Engineering Organoid Vascularization

The development of increasingly biomimetic human tissue analogs has been a long-standing goal in two important biomedical applications: drug discovery and regenerative medicine. In seeking to understand the safety and effectiveness of newly developed pharmacological therapies and replacement tissues for severely injured non-regenerating tissues and organs, there remains a tremendous unmet need in generating tissues with both functional complexity and scale. Over the last decade, the advent of organoids has demonstrated that cells have the ability to reorganize into complex tissue-specific structures given minimal inductive factors. However, a major limitation in achieving truly in vivo-like functionality has been the lack of structured organization and reasonable tissue size. In vivo, developing tissues are interpenetrated by and interact with a complex network of vasculature which allows not only oxygen, nutrient and waste exchange, but also provide for inductive biochemical exchange and a structural template for growth. Conversely, in vitro, this aspect of organoid development has remained largely missing, suggesting that these may be the critical cues required for large-scale and more reproducible tissue organization. Here, we review recent technical progress in generating in vitro vasculature, and seek to provide a framework for understanding how such technologies, together with theoretical and developmentally inspired insights, can be harnessed to enhance next generation organoid development

Drug discovery through stem cell-based organoid models

The development of new drugs is currently a long and costly process in large part due to the failure of promising drug candidates identified in initial in vitro screens to perform as intended in vivo. New approaches to drug screening are being developed which focus on providing more biomimetic platforms. This review surveys this new generation of drug screening technologies, and provides an overview of recent developments in organoid culture systems which could afford previously unmatched fidelity for testing bioactivity and toxicity. The challenges inherent in such approaches will also be discussed, with a view towards bridging the gap between proof-of-concept studies and a wider implementation within the drug development community. (C) 2014 Elsevier B.V. All rights reserved

Acidic dairy products-evalution sensory

This paper presents a model approach of the author for evaluating the quality level of the acid dairy products. In the situation where most dairy products are now seen only through the view of the chemist analyst, the paper presents in figures the comptetent consumer opinin by means of standards of the sensory analysis. Following an evaluation sensory testing, panelists selected products with the best features, highlighting by scores the correspondence between the theoretical and factual issues related especially to the aroma of a dairy product

Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix

By binding growth factors (GFs), the ECM tightly regulates their activity. We recently reported that the heparin-binding domain II of fibronectin acts as a promiscuous high-affinity GF-binding domain. Here we hypothesized that fibrin, the provisional ECM during tissue repair, also could be highly promiscuous in its GF-binding capacity. Using multiple affinity-based assays, we found that fibrin(ogen) and its heparin-binding domain bind several GFs from the PDGF/VEGF and FGF families and some GFs from the TGF-β and neurotrophin families. Overall, we identified 15 unique binding interactions. The GF binding ability of fibrinogen caused prolonged retention of many of the identified GFs within fibrin. Thus, based on the promiscuous and high-affinity interactions in fibrin, GF binding may be one of fibrin's main physiological functions, and these interactions may potentially play an important and ubiquitous role during tissue repair. To prove this role in a gain-of-function model, we incorporated the heparin-binding domain of fibrin into a synthetic fibrin-mimetic matrix. In vivo, the multifunctional synthetic matrix could fully mimic the effect of fibrin in a diabetic mouse model of impaired wound healing, demonstrating the benefits of generating a hybrid biomaterial consisting of a synthetic polymeric scaffold and recombinant bioactive ECM domains. The reproduction of GF-ECM interactions with a fibrin-mimetic matrix could be clinically useful, and has the significant benefit of a more straightforward regulatory path associated with chemical synthesis rather than human sourcing

Fluid-structure interaction in the aortic valve : implications for surgery and prosthesis design

The aortic valve is a complex and dynamic structure, which, with age, degenerative disease, or genetic abnormality, can become pathological and cease to function as in its natural state. A particularly prevailing disease of the aortic valve occurs when the valve becomes abnormally dilated, and regurgitation, or backflow of blood occurs. When this condition becomes severe and is accompanied by debilitating clinical manifestations, the standard procedure has been to replace the entire aortic root and valve with a composite valve graft incorporating either a mechanical or a bioprosthetic valve, during a type of surgery known as the Bentall procedure. However, both of these options have significant drawbacks for the patient, and for cases in which only the aortic root wall is dilated but the leaflets are still intact, novel surgical reconstruction techniques known as "valve-sparing procedures" have been adopted in recent years. The main idea is to excise only the dilated part of the wall, suturing a synthetic graft conduit in its place and thereby leaving the leaflets intact. A number of variants have been proposed, with a vigorous debate in the surgical community as to which is preferable in restoring valve dynamics and hemodynamics, thus leading to a more durable repair and a more favorable outcome for the patient. The objective of this work is to develop numerical simulation techniques to simulate the behavior of the normal aortic valve, and to quantify the effect that these various procedures, as compared to the benchmark native aortic valve. Various types of computational methods have been developed in the past to study the aortic valve, with an increasing level of sophistication as computational resources have evolved. Most of these studies have been structural finite element analyses, where the valve structures have been loaded with uniform distributed pressure loads in order to simulate the effect of blood. Recent efforts have focuse

Arrays of discrete cell culture microenvironments, methods of making such arrays and uses thereof.

The invention pertains to a combinatorial method of identifying the hydrogel formulations controlling phenotype and fate of difficult-to-culture cell types