BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

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The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, and provides not only essential physical scaffolding for the cellular constituents but also initiates crucial biochemical and biomechanical cues that are required for tissue

/pdf/the-extracellular-matrix-at-a-glance-3w9rr8bw3e.pdf

The extracellular matrix at a glance

http://chemotaxis.semmelweis.hu/CHTXhpg/Durotaxis/LoCM_BiophysJ_2000.pdf

Cell Movement Is Guided by the Rigidity of the Substrate

We present the science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technology, that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field.

/pdf/science-and-technology-roadmap-for-graphene-related-two-4q9m7czlkc.pdf

Science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems

RGD modified polymers: biomaterials for stimulated cell adhesion and beyond

The mammary gland consists of a polarized epithelium surrounded by a basement membrane matrix that forms a series of branching ducts ending in hollow, sphere-like acini. Essential roles for the epithelial basement membrane during acinar differentiation, in particular laminin and its integrin receptors, have been identified using mammary epithelial cells cultured on a reconstituted basement membrane. Contributions from fibronectin, which is abundant in the mammary gland during development and tumorigenesis, have not been fully examined. Here, we show that fibronectin expression by mammary epithelial cells is dynamically regulated during the morphogenic process. Experiments with synthetic polyacrylamide gel substrates implicate both specific extracellular matrix components, including fibronectin itself, and matrix rigidity in this regulation. Alterations in fibronectin levels perturbed acinar organization. During acinar development, increased fibronectin levels resulted in overproliferation of mammary epithelial cells and increased acinar size. Addition of fibronectin to differentiated acini stimulated proliferation and reversed growth arrest of mammary epithelial cells negatively affecting maintenance of proper acinar morphology. These results show that expression of fibronectin creates a permissive environment for cell growth that antagonizes the differentiation signals from the basement membrane. These effects suggest a link between fibronectin expression and epithelial cell growth during development and oncogenesis in the mammary gland. [Cancer Res 2008;68(9):3185–92]

https://cancerres.aacrjournals.org/content/canres/68/9/3185.full.pdf

Fibronectin Expression Modulates Mammary Epithelial Cell Proliferation during Acinar Differentiation

Stem cell differentiation is regulated by a variety of cues including growth factors and extracellular matrix (ECM), although the role that the ECM has in this process is less understood. Here we provide examples of how the composition, concentration, and elastic modulus of matrix as well as its temporal and spatial location plays a key role in regulating cell fate. Natural variation of matrix elasticity (Figure 1A), ranging from soft brain tissue to calcified bone, plays an important developmental role for tissues: muscle cells want compliant matrix such that they can deform it during contractions whereas bone cells want a less compliant matrix which they can mineralize. Differentiation of naive mesenchymal stem cells (MSCs) in a microenvironment with a controlled elastic modulus (Figure 1B) mirrors tissue-level elasticity: soft matrices that mimic brain are neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous bone prove osteogenic (Figure 1C). Responses are observed at all levels from RNA to protein production to morphology and cell stiffness. Inhibition of elasticity-directed lineage specification in MSCs and ES cells occurs when non-muscle myosin-II is blocked without strongly perturbing many other aspects of cell function and shape. However, such responses act synergistically with chemical factors where only the combination of both results in differentiation marker expression similar to that of differentiated cell lines. Although growth factors likely have increased influence earlier in development compared to matrix as they signal to cells to produce matrix, ECM maintains the ability to stimulate similar cell responses in embryonic stem (ES). Over the initial week of ES cell differentiation, expression of Nanog, a self-renewal gene, drops 10-fold and is followed by a 3-fold up-regulation in ECM, suggesting an inverse relationship between matrix expression and self-renewal. This is supported by co-localization of matrix and germ layer markers (e.g., GATA4, SOX1, etc.) along with decreased levels of matrix and Nanog. When the elasticity of this matrix was increased by the introduction of cross-linking agents, loss of self-renewal and germ layer commitment is accelerated. Taken together, it appears that stem cells can be significantly influenced by both the chemical and physical aspects of their microenvironment, which should be considered for therapeutic uses of stem cells. Extracellular matrix elasticity directs stem cell differentiation

Extracellular matrix elasticity directs stem cell differentiation.

The extracellular matrix (ECM) is an intricate network of proteins that surrounds cells and has a central role in establishing an environment that is conducive to tissue-specific cell functions. In the case of stem cells, this environment is the stem cell niche, where ECM signals participate in cell fate decisions. In this Commentary, we describe how changes in ECM composition and mechanical properties can affect cell shape and stem cell differentiation. Using chondrogenic differentiation as a model, we examine the changes in the ECM that occur before and during mesenchymal stem cell differentiation. In particular, we focus on the main ECM protein fibronectin, its temporal expression pattern during chondrogenic differentiation, its potential effects on functions of differentiating chondrocytes, and how its interactions with other ECM components might affect cartilage development. Finally, we discuss data that support the possibility that the fibronectin matrix has an instructive role in directing cells through the condensation, proliferation and/or differentiation stages of cartilage formation.

Jean E. Schwarzbauer

Papers

Fibronectin Expression Modulates Mammary Epithelial Cell Proliferation during Acinar Differentiation

Extracellular matrix elasticity directs stem cell differentiation.

Fibronectin and stem cell differentiation – lessons from chondrogenesis

Fibronectin: from gene to protein.

Meet the tenascins: multifunctional and mysterious.