A novel biodegradable poly(ε-caprolactone urea)urethane incorporating polyhedral oligomeric silsesquioxane nanocomposite and applications for skin tissue engineering

Skin protects our bodies for a lifetime and extensive loss of this barrier renders the individual susceptible to infections and death. Clinically available treatment options, however, are limited in establishing both functional and cosmetic satisfaction. The work described in this thesis is therefore concerned with the development and characterization of a novel biodegradable nanocomposite system displaying suitable properties as skin tissue engineering scaffolds. A novel family of segmented polyurethanes (PU) with increasing hard segment content based on a poly(ε-caprolactone urea)urethane backbone incorporating POSS nanoparticles was synthesized and analysed in terms of material characteristics and biocompatibility. Incorporation of POSS nanoparticles into the PU backbone yielded mostly amorphous materials as corroborated by distinct glass transitions visible on differential scanning calorimetry spectra. With incrementally increasing hard segment content, ultimate tensile strength increased from ~10 to 21 MPa accompanied by increased values for elastic moduli from 0.03 to 0.06 MPa. Number average molecular weights (Mn) decreased with increasing hard segment content due to a corresponding decrease in the proportion of PCL. Sterilization studies raised fundamental concerns regarding the suitability of conventionally available techniques since hydrolytically and temperature labile polymers are susceptible to degradation. The results obtained suggest 70 % ethanol to be a suitable laboratory-based disinfectant which was further demonstrated to have favourable effects on skin cell compatibility. Degradation studies revealed hard segment-dependent modulation of the degradation rate and the materials’ viscoelasticity. In vivo implantation studies of porous scaffolds demonstrated firm integration with the subcutaneous tissue and extensive vascularization. The results obtained in this work highlight (i) the ability to control scaffold degradation rates and mechanical properties and (ii) cellular as well as in vivo biocompatibility, all of which fundamental in the development of a versatile skin tissue engineering scaffold

Intestinal Microbiota Diversity of Pre-Smolt Steelhead (\u3ci\u3eOncorhynchus mykiss\u3c/i\u3e) Across Six Oregon and Washington Hatcheries

The Pacific Northwest is known for its once-abundant wild salmonid populations that have been in decline for more than 50 years due to habitat destruction and commercial overexploitation. To compensate, federal and state agencies annually release hundreds of thousands of hatchery-reared fish into the wild. However, accumulating data indicate that hatchery fish have lower fitness in natural environments, and that hatchery rearing negatively influences return rates of anadromous salmonids. Recently, mounting evidence revealed that the richness and diversity of intestinal microbial species influence host health. We examined the gut microbiota of pre-migratory hatchery-reared steelhead (Oncorhynchus mykiss) to assess microbial community diversity. The Cascade Mountains serve as an allopatric border between two distinct clades of steelhead that show significant differences in genomic and mitochondrial diversity. We identified differences in core microbiota of hatchery-reared fish that correlate with this divergent phylogeographic distribution. Steelhead sampled from hatcheries east of the Cascades had overall greater core gut microbiota diversity. These differences were found despite similarities in diet and rearing conditions. In addition to taxonomic variation across the geographic divide, we identified significant differences in metabolic pathways using PICRUSt gene prediction software. Our analysis revealed significant enrichment of genes associated with lipid metabolism in the gut microbiome of western fish. 8 of 19 individual lipid metabolism pathways were more prominent in western populations. Lipids are a vital nutritional component for teleost species involved in migration and subsequent return for spawning in natal environments. We hypothesize that the observed differences in lipid metabolism across this phylogenetic divide results from an increased ability of eastern Cascade (O. m. gairdneri) fish to utilize lipids taken in via the diet. This increased absorption and utilization would make lipids less available for the intestinal microbiota of the eastern fish, as evidenced by the lower abundance of lipid metabolism genes in the east. Our research utilizes information from the microbiome to understand the phenotypic implications occurring in segregated populations of hatchery-reared steelhead, further confirming elements of coevolution between an organism and its internal environment

Skin regeneration scaffolds: a multimodal bottom-up approach.

Skin wounds are a major social and financial burden. However, current treatments are suboptimal. The gradual comprehension of the finely orchestrated nature of intercellular communication has stimulated scientists to investigate growth factor (GF) or stem cell (SC) incorporation into suitable scaffolds for local delivery into wound beds in an attempt to accelerate healing. This review provides a critical evaluation of the status quo of current research into GF and SC therapy and subsequent future prospects, including benefits and possible long-term dangers associated with their use. Additionally, we stress the importance of a bottom-up approach in scaffold fabrication to enable controlled factor incorporation as well as production of complex scaffold micro- and nanostructures resembling that of natural extracellular matrix

Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications.

Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials' viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications

Nanostructured Materials for Cardiovascular Tissue Engineering

Substantial progress has been made in the field of cardiovascular tissue engineering with an ever increasing number of clinically viable implants being reported. However, poor cellular integration of constructs remains a major problem. Limitations in our knowledge of cell/substrate interactions and their impact upon cell proliferation, survival and phenotype are proving to be a major hindrance. Advances in nanotechnology have allowed researchers to fabricate scaffolds which mimic the natural cell environment to a greater extent; allowing the elucidation of appropriate physical cues which influence cell behaviour. The ability to manipulate cell/substrate interactions at the micro/nano scale may help to create a viable cellular environment which can integrate effectively with the host tissue. This review summarises the influence of nanotopographical features on cell behaviour and provides details of some popular fabricating techniques to manufacture 3D scaffolds for tissue engineering. Recent examples of the translation of this research into fabricating clinically viable implants for the regeneration of cardiovascular tissues are also provided

Nanostructured Materials for Cardiovascular Tissue Engineering

Substantial progress has been made in the field of cardiovascular tissue engineering with an ever increasing number of clinically viable implants being reported. However, poor cellular integration of constructs remains a major problem. Limitations in our knowledge of cell/substrate interactions and their impact upon cell proliferation, survival and phenotype are proving to be a major hindrance. Advances in nanotechnology have allowed researchers to fabricate scaffolds which mimic the natural cell environment to a greater extent; allowing the elucidation of appropriate physical cues which influence cell behaviour. The ability to manipulate cell/substrate interactions at the micro/nano scale may help to create a viable cellular environment which can integrate effectively with the host tissue. This review summarises the influence of nanotopographical features on cell behaviour and provides details of some popular fabricating techniques to manufacture 3D scaffolds for tissue engineering. Recent examples of the translation of this research into fabricating clinically viable implants for the regeneration of cardiovascular tissues are also provided

Erfassung von Wissensorganisationssystemen in BARTOC - Ergebnis eines Projektseminars an der Hochschule Hannover

Das Basel Register of Thesauri, Ontologies & Classifications (BARTOC) hat sich innerhalb weniger Jahre mit mehr als 2.700 Einträgen zu einem umfangreichen Verzeichnis von Wissensorganisationssystemen entwickelt. Im Sommersemester 2017 wurde diese Entwicklung von einem Projektseminar mit Bachelor-Studierenden der Hochschule Hannover begleitet. Eine Revision und Erweiterung der Inhalte von BARTOC führte zu einer besseren Abdeckung ausgewählter Metadatenfelder. Darüber hinaus wurden verschiedene Statistiken, Informationsmaterialien und ein neues Logo erstellt

MALDI-MSI for the analysis of a 3D tissue-engineered psoriatic skin model

MALDI-MS Imaging is a novel label-free technique that can be used to visualize the changes in multiple mass responses following treatment. Following treatment with proinflammatory cytokine interleukin-22 (IL-22), the epidermal differentiation of Labskin, a living skin equivalent (LSE), successfully modeled psoriasis in vitro. Masson’s trichrome staining enabled visualization and quantification of epidermal differentiation between the untreated and IL-22 treated psoriatic LSEs. Matrix-assisted laser desorption ionization mass spectrometry imaging was used to observe the spatial location of the psoriatic therapy drug acetretin following 48 h treatments within both psoriatic and normal LSEs. After 24 h, the drug was primarily located in the epidermal regions of both the psoriatic and nonpsoriatic LSE models whereas after 48 h it was detectible in the dermis

Computational modelling of wound healing insights to develop new treatments

About 1% of the population will suffer a severe wound during their life. Thus, it is really important to develop new techniques in order to properly treat these injuries due to the high socioeconomically impact they suppose. Skin substitutes and pressure based therapies are currently the most promising techniques to heal these injuries. Nevertheless, we are still far from finding a definitive skin substitute for the treatment of all chronic wounds. As a first step in developing new tissue engineering tools and treatment techniques for wound healing, in silico models could help in understanding the mechanisms and factors implicated in wound healing. Here, we review mathematical models of wound healing. These models include different tissue and cell types involved in healing, as well as biochemical and mechanical factors which determine this process. Special attention is paid to the contraction mechanism of cells as an answer to the tissue mechanical state. Other cell processes such as differentiation and proliferation are also included in the models together with extracellular matrix production. The results obtained show the dependency of the success of wound healing on tissue composition and the importance of the different biomechanical and biochemical factors. This could help to individuate the adequate concentration of growth factors to accelerate healing and also the best mechanical properties of the new skin substitute depending on the wound location in the body and its size and shape. Thus, the feedback loop of computational models, experimental works and tissue engineering could help to identify the key features in the design of new treatments to heal severe wounds