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At least 127 records · Page 7Linked to original sources

PubMed2005

Microstorms in cellular polymers: a route to soft piezoelectric transducer materials with engineered macroscopic dipoles.

Cellular polymers can be internally charged by "microstorms" (silent or partial discharges) within the voids of the polymer foam. The resulting material, which carries positive and negative charges on the internal void surfaces, is called a ferroelectret. Ferroelectrets behave like typical ferroelectrics, hence they provide a novel class of ferroic materials. The soft foams are strongly piezoelectric and can be used, in a wide range of applications, as transducers for interconverting mechanical and electrical signals. Herein, an overview is provided on the preparation of cellular polymers by physical foaming (extrusion, biaxial stretching, and controlled inflation by pressure treatments), on their charging by "microstorms", on their piezo- and pyroelectricity, and on analogies to ferroelectrics. Finally, a survey of selected applications is presented.

Journal Article↗

PubMedDate not supplied

Strategies for cell engineering in tissue repair.

Cellular and tissue engineering are new areas of research, currently attracting considerable interest because of the remarkable potential they have for clinical application. Some claims have indeed been dramatic, including the possibility of growing complete, artificial organs, such as the liver. However, amid such long-term aspirations there is the very real possibility that small tissues (artificial grafts) may be fabricated in the near future for use in reconstructive surgery. Logically, we should focus on how it is possible to produce modest, engineered tissues for tissue repair. It is evident that strategies to date either depend on innate information within implanted cells, to reform the target tissue or aim to provide appropriate environmental cues or guidance to direct cell behavior. It is argued here that present knowledge of tissue repair biology points us toward the latter approach, providing external cues which will direct how cells should organize the new tissue. This will be particularly true where we need to reproduce microscopic and ultrastructural features of the original tissue architecture. A number of such cues have been identified, and methods are already available, including substrate chemistry, substrate contact guidance, mechanical loading, and biochemical mediators to provide these cues. Examples of these are already being used with some success to control the formation of tissue structures.

Journal Article↗

PubMed2006

Cellular therapy and myocardial tissue engineering: the role of adult stem and progenitor cells.

Acquired cardiovascular diseases and complex congenital heart diseases are leading causes of morbidity and mortality. Cellular therapy and tissue engineering are emerging as promising alternative approaches to treat cardiovascular diseases. Cellular therapy involves isolating cells and delivering the cells to the site of cardiac injury to restore blood flow and contractility to previously infarcted, scarred or dysfunctional heart. Myocardial tissue engineering, engineered heart tissue by seeding cells in three-dimensional matrices of biodegradable polymers or cell sheet engineering without artificial scaffolds to form new myocardial constructs. Questions are common to both these approaches, such as the best cell source and optimal conditions for therapeutic application. The capabilities of stem cells for pluripotency and long-term self-renewal make it an ideal source for myocardial tissue engineering and cell therapy. We review the current understanding of postnatal adult stem and progenitor cells in cellular therapy and myocardial tissue engineering from a surgical view point, and highlight the latest advances in these exciting fields.

Adult↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

PubMed2004

Inverse metabolic engineering with phosphagen kinase systems improves the cellular energy state.

Inverse metabolic engineering attempts to identify or construct desired phenotypes of applied interest to endow them on appropriate host organisms. A particular desirable phenotype is the ATP homeostasis exhibited by animal cells with high and variable ATP turnover through temporal and spatial energy buffering. This buffering is achieved by phosphagen kinase systems that consist of a specific kinase and its cognate phosphagen, which functions as a large pool of 'high-energy phosphates' that are used to replenish ATP during periods of high energetic demand. This review discusses recent advances and potentials of inverse metabolic engineering of cell types that do not normally contain such systems--bacteria, yeast, plants, and liver--with creatine or arginine kinase systems. Examples are discussed that illustrate how microbial metabolism can be tailored for large-scale industrial processes with imperfect mixing and how the liver can be protected from metabolic insults or stimulated for better regeneration.

Adenosine Triphosphate↗

PubMed2005

Antibody engineering, virus retargeting and cellular immunotherapy: one ring to rule them all?

Solid tumours present numerous obstacles for efficient systemic delivery of therapeutic agents. This goal has to face specific problems related to the nature of each targeting element, but also the physical barriers posed by tumours, such as heterogeneous blood supply and elevated interstitial pressure. These barriers impair the delivery to tumours of antibodies or viral particles. Immune cells are supposed to be endowed with the ability to target tumours, but in general, tumour cells themselves provide poor targets for immunological responses. A key challenge of tumour gene therapy (cell carrier- and/or viral vector-mediated) is to control the site at which genes are expressed by instructing cells or virus or to distinguish between target and non-target tissue. Thus, antibody-directed targeting of virus or cells could potentially improve both the safety and the efficacy of therapeutic gene delivery to tumours. Furthermore, virus production can rely on carrier cells under the transcriptional control of a factor activated after specific triggering of a tumour-specific receptor. Given that any of these anti-tumour strategies by themselves have fulfilled their therapeutic potential, we propose here their combination for developing more effective anti-cancer therapies.

Animals↗

PubMed1992

Opportunities for the cellular approach in biomedical engineering.

This review is a commentary on recent, altered perspectives about biomedical engineering and its role in medicine. It is argued that, rather than being a peripheral specialty, medical engineering and engineering principles in general have a direct application to biochemical medicine and cell biology. A brief description is given of the cell as a compartmentalised reactor system, and the ways in which it is possible to replace lost or aberrant cell function. Specific topics are then covered to illustrate the general thesis. These are: polymers for cell mimicry, cell-surface interactions, biomolecule transport, cell transport phenomena, cell signalling, harnessing of cells for therapy and microbial interactions. These disparate subject areas have a common thread of interest for the biomedical engineer, and are presented here in a way which highlights key points of relevance for engineering. Though necessarily brief, the various descriptions in this review provide a film indication that a rigorous approach to the assessment, modelling and use of cells along sound engineering lines is vital for the future. It is concluded that, without this approach, our understanding of cell biology will remain semiquantitative and semiempirical.

Biological Transport↗

PubMed2005

Regulation of cellular infiltration into tissue engineering scaffolds composed of submicron diameter fibrils produced by electrospinning.

We characterize the infiltration of interstitial cells into tissue engineering scaffolds prepared with electrospun collagen, electrospun gelatin, electrospun poly(glycolic) acid (PGA), electrospun poly(lactic) acid (PLA), and an electrospun PGA/PLA co-polymer. Electrospinning conditions were optimized to produce non-woven tissue engineering scaffolds composed of individual fibrils less than 1000 nm in diameter. Each of these materials was then electrospun into a cylindrical construct with a 2 mm inside diameter with a wall thickness of 200-250 microm. Electrospun scaffolds of collagen were rapidly, and densely, infiltrated by interstitial and endothelial cells when implanted into the interstitial space of the rat vastus lateralis muscle. Functional blood vessels were evident within 7 days. In contrast, implants composed of electrospun gelatin or the bio-resorbable synthetic polymers were not infiltrated to any great extent and induced fibrosis. Our data suggests that topographical features, unique to the electrospun collagen fibril, promote cell migration and capillary formation.

Animals↗

PubMed2007

Fluorescent proteins and engineered cell lines.

Green fluorescent protein and other fluorescent proteins provide powerful tools for high content analysis of cellular processes. Engineering fluorescent protein sensors for expression in cellular assays requires consideration of a wide range of design factors to produce fusion proteins capable of generating informative and biologically relevant data while meeting the rigorous demands of high content screening. The target protein, fluorescent protein, host cell line, construct components and orientation, expression level, and other factors all contribute to the performance of the sensor. This chapter reviews the process of selecting an optimum combination of these design elements for engineering cells for high content analysis.

Animals↗

PubMed2005

The Minnesota Molecular and Cellular Therapeutics Facility: a state-of-the-art biotherapeutics engineering laboratory.

Molecular-, gene-, cellular-, and tissue-based therapies have become increasingly acceptable modes of clinical therapy. Regulatory requirements and oversight have increased, and the need for facilities suited for production of such therapies has become more apparent. The Minnesota Molecular and Cellular Therapeutics Facility is a state-of-the-art laboratory at the University of Minnesota, Saint Paul, Minn, that was designed to support production of biologic products for use in clinical trials. A talented staff experienced in the medical, scientific, technical, and regulatory aspects of the development, production, and administration of such products complements the special design and construction of the facility. Hematopoietic stem cells (HSCs) are manipulated for transplant, and current clinical trials involving novel therapies include the use of allogeneic natural killer (NK) cells and tumor vaccines for the treatment of various malignancies and suicide gene-transduced T cells for the prevention of graft-vs-host disease (GVHD) after bone marrow transplantation. Other therapies, including marrow-derived multipotent adult progenitor cells (MAPCs), umbilical cord blood (UCB) stem cells, regulatory T cells, skeletal myoblasts, and monoclonal antibodies, will be used to treat a spectrum of disease and are in various phases of development. Here we provide an overview of the Minnesota Molecular and Cellular Therapeutics (MMCT) Facility, detailing our approach to the manufacture of novel therapeutics and highlighting current and future activities.

Academic Medical Centers↗

PubMed2003

Reprogramming control of an allosteric signaling switch through modular recombination.

Many eukaryotic signaling proteins are composed of simple modular binding domains, yet they can display sophisticated behaviors such as allosteric gating and multi-input signal integration, properties essential for complex cellular circuits. To understand how such behavior can emerge from combinations of simple domains, we engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the "output" domain of N-WASP was recombined with heterologous autoinhibitory "input" domains. Synthetic switch proteins were created with diverse gating behaviors in response to nonphysiological inputs. Thus, this type of modular framework can facilitate the evolution or engineering of cellular signaling circuits.

Actins↗

PubMed2003

Efficient and stable retroviral transfection of ovine endothelial cells with green fluorescent protein for cardiovascular tissue engineering.

To determine whether cellular components of tissue-engineered cardiovascular structures are derived from cells harvested and seeded onto an acellular scaffold, or from cells originating from surrounding tissue (e.g., proximal and distal anastomosis), cellular retroviral transfection with green fluorescent protein (GFP) was used. Ovine endothelial cells (ECs) were transfected with a Moloney murine leukemia virus (Mo-MuLV)-based retroviral vector expressing GFP. Transfection was evaluated by fluorescence microscopy and fluorescence-activated cell sorting. The rate of transfection of the primary cells was 33.4% for ECs, 48 hours after transfection. Stable transfection could be observed for at least 25 subsequent passages. Retroviral transfection with GFP enables stable and reliable long-term labeling of ovine ECs. This approach might offer an attractive pathway to study tissue development, with emphasis on distinguishing between cellular components initially seeded onto a construct and those occurring as a result of cell ingrowth from surrounding tissue.

Animals↗

PubMed2005

Vacancy engineered ceria nanostructures for protection from radiation-induced cellular damage.

The ability of engineered cerium oxide nanoparticles to confer radioprotection was examined. Human normal and tumor cells were treated with nanoceria and irradiated, and cell survival was measured. Treatment of normal cells conferred almost 99% protection from radiation-induced cell death, whereas the same concentration showed almost no protection of tumor cells. For the first time, nanoceria is shown to confer radioprotection to a normal human breast line but not to a human breast tumor line, MCF-7.

Apoptosis↗

PubMed2001

Growth factor delivery for bone tissue engineering.

Bone is a dynamic tissue that undergoes significant turnover during the life cycle of an individual. Despite having a significant regenerative capability, trauma and other pathological scenarios commonly require therapeutic intervention to facilitate the healing process. Bone tissue engineering, where cellular and biological processes at a site are deliberately manipulated for a therapeutic outcome, offers a viable option for the treatment of skeletal diseases. In this review paper, we aim to provide a brief synopsis of cellular and molecular basis of bone formation that are pertinent to current efforts of bone healing. Different approaches for engineering bone tissue were presented with special emphasis on the use of soluble (diffusible) therapeutic agents to accelerate bone healing. The latter agents have been used for both local bone repair (i.e. introduction of agents directly to a site of repair) as well as systemic bone regeneration (i.e. delivery for regeneration throughout the skeletal system). Critical drug delivery and targeting issues pertinent for each mode of bone regeneration are provided. In addition, future challenges and opportunities in bone tissue engineering are proposed from the authors' perspective.

Bone Morphogenetic Proteins↗

PubMed2006

Genetic parts to program bacteria.

Genetic engineering is entering a new era, where microorganisms can be programmed using synthetic constructs of DNA encoding logic and operational commands. A toolbox of modular genetic parts is being developed, comprised of cell-based environmental sensors and genetic circuits. Systems have already been designed to be interconnected with each other and interfaced with the control of cellular processes. Engineering theory will provide a predictive framework to design operational multicomponent systems. On the basis of these developments, increasingly complex cellular machines are being constructed to build specialty chemicals, weave biomaterials, and to deliver therapeutics.

Bacteria↗

PubMed2001

A tissue engineered cell-occlusive device for hard tissue regeneration--a preliminary report.

Tissue engineering is an emerging discipline that applies engineering principles to create devices for the study, restoration, modification, and assembly of functional tissues and organs from native or synthetic sources. In the field of guided bone regeneration (GBR), cellular matter engineering has been applied, more or less successfully, to the development of biodegradable and bioresorbable devices with chemical, physical, or mechanical properties, structure, or form that permit active tissue integration with desirable cell types and tissue components. The employment of synthetic and naturally occurring polymers as well as sophisticated manufacturing technologies allow the tissue engineering of matrix configurations so that the biophysical limitations of mass transfer can be satisfied. The configuration of such a hybrid matrix can also be manipulated to vary the surface area available for cell attachment, as well as to optimize the exposure of the attached cells to nutrients. A biodegradable and bioresorbable device made of synthetic and natural polymers was engineered specifically for GBR procedures. The degradation and resorption kinetics as well as the mechanical properties give the device the potential to function as a carrier for bone growth factors. This innovative device was applied as a GBR membrane in a clinical investigation in seven patients.

Absorbable Implants↗

PubMed2006

Compensation of endogenous IgG mediated inhibition of antibody-dependent cellular cytotoxicity by glyco-engineering of therapeutic antibodies.

A major limitation to the application of therapeutic IgG antibodies (Abs) is their reduced in vivo efficacy compared to their high efficacy as measured in vitro. Recently, Preithner et al. showed that the high amount of endogenous serum IgG impairs the antibody-dependent cellular cytotoxicity effector function (ADCC) of therapeutic Abs in vivo by competing for binding to Fcgamma-RIII on the effector cells. Modification of the glycosylation moieties attached to the Fc part of the Ab, e.g. de-fucosylation, has been shown to increase ADCC activity. We here show that the ADCC activity of a fucose-deficient, moss-produced therapeutic IgG is not impaired by normal human serum. The increased ADCC activity of the fucose-deficient Ab variant even in the presence of high endogenous IgG indicates that glyco-engineering of Abs may translate into improved clinical efficacy. Noteworthy, moss production of glyco-modified Abs should be applicable to a broad variety of therapeutic Abs currently in use indicative for the potential of this technology platform.

Antibodies, Monoclonal↗

PubMed2005

Targeting and inhibition of cell growth by an engineered dendritic nanodevice.

The cellular uptake and cytotoxicity of an engineered multifunctional dendritic nanodevice containing folic acid (FA) as the targeting molecule, methotrexate (MTX) as the chemotherapeutic drug, and fluorescein (FI) as the detecting agent were studied in vitro. FI and FA were conjugated to the generation 5 poly(amidoamine) (G5) dendrimer carrier through a thiourea and amide linkage and MTX was conjugated through an ester linkage to the carrier to generate the trifunctional dendritic device, G5-FI-FA-MTX. This trifunctional dendrimer-drug conjugate bound to FA receptor-expressing KB cells in a dose-dependent and saturable manner. Confocal microscopic analysis demonstrated cellular internalization of the conjugate. G5-FI-FA-MTX induced a time- and dose-dependent inhibition of cell growth in KB cells. The targeted dendrimer conjugates G5-FI-FA-MTX and G5-FA-MTX inhibited cell growth in KB cells, whereas the nontargeted G5-MTX failed to induce growth inhibition. These studies show the potential of G5-FI-FA-MTX or G5-FA-MTX for targeting and growth suppression of tumor cells that overexpress FA-receptors.

Antineoplastic Agents↗