In vitro microvascular engineering approaches and strategies for interstitial tissue integration.

The increasing gap between clinical demand for tissue or organ transplants and the availability of donated tissue highlights the emerging opportunities for lab-grown or synthetically engineered tissue. While the field of tissue engineering has existed for nearly half a century, its clinical translation remains unrealised, in part, due to a limited ability to engineer sufficient vascular supply into fabricated tissue, which is necessary to enable nutrient and waste exchange, prevent cellular necrosis, and support tissue proliferation. Techniques to develop anatomically relevant, functional vascular networks in vitro have made significant progress in the last decade, however, the challenge now remains as to how best incorporate these throughout dense parenchymal tissue-like structures to address diffusion-limited development and allow for the fabrication of large-scale vascularised tissue. This review explores advances made in the laboratory engineering of vasculature structures and summarises recent attempts to integrate vascular networks together with sophisticated in vitro avascular tissue and organ-like structures. STATEMENT OF SIGNIFICANCE: The ability to grow full scale, functional tissue and organs in vitro is primarily limited by an inability to adequately diffuse oxygen and nutrients throughout developing cellularised structures, which generally results from the absence of perfusable vessel networks. Techniques to engineering both perfusable vascular networks and avascular miniaturised organ-like structures have recently increased in complexity, sophistication, and physiological relevance. However, integrating these two essential elements into a single functioning vascularised tissue structure represents a significant spatial and temporal engineering challenge which is yet to be surmounted. Here, we explore a range of vessel morphogenic phenomena essential for tissue-vascular co-development, as well as evaluate a range of recent noteworthy approaches for generating vascularised tissue products in vitro.

Skeletal Lead Burden of the British Royal Navy in Colonial Antigua.

Lead (Pb) has been known to be a cause of human poisoning since ancient times, but despite this, it was a widely used metal in the European colonial period. In this study, the relationship between Pb exposure and the demographic variables ancestry and age was explored by comparing the bone Pb levels of individuals that were of either African or European ancestry, excavated from a British Royal Navy hospital cemetery (1793-1822 CE) at English Harbour in Antigua, West Indies. More direct comparisons of Pb levels between the two ancestral groups were possible in this study because of the unsegregated nature of this cemetery. Inductively coupled plasma mass spectrometry was used to determine bulk Pb levels in cortical bone samples from the fibular diaphyses of 23 male individuals. No significant difference was found between the distributions of the Pb levels of the ancestral groups (p = 0.94). Further, no positive correlations or significant differences were found in relation to the individuals' ages and their Pb levels (p = 0.24). Levels of Ba, Ca and rare earth elements support a largely biogenic origin of lead. This is bolstered by Pb deposition patterns, generated by synchrotron X-ray fluorescence imaging for another study. The data suggest that naval personnel, regardless of ancestry at English Harbour, had very similar experiences with regard to Pb exposure. Their exposure to the toxic metal was likely not consistent over time as steady exposure would have resulted in accumulation of Pb with age. This study contributes to addressing historical questions regarding the prevalence of Pb poisoning within the British Royal Navy during the colonial period.

Templating the 3D structure of conducting polymers with self-assembling peptides.

Self-assembly of a tetrapeptide covalently attached to a thiophene-based monomer produced a gel with a fibrous, porous structure. Conditions were identified in which the thiophene end groups could undergo polymerization while retaining the 3D structure, resulting in the formation of nanofibrous gels with conductivities averaging 10-4 S cm-1.

Mimicking muscle fiber structure and function through electromechanical actuation of electrospun silk fiber bundles.

Here we detail the fabrication and testing of artificial muscles fabricated from composites of the natural biopolymer silk fibroin and conducting polymers. Aligned nanofiber bundles of silk that mimic the structure of skeletal muscles were produced via electrospinning, and the fibers were infused with conducting polymers using chemical and electrochemical in situ polymerization methods. The resulting bundles of individual, electroactive fibers underwent electromechanical actuation in biologically-relevant electrolyte solutions when low potentials were applied, thus mimicking the contractile function of native muscles. The fabrication methods, bulk mechanical properties, stress and strain generation, and stability under repeated actuation for fiber bundles coated with different conducting polymer formulations are presented.

Comparison of simple measures of insulin sensitivity in young girls with premature adrenarche: the fasting glucose to insulin ratio may be a simple and useful measure.

Insulin resistance is a strong predictor of the development of type 2 diabetes mellitus and cardiovascular disease. Girls with premature adrenarche (PA) or obesity may be at an increased risk for the development of insulin resistance. Recently, in prepubertal girls with PA, a fasting glucose to insulin ratio (FGIR) of less than 7 was found to be predictive of insulin resistance as determined by the frequently sampled iv glucose tolerance test. We sought to compare the FGIR with 2 insulin sensitivity measures, SiM (an adjusted mean measure of insulin sensitivity based on fasting and 2 h post glucose load insulin sensitivity measures) and the composite whole body insulin sensitivity index, ISI(comp), both derived from the 2-h oral glucose tolerance test in 2 groups of children at risk: girls with PA and obese girls. We studied 25 prepubertal girls with PA and/or obesity and further classified them as insulin resistant (IR) or insulin sensitive (IS) based on the FGIR. Four simple measures of insulin sensitivity [FGIR, quantitative insulin sensitivity check index (QUICKI), fasting insulin resistance index, and fasting insulin] were compared with SiM and ISI(comp). Additionally, we characterized the subjects in terms of risk factors associated with insulin resistance according to their insulin resistance status based on the FGIR. In our subjects the strongest correlations overall appeared to be between FGIR and SiM, FGIR and ISI(comp), QUICKI and SiM, and QUICKI and ISI(comp) [correlations (r) ranged from 0.81--0.84]. Furthermore, the IR group had higher body mass index and body mass index z-scores and triglyceride levels than the IS group and were over 3 times more likely to have triglycerides greater than the 95th percentile compared with national norms. We conclude that the FGIR and QUICKI are highly correlated with oral glucose tolerance test measures of insulin sensitivity. An FGIR less than 7 in young girls with PA or obesity may be helpful in the early identification of children at risk for complications of insulin resistance.

Adherence of clinical isolates of Saccharomyces cerevisiae to buccal epithelial cells.

A number of isolates of Saccharomyces cerevisiae have been associated with disease in immunocompromised individuals. Such isolates display a variety of characteristics that enable colonization and persistence in the host. The aim of the work presented here was to establish whether clinical isolates of S. cerevisiae were capable of adhering to epithelial tissue. Adherence to host tissue has been shown to be crucial to the virulence of the pathogenic yeast Candida albicans, and identification of this ability in S. cerevisiae might indicate a role for adherence in tissue colonization by this emerging pathogen. Clinical S. cerevisiae isolates were found to be capable of adhering to exfoliated buccal epithelial cells (BECs) but to a lesser degree than C. albicans. In contrast to the situation evident with C. albicans, the adherence of S. cerevisiae isolates to BECs was not influenced by the carbon source in which the yeast was grown. Treatment of S. cerevisiae with trypsin or proteinase K resulted in a significant reduction in adherence ability while adherence was unaffected by treatment of cells with mannosidase, thus indicating a possible role for proteins rather than mannoproteins in the adherence of S. cerevisiae to BECs.

Fibroblastic tumor of the abducens nerve. Case report.

Tumors of the cranial nerves are uncommon, and are usually schwannomas or neurofibromas. The authors describe a case of a fibroblastic tumor involving the sixth cranial nerve. Based upon electron microscopy and immunohistochemistry, the tumor was not of nerve-sheath origin, but was comprised of fibroblasts. Clinical, radiographic, and pathological material are presented, and the literature is discussed. This represents the third case report of a tumor of the abducens nerve, and the first report of a fibroma of a cranial or peripheral nerve.