One out of ten independent components shows flipped polarity with poorer data quality: EEG database study.

Independent component analysis (ICA) is widely used today for scalp-recorded EEG analysis. One of the limitations of ICA-based analysis is polarity indeterminacy. It is not easy to find detailed documentations that explains engineering solutions of how the polarity indeterminacy is addressed in a given implementation. We investigated how it is implemented in the case of EEGLAB and also the relation between the outcome of the polarity determination and classification of independent components (ICs) in terms of the estimated nature of the sources (brain, muscle, eye, etc.) using an open database of n = 212 EEG dataset of resting state recordings. We found that (1) about 91% of ICs showed positive-dominant IC scalp topographies; (2) positive-dominant ICs were more associated with brain-originated signals; (3) positive-dominant ICs showed more radial (peaked at 10-30 degrees deviations from the radial axis) dipolar projection pattern with less residual variance from fitting the equivalent current dipole. In conclusion, using the EEGLAB's default ICA algorithm, one out of 10 ICs results in flipping its polarity to negative, which is associated with non-radial dipole orientation with higher residual variance. Thus, we determined EEGLAB biases toward positive polarity in decomposing high-quality brain ICs.

Immunohistochemical Investigation of Mechanoreceptors Within the Injured Scapholunate Ligament.

PURPOSE: Scapholunate ligaments (SLLs) play a well-established role in maintaining carpal alignment and kinematics, and are innervated with sensory mechanoreceptors located within the ligaments. They are involved in the afferent arc of dynamic wrist stability. The aim of this study was to describe the changes in these mechanoreceptor populations in injured SLLs. METHODS: Injured SLLs were collected from human wrists at the time of SLL reconstruction or limited wrist fusion, where the ligament remnants would otherwise be discarded. These specimens were formalin-fixed and paraffin-embedded for immunohistochemical analysis to identify mechanoreceptors, which were then classified by type and location within the ligament. RESULTS: A total of 15 ligaments were collected, with the interval from injury ranging from 39 days-20 years. Eleven ligaments were collected less than one year after injury, and four ligaments were collected two years or more after injury. A total of 66 mechanoreceptors were identified, with 50 mechanoreceptors identified in nine of the 11 specimens collected less than one year after injury. In this group, 54% of the mechanoreceptors resided in the volar subunit, 20% in the dorsal subunit, and 26% in the proximal subunit. Two of the four specimens collected two years or later after injury contained mechanoreceptors, all of which were located in the dorsal subunit. Increasing time from injury demonstrated a decline in mechanoreceptor numbers within the volar subunit. CONCLUSIONS: Mechanoreceptors were consistently located in the SLL, particularly in the volar subunit of specimens collected less than one year after injury. CLINICAL RELEVANCE: Ligament reconstruction techniques aim to primarily reconstitute the biomechanical function of the disrupted SLL; however, re-establishing the afferent proprioceptive capacity of the SLL may be a secondary objective. This suggests the need to consider the reconstruction of its volar subunit particularly in those managed within one year of injury.

Alpha oscillatory activity during attentional control in children with Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder (ADHD), and ASD+ADHD.

BACKGROUND: Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) share impairments in top-down and bottom-up modulation of attention. However, it is not yet well understood if co-occurrence of ASD and ADHD reflects a distinct or additive profile of attention deficits. We aimed to characterise alpha oscillatory activity (stimulus-locked alpha desynchronisation and prestimulus alpha) as an index of integration of top-down and bottom-up attentional processes in ASD and ADHD. METHODS: Children with ASD, ADHD, comorbid ASD+ADHD, and typically-developing children completed a fixed-choice reaction-time task ('Fast task') while neurophysiological activity was recorded. Outcome measures were derived from source-decomposed neurophysiological data. Main measures of interest were prestimulus alpha power and alpha desynchronisation (difference between poststimulus and prestimulus alpha). Poststimulus activity linked to attention allocation (P1, P3), attentional control (N2), and cognitive control (theta synchronisation, 100-600 ms) was also examined. ANOVA was used to test differences across diagnostics groups on these measures. Spearman's correlations were used to investigate the relationship between attentional control processes (alpha oscillations), central executive functions (theta synchronisation), early visual processing (P1), and behavioural performance. RESULTS: Children with ADHD (ADHD and ASD+ADHD) showed attenuated alpha desynchronisation, indicating poor integration of top-down and bottom-up attentional processes. Children with ADHD showed reduced N2 and P3 amplitudes, while children with ASD (ASD and ASD+ADHD) showed greater N2 amplitude, indicating atypical attentional control and attention allocation across ASD and ADHD. In the ASD group, prestimulus alpha and theta synchronisation were negatively correlated, and alpha desynchronisation and theta synchronisation were positively correlated, suggesting an atypical association between attentional control processes and executive functions. CONCLUSIONS: ASD and ADHD are associated with disorder-specific impairments, while children with ASD+ADHD overall presented an additive profile with attentional deficits of both disorders. Importantly, these findings may inform the improvement of transdiagnostic procedures and optimisation of personalised intervention approaches.

Modeling brain dynamic state changes with adaptive mixture independent component analysis.

There is a growing interest in neuroscience in assessing the continuous, endogenous, and nonstationary dynamics of brain network activity supporting the fluidity of human cognition and behavior. This non-stationarity may involve ever-changing formation and dissolution of active cortical sources and brain networks. However, unsupervised approaches to identify and model these changes in brain dynamics as continuous transitions between quasi-stable brain states using unlabeled, noninvasive recordings of brain activity have been limited. This study explores the use of adaptive mixture independent component analysis (AMICA) to model multichannel electroencephalographic (EEG) data with a set of ICA models, each of which decomposes an adaptively learned portion of the data into statistically independent sources. We first show that AMICA can segment simulated quasi-stationary EEG data and accurately identify ground-truth sources and source model transitions. Next, we demonstrate that AMICA decomposition, applied to 6-13 channel scalp recordings from the CAP Sleep Database, can characterize sleep stage dynamics, allowing 75% accuracy in identifying transitions between six sleep stages without use of EEG power spectra. Finally, applied to 30-channel data from subjects in a driving simulator, AMICA identifies models that account for EEG during faster and slower response to driving challenges, respectively. We show changes in relative probabilities of these models allow effective prediction of subject response speed and moment-by-moment characterization of state changes within single trials. AMICA thus provides a generic unsupervised approach to identifying and modeling changes in EEG dynamics. Applied to continuous, unlabeled multichannel data, AMICA may likely be used to detect and study any changes in cognitive states.

Macrophage phenotype in response to implanted synthetic scaffolds: an immunohistochemical study in the rat.

Macrophages predominate among the cells that directly interact with biomaterials and are key orchestrators of host-biomaterial interactions. However, the macrophage response to synthetic scaffolds in particular has not been well studied. The aim of this study was therefore to characterise the macrophage response to several synthetic scaffolds in the rat using immunohistological techniques for a panel of markers of macrophage subclass or activation, including ED1 (CD68), ED2 (CD163), CD80, mannose receptor and inducible nitric oxide synthase (iNOS). Materials were implanted subcutaneously and collected after 6-8 weeks during the chronic phase of the host response. Unmodified polycaprolactone scaffolds uniquely demonstrated a total lack of both macrophage adherence to surfaces and a wider foreign body response compared to scaffolds composed of poly(lactic-co-glycolic acid) (PLGA) and polyurethanes (PURs), with those macrophages present having a clear M2 (MR+, CD80-, iNOS-) phenotype. PLGA scaffolds displayed an M1-dominant (CD80+, iNOS+, MR-) response with substantial foreign body giant cell (FBGC) formation, whilst PUR scaffold FBGCs had a more mixed M1 (CD80+, iNOS+) and M2 (MR+) phenotype. The study also identified that the use of the ED1 antibody in the rat as a pan-macrophage marker is problematic as there is a separate and substantial ED2-positive macrophage population that it does not label, both in response to biomaterials and in normal tissues. The biomaterial-dependent nature of activation for both macrophages and FBGCs was confirmed, and nuanced M1/M2 phenotypes were described.

Genetic Overlap Between Midfrontal Theta Signals and Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in a Longitudinal Twin Cohort.

BACKGROUND: Cognitive control has been strongly linked to midfrontal theta (4-8 Hz) brain activity. Such control processes are known to be impaired in individuals with psychiatric conditions and neurodevelopmental diagnoses, including attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Temporal variability in theta, in particular, has been associated with ADHD, with shared genetic variance underlying the relationship. Here, we investigated the phenotypic and genetic relationships between theta phase variability, theta-related signals (the N2, error-related negativity, and error positivity), reaction time, and ADHD and ASD longitudinally in a large twin study of young adults to investigate the stability of the genetic relationships between these measures over time. METHODS: Genetic multivariate liability threshold models were run on a longitudinal sample of 566 participants (283 twin pairs). Characteristics of ADHD and ASD were measured in childhood and young adulthood, while an electroencephalogram was recorded in young adulthood during an arrow flanker task. RESULTS: Cross-trial theta phase variability in adulthood showed large positive phenotypic and genetic relationships with reaction time variability and both childhood and adult ADHD characteristics. Error positivity amplitude was negatively related phenotypically and genetically to ADHD and ASD at both time points. CONCLUSIONS: We showed significant genetic associations between variability in theta signaling and ADHD. A novel finding from the current study is that these relationships were stable across time, indicating a core dysregulation of the temporal coordination of control processes in ADHD that persists in individuals with childhood symptoms. Error processing, indexed by the error positivity, was altered in both ADHD and ASD, with a strong genetic contribution.

High-throughput confocal airy beam oblique light-sheet tomography of brain-wide imaging at single-cell resolution.

Brain research is an area of research characterized by its cutting-edge nature, with brain mapping constituting a crucial aspect of this field. As sequencing tools have played a crucial role in gene sequencing, brain mapping largely depends on automated, high-throughput and high-resolution imaging techniques. Over the years, the demand for high-throughput imaging has scaled exponentially with the rapid development of microscopic brain mapping. In this paper, we introduce the novel concept of confocal Airy beam into oblique light-sheet tomography named CAB-OLST. We demonstrate that this technique enables the high throughput of brain-wide imaging of long-distance axon projection for the entire mouse brain at a resolution of 0.26 µm × 0.26 µm × 1.06 µm in 58 hours. This technique represents an innovative contribution to the field of brain research by setting a new standard for high-throughput imaging techniques.

Midfrontal Theta Activity in Psychiatric Illness: An Index of Cognitive Vulnerabilities Across Disorders.

There is an urgent need to identify the mechanisms that contribute to atypical thinking and behavior associated with psychiatric illness. Behavioral and brain measures of cognitive control are associated with a variety of psychiatric disorders and conditions as well as daily life functioning. Recognition of the importance of cognitive control in human behavior has led to intensive research into behavioral and neurobiological correlates. Oscillations in the theta band (4-8 Hz) over medial frontal recording sites are becoming increasingly established as a direct neural index of certain aspects of cognitive control. In this review, we point toward evidence that theta acts to coordinate multiple neural processes in disparate brain regions during task processing to optimize behavior. Theta-related signals in human electroencephalography include the N2, the error-related negativity, and measures of theta power in the (time-)frequency domain. We investigate how these theta signals are affected in a wide range of psychiatric conditions with known deficiencies in cognitive control: anxiety, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, and substance abuse. Theta-related control signals and their temporal consistency were found to differ in most patient groups compared with healthy control subjects, suggesting fundamental deficits in reactive and proactive control. Notably, however, clinical studies directly investigating the role of theta in the coordination of goal-directed processes across different brain regions are uncommon and are encouraged in future research. A finer-grained analysis of flexible, subsecond-scale functional networks in psychiatric disorders could contribute to a dimensional understanding of psychopathology.

Quality of life, functional impairment and continuous performance task event-related potentials (ERPs) in young adults with ADHD and autism: A twin study.

Background: Young adulthood is a key developmental period for understanding outcomes of childhood onset attention-deficit/hyperactivity disorder (ADHD) and autism. Measurement of functional impairment and quality of life (QoL) can provide important information on the real-life challenges associated with these conditions. Event-related potential (ERP) measures from the continuous performance task (CPT) have long been identified as altered in ADHD and autism but the role of these functions in the aetiological pathway to the disorders and associated impact on quality of life in young adulthood is unknown. Method: We investigated the relationships between ADHD and autism, functional impairment, quality of life, and ERP measures from the cued CPT (CPT-OX) in a young adult twin sample (566 participants aged 22.43 ± 0.96 years old). Results: We observed significant phenotypic correlations between ADHD/autism and lower quality of life with specific genetic overlap between ADHD and physical health, psychological, and environmental aspects. We found significant phenotypic and genetic correlations between ADHD and functional impairment in all domains, as well as between autism and impairment in social functioning and lower impairment in risk-taking. Both ADHD and autism were associated with attenuated amplitude of inhibitory and proactive control ERPs, with large genetic contributions to the overlap. We also found significant phenotypic correlations between these ERP measures and Weiss Functional Impairment Rating Scale (WFIRS) and QoL. Conclusion: This is the first study to investigate the phenotypic and genetic relationships between ADHD and autism, functional impairment, quality of life and ERP measures in young adulthood. Our findings could represent a step towards identifying ERP measures that are related to behaviour in the absence of overt symptoms.

Engineering transplantable human lymphatic and blood capillary networks in a porous scaffold.

Due to a relative paucity of studies on human lymphatic assembly in vitro and subsequent in vivo transplantation, capillary formation and survival of primary human lymphatic (hLEC) and blood endothelial cells (hBEC) ± primary human vascular smooth muscle cells (hvSMC) were evaluated and compared in vitro and in vivo. hLEC ± hvSMC or hBEC ± hvSMC were seeded in a 3D porous scaffold in vitro, and capillary percent vascular volume (PVV) and vascular density (VD)/mm2 assessed. Scaffolds were also transplanted into a sub-cutaneous rat wound with morphology/morphometry assessment. Initially hBEC formed a larger vessel network in vitro than hLEC, with interconnected capillaries evident at 2 days. Interconnected lymphatic capillaries were slower (3 days) to assemble. hLEC capillaries demonstrated a significant overall increase in PVV (p = 0.0083) and VD (p = 0.0039) in vitro when co-cultured with hvSMC. A similar increase did not occur for hBEC + hvSMC in vitro, but hBEC + hvSMC in vivo significantly increased PVV (p = 0.0035) and VD (p = 0.0087). Morphology/morphometry established that hLEC vessels maintained distinct cell markers, and demonstrated significantly increased individual vessel and network size, and longer survival than hBEC capillaries in vivo, and established inosculation with rat lymphatics, with evidence of lymphatic function. The porous polyurethane scaffold provided advantages to capillary network formation due to its large (300-600 µm diameter) interconnected pores, and sufficient stability to ensure successful surgical transplantation in vivo. Given their successful survival and function in vivo within the porous scaffold, in vitro assembled hLEC networks using this method are potentially applicable to clinical scenarios requiring replacement of dysfunctional or absent lymphatic networks.

An "off the shelf" vascular allograft supports angiogenic growth in three-dimensional tissue engineering.

OBJECTIVES: Dense angiogenic sprouting occurs from arteriovenous loops (AVLs) incorporating autologous vein grafts inserted into empty plastic chambers in vivo. The purpose of this study was to determine if angiogenesis from the AVL was limited by substituting an "off the shelf" cold-stored allograft vein instead of an autologous vein. METHODS: Four Sprague Dawley rat groups (two AVL configurations × two chamber types) were established for both 2-week and 6-week harvest. Control AVLs were autologous femoral vein grafts harvested from the left femoral vein that were surgically inserted between the cut femoral artery and vein on the right side. Experimental "allograft" AVLs were rat femoral veins cold-stored (4°C, sterile) for 4 to 7 weeks and then microsurgically interposed between the right femoral artery and vein of an unrelated rat. The two AVL types were inserted in one of two plastic chamber types--smooth or perforated. At harvest, the AVL constructs were checked for patency, weighed, their volume determined, and histology undertaken. Morphometric assessment of percent and absolute volume of major tissue components (including blood vessels) at 6 weeks was completed. RESULTS: There were no significant differences between autograft and allograft groups in construct weight, volume, or morphology at 2 or 6 weeks. No statistical differences occurred in the percent or absolute vascular volume of AVLs incorporating a cold-stored allograft vs autologous vein grafts at 6 weeks regardless of the chamber type. However, perforated chambers caused significant increases in construct weight (P = .015), volume (P = .006), and percent and absolute connective tissue volume at 6 weeks (P = .001) compared to smooth chamber constructs, regardless of the graft type. CONCLUSION: Cold-stored small-caliber allografts interposed in AVLs do not inhibit microcirculatory development and can be used in composite tissue engineering.

Spatial and temporal distribution of E. coli contamination on three inland lake and recreational beach systems in the upper Midwestern United States.

Swimming advisories are commonly posted at public beaches across the United States every year. In Iowa, weekly monitoring of public swimming areas at state and county beaches have resulted in the impairment of numerous lakes for fecal indicator bacteria (FIB) contamination, as detected by E. coli. An extensive study was established to assess the relationships between E. coli contamination of nearshore beach water environments, open lake conditions and beach sands in three recreational beach/lake systems currently impaired for FIB contamination across Iowa. A transect/grab sample based sampling design was implemented across the systems with collections spanning from April through October of 2015 and 2016. Collections of E. coli along water transects identified strong near to far shore gradients of decreasing concentrations in all systems. Results indicate that concentrations of E. coli observed in swimming waters consistently disassociate with concentrations in the broader lake environment. Swimming water E. coli concentrations correlated with elevated beach sand E. coli, samples collected from beach sands uncovered concentrations up to 86,500 times higher than adjacent swimming waters. Results from this study indicate that foreshore beach sands and other beach proximate FIB sources serve as the major contributing source for swimming zone advisories. The current methodology used by state and federal officials includes impairing entire lake waterbodies for FIB contamination of the swimming area. These impairment listings do not accurately reflect the condition(s) of the larger lake environment outside the swimming area and fail to account for beach proximate conditions in the assessment process. Further, this approach provides potentially misleading information to the public and may undermine implementation strategies deployed by resource managers aimed at addressing FIB contamination at recreational swimming areas. Views expressed in this paper are those of the authors and do not necessarily reflect the views or policies of the Iowa Department of Natural Resources.

In vivo tissue engineering of an adipose tissue flap using fat grafts and Adipogel.

For decades, plastic surgeons have spent considerable effort exploring anatomical regions for free flap design. More recently, tissue-engineering approaches have been utilised in an attempt to grow transplantable tissue flaps in vivo. The aim of this study was to engineer a fat flap with a vascular pedicle by combining autologous fat grafts and a novel acellular hydrogel (Adipogel) in an established tissue-engineering model comprising a chamber and blood vessel loop. An arteriovenous loop was created in the rat groin from the femoral vessels and positioned inside a perforated polycarbonate chamber. In Group 1, the chamber contained minced, centrifuged autologous fat; in Group 2, Adipogel was added to the graft; and in Group 3, Adipogel alone was used. Constructs were histologically examined at 6 and 12 weeks. In all groups, new tissue was generated. Adipocytes, although appearing viable in the graft at the time of insertion, were predominantly nonviable at 6 weeks. However, by 12 weeks, new fat had formed in all groups and was significantly greater in the combined fat/Adipogel group. No significant difference was seen in final construct total volume or construct neovascularisation between the groups. This study demonstrated that a pedicled adipose flap can be generated in rats by combining a blood vessel loop, an adipogenic hydrogel, and a lipoaspirate equivalent. Success appears to be based on adipogenesis rather than on adipocyte survival, and consistent with our previous work, this adipogenesis occurred subsequent to graft death and remodelling. The regenerative process was significantly enhanced in the presence of Adipogel.

Brain Computer Interfaces for Improving the Quality of Life of Older Adults and Elderly Patients.

All people experience aging, and the related physical and health changes, including changes in memory and brain function. These changes may become debilitating leading to an increase in dependence as people get older. Many external aids and tools have been developed to allow older adults and elderly patients to continue to live normal and comfortable lives. This mini-review describes some of the recent studies on cognitive decline and motor control impairment with the goal of advancing non-invasive brain computer interface (BCI) technologies to improve health and wellness of older adults and elderly patients. First, we describe the state of the art in cognitive prosthetics for psychiatric diseases. Then, we describe the state of the art of possible assistive BCI applications for controlling an exoskeleton, a wheelchair and smart home for elderly people with motor control impairments. The basic age-related brain and body changes, the effects of age on cognitive and motor abilities, and several BCI paradigms with typical tasks and outcomes are thoroughly described. We also discuss likely future trends and technologies to assist healthy older adults and elderly patients using innovative BCI applications with minimal technical oversight.

Nanophotothermolysis of multiple scattered cancer cells with carbon nanotubes guided by time-resolved infrared thermal imaging.

Nanophotothermolysis with long laser pulses for treatment of scattered cancer cells and their clusters is introduced with the main focus on real-time monitoring of temperature dynamics inside and around individual cancer cells labeled with carbon nanotubes. This technique utilizes advanced time- and spatially-resolved thermal radiometry imaging for the visualization of laser-induced temperature distribution in multiple-point absorbing targets. The capability of this approach was demonstrated for monitoring of thermal effects under long laser exposure (from millisecond to seconds, wavelength 1,064 nm, maximum power 1 W) of cervical cancer HeLa cells labeled with carbon nanotubes in vitro. The applications are discussed with a focus on the nanophotothermolysis of small tumors, tumor margins, or micrometastases under the guidance of near-IR and microwave radiometry.

Charge-based scanning probe readback of nanometer-scale ferroelectric domain patterns at megahertz rates.

We present a method for data storage in continuous ferroelectric (FE) media, applicable to storage systems based on one or more scanning probes. Written FE domains are read back in a destructive fashion by applying a constant voltage of magnitude greater than the coercive voltage, as is done in FE random access memory (FeRAM). The resulting flow of screening charges through the readback amplifier provides sufficient signal to allow readback of domains of minimum dimension of the order of 10 nm at MHz rates, orders of magnitude faster than previously demonstrated techniques for readback of domains in continuous FE media.

Remote Control in Formation of 3D Multicellular Assemblies Using Magnetic Forces.

Cell constructs have been utilized as building blocks in tissue engineering to closely mimic the natural tissue and also overcome some of the limitations caused by two-dimensional cultures or using scaffolds. External forces can be used to enhance the cells' adhesion and interaction and thus provide better control over production of these structures compared to methods like cell seeding and migration. In this paper, we demonstrate an efficient method to generate uniform, three-dimensional cell constructs using magnetic forces. This method produced spheroids with higher densities and more symmetrical structures than the commonly used centrifugation method for production of cell spheroids. It was also shown that shape of the cell constructs could be changed readily by using different patterns of magnetic field. The application of magnetic fields to impart forces on the cells enhanced the fusion of these spheroids, which could be used to produce larger and more complicated structures for future tissue engineering applications.

Bio-engineering a tissue flap utilizing a porous scaffold incorporating a human induced pluripotent stem cell-derived endothelial cell capillary network connected to a vascular pedicle.

Tissue flaps are used to cover large/poorly healing wounds, but involve complex surgery and donor site morbidity. In this study a tissue flap is assembled using the mammalian body as a bioreactor to functionally connect an artery and vein to a human capillary network assembled from induced pluripotent stem cell-derived endothelial cells (hiPSC ECs). In vitro: Porous NovoSorb™ scaffolds (3 mm × 1.35 mm) were seeded with 200,000 hiPSC ECs ±â€¯100,000 human vascular smooth muscle cells (hvSMC), and cultured for 1-3 days, with capillaries formed by 24 h which were CD31+, VE-Cadherin+, EphB4+, VEGFR2+ and Ki67+, whilst hvSMCs (calponin+) attached abluminally. In vivo: In SCID mice, bi-lateral epigastric vascular pedicles were isolated in a silicone chamber for a 3 week 'delay period' for pedicle capillary sprouting, then reopened, and two hiPSC EC ±â€¯hvSMCs seeded scaffolds transplanted over the pedicle. The chamber was either resealed (Group 1), or removed and surrounding tissue secured around the pedicle + scaffolds (Group 2), for 1 or 2 weeks. Human capillaries survived in vivo and were CD31+, VE-Cadherin+ and VEGFR2+. Human vSMCs remained attached, and host mesenchymal cells also attached abluminally. Systemically injected FITC-dextran present in human capillary lumens indicated inosculation to host capillaries. Human iPSC EC capillary morphometric parameters at one week in vivo were equal to or higher than the same parameters measured in human abdominal skin. This 'proof of concept' study has demonstrated that bio-engineering an autologous human tissue flap based on hiPSC EC could minimize the use of donor flaps and has potential applications for complex wound coverage. STATEMENT OF SIGNIFICANCE: Tissue flaps, used for surgical reconstruction of wounds, require complex surgery, often associated with morbidity. Bio-engineering a simpler alternative, we assembled a human induced pluripotent stem cell derived endothelial cell (hiPSC ECs) capillary network in a porous scaffold in vitro, which when transplanted over a mouse vascular pedicle in vivo formed a functional tissue flap with mouse blood flow in the human capillaries. Therefore it is feasible to form an autologous tissue flap derived from a hiPSC EC capillary network assembled in vitro, and functionally connect to a vascular pedicle in vivo that could be utilized in complex wound repair for chronic or acute wounds.

Selenium nanoparticles as anti-infective implant coatings for trauma orthopedics against methicillin-resistant Staphylococcus aureus and epidermidis: in vitro and in vivo assessment.

Background: Bacterial infection is a common and serious complication in orthopedic implants following traumatic injury, which is often associated with extensive soft tissue damage and contaminated wounds. Multidrug-resistant bacteria have been found in these infected wounds, especially in patients who have multi trauma and prolonged stay in intensive care units.Purpose: The objective of this study was to develop a coating on orthopedic implants that is effective against drug-resistant bacteria. Methods and results: We applied nanoparticles (30-70nm) of the trace element selenium (Se) as a coating through surface-induced nucleation-deposition on titanium implants and investigated the antimicrobial activity against drug resistant bacteria including Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-resistant Staphylococcus epidermidis (MRSE) in vitro and in an infected femur model in rats.The nanoparticles were shown in vitro to have antimicrobial activity at concentrations as low as 0.5ppm. The nanoparticle coatings strongly inhibited biofilm formation on the implants and reduced the number of viable bacteria in the surrounding tissue following inoculation of implants with biofilm forming doses of bacteria. Conclusion: This study shows a proof of concept for a selenium nanoparticle coatings as a potential anti-infective barrier for orthopedic medical devices in the setting of contamination with multi-resistant bacteria. It also represents one of the few (if only) in vivo assessment of selenium nanoparticle coatings on reducing antibiotic-resistant orthopedic implant infections.

Fate of Free Fat Grafts with or without Adipogenic Adjuncts to Enhance Graft Outcomes.

BACKGROUND: Free fat grafting is popular, but it is still unclear how it works. Although focusing on graft survival seems an obvious direction for improving clinical results, the authors' research suggests that long-term volume retention is in part attributable to new fat regeneration. Measures to facilitate adipogenesis may therefore be equally important. METHODS: To investigate the relative roles of survival and regeneration of fat grafts, the authors measured the fate of human lipoaspirate implanted into the scalps of immunodeficient mice, with and without stromal vascular fraction and a porcine extracellular matrix (Adipogel). Specifically, the authors were interested in volume retention, and the composition of implanted or regenerated tissue at 6 and 12 weeks. RESULTS: Free fat grafts exhibited poor volume retention and survival. Almost all of the injected human adipocytes died, but new mouse fat formed peripheral to the encapsulated fat graft. Adipogel and stromal vascular fraction improved proliferation of murine fat and human vasculature. Human CD34 stromal cells were present but only in the periphery, and there was no evidence that these cells differentiated into adipocytes. CONCLUSIONS: In the authors' model, most of the implanted tissue died, but unresorbed dead fat accounted substantially for the long-term, reduced volume. A layer of host-derived, regenerated adipose tissue was present at the periphery. This regeneration may be driven by the presence of dying fat, and it was enhanced by addition of the authors' adipogenic adjuncts. Future research should perhaps focus not only on improving graft survival but also on enhancing the adipogenic environment conducive to fat regeneration.