuracy at two orders of magnitude lower computational cost. As an example application, we investigate the influence of the dye aggregate size on the optical and electrical properties and show that at least four molecules in a cluster model are needed for a qualitatively reasonable description.

Efficient calculation of electronic coupling integrals with the dimer projection method via a density matrix tight-binding potential.

Designing organic semiconductors for practical applications in organic solar cells, organic field-effect transistors, and organic light-emitting diodes requires understanding charge transfer mechanisms across different length and time scales. The underlying electron transfer mechanisms can be efficiently explored using semiempirical quantum mechanical (SQM) methods. The dimer projection (DIPRO) method combined with the recently introduced non-self-consistent density matrix tight-binding potential (PTB) [Grimme et al., J. Chem. Phys. 158, 124111 (2023)] is used in this study to evaluate charge transfer integrals important for understanding charge transport mechanisms. PTB, parameterized for the entire Periodic Table up to Z = 86, incorporates approximate non-local exchange, allowing for efficient and accurate calculations for large hetero-organic compounds. Benchmarking against established databases, such as Blumberger's HAB sets, or our newly introduced JAB69 set and comparing with high-level reference data from ωB97X-D4 calculations confirm that DIPRO@PTB consistently performs well among the tested SQM approaches for calculating coupling integrals. DIPRO@PTB yields reasonably accurate results at low computational cost, making it suitable for screening purposes and applications to large systems, such as metal-organic frameworks and cyanine-based molecular aggregates further discussed in this work.

Intracorporeal or extracorporeal anastomosis after minimally invasive right colectomy: a systematic review and meta-analysis.

PURPOSE: As part of the wide adoption of minimally invasive surgery, intracorporeal anastomosis is becoming increasingly common. The benefits of minimally invasive versus open right colectomy are well known although the additional benefits of an intracorporeal anastomosis, performed laparoscopically or robotically, are unclear. The aim of this study was to assess the current literature comparing intracorporeal and extracorporeal anastomosis in the setting of laparoscopic and robotic-assisted right colectomy. METHODS: A systematic review and meta-analysis was conducted according to PRISMA and AMSTAR methods. Studies included were randomized controlled trials and prospective or retrospective cohort studies, between January 1 2010 and July 1 2021, comparing intracorporeal and extracorporeal anastomosis with laparoscopic and robotic approaches. Four groups were identified: laparoscopic extracorporeal anastomosis (L-ECA), laparoscopic intracorporeal anastomosis (L-ICA), robotic extracorporeal anastomosis (R-ECA), and robotic intracorporeal anastomosis (R-ICA). Operative time, rate of conversion to an open procedure, surgical site infection, reoperation within 30 days, postoperative complications within 30 days, and length of hospital stay were assessed. RESULTS: Twenty-one retrospective cohort studies were included in the final analysis. R-ICA and R-ECA had comparable operative times, but a robotic approach required more time than laparoscopic (68 min longer, p < 0.00001). Conversion to open surgery was 55% less likely in the R-ICA group vs. L-ICA, and up to 94% less likely in the R-ICA group in comparison to the R-ECA group. Length of hospital stay was shorter for R-ICA by a half day vs. R-ECA, and up to 1 day less vs. L-ECA. There were no differences in postoperative complications, reoperations, or surgical site infections, regardless of approach. However, the included studies all had high risks of bias due to confounding variables and patient selection. CONCLUSION: Robotic-assisted right colectomy with intracorporeal anastomosis was associated with shorter length of hospitalization and decreased rate of conversion to open surgery, compared to either laparoscopic or extracorporeal robotic approaches. Prospective studies are needed to better understand the true impact of robotic approach and intracorporeal anastomosis in right colectomy.

A Standardized Approach to Cesarean Surgical Technique and Its Effect on Operative Time and Surgical Morbidity.

OBJECTIVE: To evaluate the impact of a standardized surgical technique for primary cesarean deliveries (CDs) on operative time and surgical morbidity. MATERIALS AND METHODS: Two-year retrospective chart review of primary CD performed around the implementation of a standardized CD surgical technique. The primary outcome was total operative time (TOT). Secondary outcomes included incision-to-delivery time (ITDT), surgical site infection, blood loss, and maternal and fetal injuries. RESULTS: When comparing pre- versus postimplementation surgical times, there was no significant difference in TOT (76.5 vs. 75.9 minutes, respectively; p = 0.42) or ITDT (9.8 vs. 8.8 minutes, respectively; p = 0.06) when the entire cohort was analyzed. Subgroup analysis of CD performed early versus late in an academic year among the pre- and postimplementation groups showed no significant difference in TOT (79.3 early vs. 73.8 minutes late; p = 0.10) or ITDT (10.8 early vs. 8.8 minutes late; p = 0.06) within the preimplementation group. In the postimplementation group, however, there was significant decrease in TOT (80.5 early vs. 71.3 minutes late; p = 0.02) and ITDT (10.6 early vs. 6.8 minutes late; p < 0.01). Secondary outcomes were similar for both groups. CONCLUSION: A standardized surgical technique combined with surgical experience can decrease TOT and ITDT in primary CD without increasing maternal morbidity.

Pregnancy after endometrial ablation: a systematic review.

BACKGROUND: Pregnancies have been reported after endometrial ablation but there is little data regarding subsequent pregnancy outcomes. OBJECTIVE: To review systematically the available evidence regarding pregnancy outcomes after endometrial ablation, in order to equip physicians effectively to counsel women considering endometrial ablation. SEARCH STRATEGY: MEDLINE, Embase, Cochrane, and ClinicalTrials.gov were searched through January 2017. SELECTION CRITERIA: Published and unpublished literature in any language describing pregnancy after endometrial ablation or resection was eligible. DATA COLLECTION AND ANALYSIS: Data about preconception characteristics and pregnancy outcomes were extracted and analysed according to study design of source and pregnancy viability. MAIN RESULTS: We identified 274 pregnancies from 99 sources; 78 sources were case reports. Women aged 26-50 years (mean 37.5 ± 5 years) conceived a median of 1.5 years after ablation (range: 3 weeks prior to 13 years after). When reported, 80-90% had not used contraception. In all, 85% of pregnancies from trial/observational studies ended in termination, miscarriage or ectopic pregnancy. Pregnancies that continued (case report and non-case report sources) had high rates of preterm delivery, caesarean delivery, caesarean hysterectomy, and morbidly adherent placenta. Case reports also frequently described preterm premature rupture of membranes, intrauterine growth restriction, intrauterine fetal demise, uterine rupture, and neonatal demise. CONCLUSIONS: An unexpectedly high rate of pregnancy complications is reported in the available literature (which may reflect publication bias) and high-quality evidence is lacking. However, based on the existing evidence, women undergoing endometrial ablation should be informed that subsequent pregnancy may have serious complications and should be counselled to use reliable contraception after the procedure. TWEETABLE ABSTRACT: Systematic review - pregnancies reported after endometrial ablation have an increased risk of adverse outcomes.

Cumulative Effect of an Antimicrobial Stewardship and Rapid Diagnostic Testing Bundle on Early Streamlining of Antimicrobial Therapy in Gram-Negative Bloodstream Infections.

The use of rapid diagnostic tests (RDTs) enhances antimicrobial stewardship program (ASP) interventions in optimization of antimicrobial therapy. This quasi-experimental cohort study evaluated the combined impact of an ASP/RDT bundle on the appropriateness of empirical antimicrobial therapy (EAT) and time to de-escalation of broad-spectrum antimicrobial agents (BSAA) in Gram-negative bloodstream infections (GNBSI). The ASP/RDT bundle consisted of system-wide GNBSI treatment guidelines, prospective stewardship monitoring, and sequential introduction of two RDTs, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and the FilmArray blood culture identification (BCID) panel. The preintervention period was January 2010 through December 2013, and the postintervention period followed from January 2014 through June 2015. The postintervention period was conducted in two phases; phase 1 followed the introduction of MALDI-TOF MS, and phase 2 followed the introduction of the FilmArray BCID panel. The interventions resulted in significantly improved appropriateness of EAT (95% versus 91%; P = 0.02). Significant reductions in median time to de-escalation from combination antimicrobial therapy (2.8 versus 1.5 days), antipseudomonal beta-lactams (4.0 versus 2.5 days), and carbapenems (4.0 versus 2.5 days) were observed in the postintervention compared to the preintervention period (P < 0.001 for all). The reduction in median time to de-escalation from combination therapy (1.0 versus 2.0 days; P = 0.03) and antipseudomonal beta-lactams (2.2 versus 2.7 days; P = 0.04) was further augmented during phase 2 compared to phase 1 of the postintervention period. Implementation of an antimicrobial stewardship program and RDT intervention bundle in a multihospital health care system is associated with improved appropriateness of EAT for GNBSI and decreased utilization of BSAA through early de-escalation.

Effect of dose reduction on image registration and image quality for cone-beam CT in radiotherapy.

INTRODUCTION: The additional radiation exposure applied to patients undergoing cone-beam computed tomography (CBCT) for image registration in radiation therapy is of great concern. Since a decrease in CBCT dose is linked to a degradation of image quality, the consequences of dose reduction on the registration process have to be investigated. MATERIAL AND METHODS: This paper examines image quality and registration of low-contrast structures on an Elekta XVI for the two treatment areas prostate and chest while gradually decreasing the mAs per frame and the number of projections per CBCT to achieve dose reduction. RESULTS: Ideal results for image quality were obtained for 1.6 mAs/frame and 377 projections in prostate scans and 0.63 mAs/frame and 440 projections in chest images. Lower as well as higher total mAs lead to a decrease in image quality. In spite of poor image quality, registration can be successfully performed even for lowest possible settings. CONCLUSION: The results for registration allow an extensive dose reduction in both treatment areas. Very low mAs, however, do not qualify for clinical use because subjective judgment of the registration process is impossible. Compared to default presets the use of settings for acceptable image quality already permit a decrease in exposure of about 40 % (29.0 to 16.7 mGy) in prostate scans and 60 % (18.3 to 7.7 mGy) in chest scans.

Planning Benchmark Study for Stereotactic Body Radiation Therapy of Pancreas Carcinomas with Simultaneously Integrated Boost and Protection: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE/OBJECTIVE: The proximity or overlap of PTV and OAR poses a major challenge in SBRT of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether Simultaneously Integrated Boost (SIB) and Protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality. MATERIALS/METHODS: A multiparametric specification of desired target doses (GTVD50%, GTVD99%, PTVD95%, PTV0.5cc) with two prescription doses of GTVD50%=5×9.2Gy (46Gy) and GTVD50%=8×8.25Gy (66Gy) and OAR limits were distributed with planning CT and contours from 3 PACA patients. In phase 1, plans were ranked using a scoring system for comparison of trade-offs between GTV/PTV and OAR. In phase 2, re-planning was performed for the most challenging case and prescription with dedicated SIB and SIP contours provided for optimization after group discussion. RESULTS: For all 3 cases and both phases combined, 292 plans were generated from 42 institutions in 5 countries using commonly available treatment planning systems. The GTVD50% prescription was performed by only 76% and 74% of planners within 2% for 5 and 8 fractions, respectively. The GTVD99% goal was mostly reached, while the balance between OAR and target dose showed initial SIB/SIP-like optimization strategies in about 50% of plans. For plan ranking, 149 and 217 score penalties were given for 5 and 8 fractions, pointing to improvement possibilities. For phase 2, the GTVD50% prescription was performed by 95% of planners within 2% and GTVD99% as well as OAR doses were better harmonized with notable less score penalties. Fourteen of 19 planners improved their plan rank, 9 of them by at least 2 ranks. CONCLUSION: Dedicated SIB/SIP concepts in combination with multiparametric prescriptions and constraints can lead to overall harmonized and high treatment plan quality for PACA SBRT. Standardized SIB/SIP treatment planning in multicenter clinical trials appears feasible after group consensus and training.

Interactions between various microbes and ginseng botanicals.

Three kinds of interactions occur between ginseng botanicals and microorganisms: a) spoilage of the botanical by various fungi (e.g., Aspergillus, Penicillium, Alternaria, and Eurotium species) and bacteria; b) transformation of ginsenosides into more bioactive forms by bacteria such as Intrasporangium sp. GS603, Microbacterium sp. GS514, Caulobacter leidyia, Bifidobacterium sp. Int57, Bifidobacterium sp. SJ32, Fusobacterium sp. and Bacteroides sp., and moulds (e.g., Aspergillus niger, Fusarium sacchari, Paecilomyces bainier sp. 229, Rhizopus stolonifer, Myrothecium verrucaria and Acremonium strictum); and c) inhibition of certain bacteria (Propionibacterium acnes, Porphyromonas gingivalis, Staphylococcus aureus, Pseudomonas aeruginosa), fungi (Candida albicans, Aspergillus fumigatus, Fusarium oxysporum) and viruses by ginseng constituents.

Microphase separation in copolymers of hydrophilic PEG blocks and hydrophobic tyrosine-derived segments using simultaneous SAXS/WAXS/DSC.

Hydration- and temperature-induced microphase separations were investigated by simultaneous small- and wide-angle X-ray scattering (SAXS and WAXS) and differential scanning calorimetry (DSC) in a family of copolymers in which hydrophilic poly(ethylene glycol) (PEG) blocks are inserted randomly into a hydrophobic polymer made of either desaminotyrosyl-tyrosine ethyl ester (DTE) or iodinated I(2)DTE segments. Iodination of the tyrosine rings in I(2)DTE increased the X-ray contrast between the hydrophobic and hydrophilic segments in addition to facilitating the study of the effect of iodination on microphase separation. The formation of phase-separated, hydrated PEG domains is of considerable significance as it profoundly affects the polymer properties. The copolymers of DTE (or I(2)DTE) and PEG are a useful model system and the findings presented here may be applicable to other PEG-containing random copolymers as well. In copolymers of PEG and DTE and I(2)DTE, the presence of PEG depressed the glass transition temperature (T(g)) of the copolymer relative to the homopolymer, poly(DTE carbonate), and the DTE/ I(2)DTE segments hindered the crystallization of the PEG segments. In the dry state, at large PEG fractions (> 70 vol%), the PEG domains self-assembled into an ordered structure with 14-18 nm distance between the domains. These domains gave rise to a SAXS peak at all temperatures in the iodinated polymers, but only above the T(g) in non-iodinated polymers, due to the unexpected contrast- match between the crystalline PEG domains and the glassy DTE segments. Irrespective of whether PEG was crystalline or not, immersion of these copolymers in water resulted in the formation of hydrated PEG domains that were 10-20 nm apart. Since both water and the polymer chains must be mobile for the phase separation to occur, the PEG domains disappeared when the water froze, and reappeared as the ice began to melt. This transformation was reversible, and showed hysteresis as did the melting of ice and freezing of the water incorporated into the polymer. PEG-water complexes and PEG-water eutectics were observed in WAXS and DSC scans, respectively.

Evaluation of early clinical failure criteria for gram-negative bloodstream infections.

OBJECTIVES: The aim was the development of early clinical failure criteria (ECFC) to predict unfavourable outcomes in patients with Gram-negative bloodstream infections (GN-BSI). METHODS: Adults with community-onset GN-BSI who survived hospitalization for ≥72 hr at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 1, 2010 to June 30, 2015 were identified. Multivariable logistic regression was used to examine the association between clinical variables between 72 and 96 hr after GN-BSI and unfavourable outcomes (28-day mortality or hospital length of stay >14 days from GN-BSI onset). RESULTS: Among 766 patients, 225 (29%) had unfavourable outcomes. After adjustments for Charlson Comorbidity Index and appropriateness of empirical antimicrobial therapy in multivariable model, predictors of unfavourable outcomes included systolic blood pressure <100 mmHg or vasopressor use (adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.2-2.9), heart rate >100 beats/minute (aOR 1.7, 95% CI 1.1-2.5), respiratory rate ≥22 breaths/minute or mechanical ventilation (aOR 2.1, 95% CI 1.4-3.3), altered mental status (aOR 4.5, 95% CI 2.8-7.1), and white blood cell count >12 000/mm3 (aOR 2.7, 95% CI 1.8-4.1) between 72 and 96 hr after index GN-BSI. Area under receiver operating characteristic curve of ECFC model in predicting unfavourable outcomes was 0.77 (0.84 and 0.71 in predicting 28-day mortality and prolonged hospitalization, respectively). CONCLUSIONS: Risk of 28-day mortality or prolonged hospitalization can be estimated between 72 and 96 hr after GN-BSI using ECFC. These criteria may have clinical utility in management of GN-BSI and may improve methodology of future investigations assessing response to antimicrobial therapy based on a standard evidence-based definition of early clinical failure.

NGF and neurotrophin-3 both activate TrkA on sympathetic neurons but differentially regulate survival and neuritogenesis.

In this report we examine the biological and molecular basis of the control of sympathetic neuron differentiation and survival by NGF and neurotrophin-3 (NT-3). NT-3 is as efficient as NGF in mediating neuritogenesis and expression of growth-associated genes in NGF-dependent sympathetic neurons, but it is 20-40-fold less efficient in supporting their survival. Both NT-3 and NGF induce similar sustained, long-term activation of TrkA, while NGF is 10-fold more efficient than NT-3 in mediating acute, short-term TrkA activity. At similar acute levels of TrkA activation, NT-3 still mediates neuronal survival two- to threefold less well than NGF. However, a mutant NT-3 that activates TrkC, but not TrkA, is unable to support sympathetic neuron survival or neuritogenesis, indicating that NT-3-mediated TrkA activation is necessary for both of these responses. On the basis of these data, we suggest that NGF and NT-3 differentially regulate the TrkA receptor both with regard to activation time course and downstream targets, leading to selective regulation of neuritogenesis and survival. Such differential responsiveness to two ligands acting through the same Trk receptor has important implications for neurotrophin function throughout the nervous system.

The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally occurring sympathetic neuron death.

To determine whether the p75 neurotrophin receptor (p75NTR) plays a role in naturally occurring neuronal death, we examined neonatal sympathetic neurons that express both the TrkA tyrosine kinase receptor and p75NTR. When sympathetic neuron survival is maintained with low quantities of NGF or KCl, the neurotrophin brain-derived neurotrophic factor (BDNF), which does not activate Trk receptors on sympathetic neurons, causes neuronal apoptosis and increased phosphorylation of c-jun. Function-blocking antibody studies indicate that this apoptosis is due to BDNF-mediated activation of p75NTR. To determine the physiological relevance of these culture findings, we examined sympathetic neurons in BDNF-/- and p75NTR-/- mice. In BDNF-/- mice, sympathetic neuron number is increased relative to BDNF+/+ littermates, and in p75NTR-/- mice, the normal period of sympathetic neuron death does not occur, with neuronal attrition occurring later in life. This deficit in apoptosis is intrinsic to sympathetic neurons, since cultured p75NTR-/- neurons die more slowly than do their wild-type counterparts. Together, these data indicate that p75NTR can signal to mediate apoptosis, and that this mechanism is essential for naturally occurring sympathetic neuron death.

Allelic diversity and gene genealogy at the self-incompatibility locus in the Solanaceae.

The self-incompatibility (S) locus of flowering plants offers an example of extreme polymorphism maintained by balancing selection. Estimates of recent and long-term effective population size (Ne) were determined for two solanaceous species by examination of S-allele diversity. Estimates of recent Ne in two solanaceous species differed by an order of magnitude, consistent with differences in the species' ecology. In one species, the evidence was consistent with historical population restriction despite a large recent Ne. In the other, no severe bottleneck was indicated over millions of years. Bottlenecks are integral to founder-event speciation, and loci that are subject to balancing selection can be used to evaluate the frequency of this mode of speciation.

Crystallography of the hexagonal ferrites.

The hexagonal ferrites form an unusual group of complex, ferrimagnetic oxides embodying some 60 known crystal structures. These include phases for which the structural unit cell is larger than that in any known inorganic materials. The various hexagonal ferrite modifications fall into two distinct structural series, each formed by the ordered interlayering (stacking) of two discrete building blocks; these blocks stack along the c crystallographic axis in varying ratios and varying permutations to form strictly coherent, reproducible crystal structures. This mixed-layering aspect of the hexagonal ferrites permits direct, visual observation of the sequence of their subunit-cell stacking elements, after etching, by means of electron microscopy. The sequence of stacked blocks in such structures constitutes the only information lacking for a complete, three-dimensional structure determination. Direct access to this information provides an immediate, unique solution of the crystal structure problem in each case and thereby avoids the dilemmas of a classical diffraction approach to such large unit cells. Ferrite structures with hexagonal c dimensions of 1455 and 1577 angstroms have been uniquely solved by direct electron microscopic readout of surface etch features. One must exercise caution, however, in generalizing these findings to other materials. The method is successful in the case of the hexagonal ferrites because these are mixed-layer structures, wherein the building blocks react at different rates to a specific etchant. Mixed-layer systems are not uncommon in crystallography, and it is likely that similar techniques can be developed for other such materials. Regardless of the validity of this prognosis, however, it is quite evident that high-resolution replica electron microscopy is a most promising tool for the direct observation of surface structure on an ultramicro scale. During the studies reported here replica resolution capability was improved to about 10 angstroms; final resolution is limited by the particle size of the platinum shadowing material. Careful control of experimental conditions during replica preparation or an alternate choice of shadowing material, or both, might reasonably improve the resolution by a factor of 2. This resolution is within the range of most unit cell dimensions and approaches interatomic distances in solid-state materials. The potential of such an experimental capability needs no elaboration.

Achieving molecular orientation in thermally extruded 3D printed objects.

Three-dimensional (3D) printing is used to fabricate tissue scaffolds. Polymer chains in these objects are typically unoriented. The mechanical properties of these scaffolds can be significantly enhanced by proper alignment of polymer chains. However, post-processing routes to increase orientation can be limited by the geometry of the printed object. Here, we show that it is possible to orient polymer chains during printing by optimizing printing parameters to take advantage of the flow characteristics of the polymer. This is demonstrated by printing a polymeric scaffold for meniscus regeneration using poly(desaminotyrosyl-tyrosine dodecyl dodecanedioate), poly(DTD DD). Alignment of polymer chains was achieved by translating the printhead at sufficiently high speeds when the polymer was still in a semi-solid state as it cooled from the fluid state at the tip of the nozzle using a critical combination of nozzle diameter, extrusion pressure, and temperature. The degree of orientation as evaluated by x-ray diffraction and thermal shrinkage, was greater than that of drawn fibers. Significant orientation and defect-free printing was achieved even for scaffolds with complex geometries. The ability to orient polymers during 3D printing has the potential to combine the advantages of 3D printing with the superior mechanical performance of more conventional polymer processing methods, such as drawing.

Angiogenic competency of biodegradable hydrogels fabricated from polyethylene glycol-crosslinked tyrosine-derived polycarbonates.

Synthetic biomaterials can be used as instructive biological milieus to guide cellular behaviour and function. To further realize this application, we synthesized a series of structurally similar hydrogels and tested their ability to modulate angiogenesis. Hydrogels were synthesized from poly(DTE-co-x% DT carbonate) crosslinked by y% poly(ethylene glycol) (PEG). Hydrogel desaminotyrosyl tyrosine (DT) contents (x%) ranged from 10-100%, and crosslink densities (y% PEG-crosslinker) ranged from 5-80%. The hydrogels were fashioned into porous scaffolds with highly interconnected macro- and micro-pore (>100 and 10 mm in diameter, respectively) architecture using poly(DTE-co-10%DT carbonate% crosslinked with 8% PEG. Under physiological conditions (in vitro), the hydrogels degraded into three major products: desaminotyrosyl-tyrosine ethyl ester (DTE), desaminotyrosyl tyrosine (DT), and poly(ethylene glycol)-di-DT-hydrazide (PEG-di-DT hydrazide). Increasing either DT content or crosslink density brought quickened degradation. Because DT and DTE, two of the three major degradation products, have not demonstrated any noticeable cytotoxicity or angiogenic effect in previous studies, we measured the cytotoxicity of PEG-di-DT hydrazide, the third major degradation product. We found that PEG-di-DT hydrazide only displayed significant cytotoxicity at the high concentration of 100 mg/mL. Interestingly, PEG-di-DT hydrazide and its further degradation product PEG-dihydrazide stimulated in vitro endothelial cell migration and tubulogenesis, which is comparable to results found with FGF-beta treatment. Subcutaneous implantation of the PEG-crosslinked poly(DTE-co-10%DT carbonate) scaffolds into the backs of rats elicited greater tissue growth over time and superior vascularization than poly(DTE carbonate) implantation. These results show that this new class of biomaterials has a strong potential to modulate angiogenesis.

Carbon nanotube fibers are compatible with Mammalian cells and neurons.

We demonstrate the biocompatibility of carbon nanotube fibers (CNFs) fabricated from single-wall carbon nanotubes. Produced by a particle-coagulation spinning process, CNFs are "hair-like" conductive microwires, which uniquely combine properties of porous nanostructured scaffolds, high-area electrodes, and permeable microfluidic conduits. We report that CNFs are nontoxic and support the attachment, spreading, and growth of mammalian cells and the extension of processes from neurons in vitro. Our findings suggest that CNF may be employed for an electrical interfacing of nerve cells and external devices.

Tyrosine-derived nanospheres for enhanced topical skin penetration.

The objective of this study was to investigate the passive skin penetration of lipophilic model agents encapsulated within tyrosine-derived nanospheres. The nanospheres were formed by the self-assembly of a biodegradable, non-cytotoxic ABA triblock copolymer. The A-blocks were poly(ethylene glycol) and the hydrophobic B-blocks were oligomers of suberic acid and desaminotyrosyl-tyrosine alkyl esters. These nanospheres had an average hydrodynamic diameter of about 50nm and formed strong complexes with fluorescent dyes, 5-dodecanoylaminofluorescein (DAF, LogD=7.54) and Nile Red (NR, LogD=3.10). These dyes have been used here as models for lipophilic drugs. The distribution of topically applied nanosphere-dye formulations was studied in human cadaver skin using cryosectioning and fluorescence microscopy. Permeation analysis (quantified fluorescence) over a 24h period revealed that the nanospheres delivered nine times more NR to the lower dermis than a control formulation using propylene glycol. For DAF, the nanosphere formulation was 2.5 times more effective than the propylene glycol based control formulation. We conclude that tyrosine-derived nanospheres facilitate the transport of lipophilic substances to deeper layers of the skin, and hence may be useful in topical delivery applications.

Electrospun nanofibrous polymeric scaffold with targeted drug release profiles for potential application as wound dressing.

We have successfully fabricated a dual drug release electrospun scaffold containing an anesthetic, lidocaine, and an antibiotic, mupirocin. Two drugs with different lipophilicities were electrospun from a poly-l-lactic acid (PLLA) solution with a dual spinneret electrospinning apparatus into a single scaffold. The release of the drugs from the scaffold showed different profiles for the two drugs. Lidocaine hydrochloride exhibited an initial burst release (80% release within an hour) followed by a plateau after the first few hours. Mupirocin exhibited only a 5% release in the first hour before experiencing a more sustained release to provide antibacterial action for over 72 h. For comparative purposes, both drugs were spun from a single spinneret and evaluated to determine their release profiles. The scaffold maintained its antibiotic activity throughout the processes of electrospinning and gas sterilization and supported cell viability. It has been reported in the literature that interactions between polymer and drug are known to govern the pattern of drug release from electrospun scaffolds. Here, it was found that the presence of the two drugs in the same polymer matrix altered the release kinetics of at least one drug. Based on the release profiles obtained, the dual spinneret technique was the preferred method of scaffold fabrication over the single spinneret technique to obtain a prototype wound healing device.