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PubMed1999

Antigen presentation pathways for immunity to islet transplants. Relevance to immunoisolation.

Tremendous advances have been made over the past several years in the development of diverse biocompatible materials and structural designs for the implantation of immunoisolated cells and tissues. This area of bioengineering has clear application to insulin-dependent diabetes for which the implantation of micro- or macroencapsulated pancreatic islets or surrogate beta cells has great potential therapeutic benefit. This discussion concentrates on three antigen-specific immunologic processes that impede the application of islet transplantation as a therapy for insulin-dependent diabetes: (1) Allograft immunity, (2) Xenograft immunity, and (3) Autoimmune pathogenesis of Type I diabetes. Special emphasis is placed on the potential impact of these immune pathways on immunoisolated tissues.

Animals↗

PubMed2002

Tissue engineering and reparative medicine.

Reparative medicine is a critical frontier in biomedical and clinical research. The National Institutes of Health Bioengineering Consortium (BECON) convened a symposium titled "Reparative Medicine: Growing Tissues and Organs," which was held on June 25 and 26, 2001 in Bethesda, Maryland. The relevant realms of cells, molecular signaling, extracellular matrix, engineering design principles, vascular assembly, bioreactors, storage and translation, and host remodeling and the immune response that are essential to tissue engineering were discussed. This overview of the scientific program summarizes the plenary talks, extended poster presentations and breakout session reports with an emphasis on scientific and technical hurdles that must be overcome to achieve the promise of restoring, replacing, or enhancing tissue and organ function that tissue engineering offers.

Animals↗

PubMed2025

Genome editing in the green alga Chlamydomonas: past, present practice and future prospects.

The green alga Chlamydomonas is an important and versatile model organism for research topics ranging from photosynthesis and metabolism, cilia, and basal bodies to cellular communication and the cellular cycle and is of significant interest for green bioengineering processes. The genome in this unicellular green alga is contained in 17 haploid chromosomes and codes for 16 883 protein coding genes. Functional genomics, as well as biotechnological applications, rely on the ability to remove, add, and change these genes in a controlled and efficient manner. In this review, the history of gene editing in Chlamydomonas is put in the context of the wider developments in genetics to demonstrate how many of the key developments to engineer these algae follow the global trends and the availability of technology. Building on this background, an overview of the state of the art in Chlamydomonas engineering is given, focusing primarily on the practical aspects while giving examples of recent applications. Commonly encountered Chlamydomonas-specific challenges, recent developments, and community resources are presented, and finally, a comprehensive discussion on the emergence and evolution of CRISPR/Cas-based precision gene editing is given. An outline of possible future paths for gene editing based on current global trends in genetic engineering and tools for gene editing is presented.

Gene Editing↗

PubMed2004

Computational physiology and the Physiome Project.

Bioengineering analyses of physiological systems use the computational solution of physical conservation laws on anatomically detailed geometric models to understand the physiological function of intact organs in terms of the properties and behaviour of the cells and tissues within the organ. By linking behaviour in a quantitative, mathematically defined sense across multiple scales of biological organization--from proteins to cells, tissues, organs and organ systems--these methods have the potential to link patient-specific knowledge at the two ends of these spatial scales. A genetic profile linked to cardiac ion channel mutations, for example, can be interpreted in relation to body surface ECG measurements via a mathematical model of the heart and torso, which includes the spatial distribution of cardiac ion channels throughout the myocardium and the individual kinetics for each of the approximately 50 types of ion channel, exchanger or pump known to be present in the heart. Similarly, linking molecular defects such as mutations of chloride ion channels in lung epithelial cells to the integrated function of the intact lung requires models that include the detailed anatomy of the lungs, the physics of air flow, blood flow and gas exchange, together with the large deformation mechanics of breathing. Organizing this large body of knowledge into a coherent framework for modelling requires the development of ontologies, markup languages for encoding models, and web-accessible distributed databases. In this article we review the state of the field at all the relevant levels, and the tools that are being developed to tackle such complexity. Integrative physiology is central to the interpretation of genomic and proteomic data, and is becoming a highly quantitative, computer-intensive discipline.

Biophysical Phenomena↗

PubMed2003

An advanced approach for computer modeling and prototyping of the human tooth.

This paper presents a systematic and practical method for constructing accurate computer and physical models that can be employed for the study of human tooth mechanics. The proposed method starts with a histological section preparation of a human tooth. Through tracing outlines of the tooth on the sections, discrete points are obtained and are employed to construct B-spline curves that represent the exterior contours and dentino-enamel junction (DEJ) of the tooth using a least square curve fitting technique. The surface skinning technique is then employed to quilt the B-spline curves to create a smooth boundary and DEJ of the tooth using B-spline surfaces. These surfaces are respectively imported into SolidWorks via its application protocol interface to create solid models. The solid models are then imported into Pro/MECHANICA Structure for finite element analysis (FEA). The major advantage of the proposed method is that it first generates smooth solid models, instead of finite element models in discretized form. As a result, a more advanced p-FEA can be employed for structural analysis, which usually provides superior results to traditional h-FEA. In addition, the solid model constructed is smooth and can be fabricated with various scales using the solid freeform fabrication technology. This method is especially useful in supporting bioengineering applications, where the shape of the object is usually complicated. A human maxillary second molar is presented to illustrate and demonstrate the proposed method. Note that both the solid and p-FEA models of the molar are presented. However, comparison between p- and h-FEA models is out of the scope of the paper.

Anatomy, Cross-Sectional↗

PubMed2001

The surface-tension-driven flow of blood from a droplet into a capillary tube.

In tissue, medical, or dental engineering, when blood comes into contact with a new artificial material, the flow may be influenced by surface tension between the blood and the surface of the material. The effect of surface tension on the flow of blood is significant, especially in microscale. The leading edge of the flowing blood is the triple point where the blood, the material surface, and a stationary gas orfluid meet. The movement of the triple point, i.e., the advancing front of the flow, is driven by surface tension, resisted by viscous shear stress, and balanced by the inertial force (-mass x acceleration). In this article, the dynamics is illustrated in detail in the case of blood flowing into a capillary tube by contact. The capillar, tube draws the blood into it. It is shown theoretically that initially the flow of blood in the capillary has a large acceleration, followed by a relatively large deceleration over the next short period of time, then the acceleration becomes small and oscillatory. The velocity history appears impulsive at first, then slows down. The history of the length of blood column appears smooth after integration. Existing solutions of the Navier-Stokes equation permit the analysis of simpler cases. Further fluid mechanics development is needed to meet the practical needs of bioengineering. The importance of experimental study of surface tension and contact angle over a biological surface or a man-made material as a future direction of research is pointed out.

Biomechanical Phenomena↗

PubMed2005

Computational studies of shape memory alloy behavior in biomedical applications.

BACKGROUND: Nowadays, shape memory alloys (SMAs) and in particular Ni-Ti alloys are commonly used in bioengineering applications as they join important qualities as resistance to corrosion, biocompatibility, fatigue resistance, MR compatibility, kink resistance with two unique thermo-mechanical behaviors: the shape memory effect and the pseudoelastic effect. They allow Ni-Ti devices to undergo large mechanically induced deformations and then to recover the original shape by thermal loading or simply by mechanical unloading. METHOD OF APPROACH: A numerical model is developed to catch the most significant SMA macroscopic thermo-mechanical properties and is implemented into a commercial finite element code to simulate the behavior of biomedical devices. RESULTS: The comparison between experimental and numerical response of an intravascular coronary stent allows to verify the model suitability to describe pseudo-elasticity. The numerical study of a spinal vertebrae spacer where the effects of different geometries and material characteristic temperatures are investigated, allows to verify the model suitability to describe shape memory effect. CONCLUSION: the results presented show the importance of computational studies in designing and optimizing new biomedical devices.

Alloys↗

PubMed1991

Endothelialization of the luminal sac in artificial cardiac prostheses: a challenge for both biologists and engineers.

Thromboembolic complications are a major obstacle for the permanent use of artificial cardiac prostheses. Many of these complications are caused by the intrinsic thrombogenicity of the biomaterials, which are used to cast the luminal blood sac. Numerous attempts have been made to improve the hemocompatibility of the new generation of totally implantable blood pumps, mainly by physico-chemical modifications of the biopolymeric materials and the blood contacting surfaces. We, on the other hand, believe that the most promising and challenging approach, from both the biologists' and engineers' point of view, is to coat the luminal surfaces of cardiac prostheses with a functional monolayer of autologous endothelial cells (ECs) and thus reproduce "nature's biocompatible blood container." The key to lining an artificial heart with a nonthrombogenic monolayer of endothelial cells is to explore the molecular and cellular mechanisms which render the EC lining inside the beating ventricle nonthrombogenic and resistant to flow-induced shear stresses and cyclic, tensional deformations. This knowledge has then to be translated into biotechnological know-how, in order to maintain an intact EC monolayer inside the blood sac of an artificial device. In this paper we emphasize some of the bioengineering issues associated with the endothelialization of the luminal sac, and also discuss some aspects related to the blood sac itself.

Biocompatible Materials↗

PubMed1987

A theoretical model for water flux through the artery wall.

A two layer model for water flux through the artery is studied using a mathematical model based on the theory for the consolidation of water saturated soils. The matrix is considered to be constituted by two layers with different permeabilities and different elastic constants and the two systems of equations are coupled with the condition of continuity of pressure, total stress, solid displacement and fluid seepage velocity at the interface. The luminal pressure is considered to be harmonic in time. Exact solutions are obtained for displacements and pressures in both the layers. For large consolidation times, large pressure gradients are found to exist near the boundaries and at the interface. The heterogeneous model may not only be useful to understand the mechanics of transport in the physiological system but it will also help the bioengineers to choose proper implant materials to design artificial vascular organs for the purpose of prosthesis.

Arteries↗

PubMedDate not supplied

Optical imaging in microfluidic bioreactors enables oxygen monitoring for continuous cell culture.

For the first time, a fluorescence lifetime calibration method for an oxygen-sensitive dye ruthenium tris(2,2'-dipyridyl) dichloride hexahydrate (RTDP) is applied to image oxygen levels in poly(dimethyl siloxane) (PDMS) bioreactors containing living C2C12 mouse myoblasts. PDMS microsystems are broadly used in bioengineering applications due to their biocompatibility and ease of handling. For these systems, oxygen concentrations are of significance and are likely to play an important role in cell behavior and gene expression. Fluorescence lifetime imaging microscopy (FLIM) bases image contrast on fluorophore excited state lifetimes, which reflect local biochemistry. Unique attributes of the widefield, time-domain FLIM system include tunable excitation (337.1 to 960 nm), large temporal dynamic range (> or =600 ps), high spatial resolution (1.4 microm), calibrated detection (0 to 300+/-8 microM of oxygen), and rapid data acquisition and processing times (10 s). Oxygen levels decrease with increasing cell densities and are consistent with model outcomes obtained by simulating bioreactor oxygen diffusion and cell proliferation. In single bioreactor loops, FLIM detects spatial heterogeneity in oxygen levels with variations as high as 20%. The fluorescence lifetime-based imaging approach we describe avoids intensity-based artifacts (including photobleaching and concentration variations) and provides a technique with high spatial discrimination for oxygen monitoring in continuous cell culture systems.

Animals↗

PubMed2002

Repairing the injured spinal cord.

Certain cell, molecular, and bioengineering strategies for repairing the injured spinal cord are showing encouraging results (either alone or in combination) in animal models, with limited recovery of mobility being reported in some cases.

Animals↗

PubMed2006

Enzyme-free nucleic acid logic circuits.

Biological organisms perform complex information processing and control tasks using sophisticated biochemical circuits, yet the engineering of such circuits remains ineffective compared with that of electronic circuits. To systematically create complex yet reliable circuits, electrical engineers use digital logic, wherein gates and subcircuits are composed modularly and signal restoration prevents signal degradation. We report the design and experimental implementation of DNA-based digital logic circuits. We demonstrate AND, OR, and NOT gates, signal restoration, amplification, feedback, and cascading. Gate design and circuit construction is modular. The gates use single-stranded nucleic acids as inputs and outputs, and the mechanism relies exclusively on sequence recognition and strand displacement. Biological nucleic acids such as microRNAs can serve as inputs, suggesting applications in biotechnology and bioengineering.

Animals↗

PubMed1998

Reversible hydrogels from self-assembling artificial proteins.

Recombinant DNA methods were used to create artificial proteins that undergo reversible gelation in response to changes in pH or temperature. The proteins consist of terminal leucine zipper domains flanking a central, flexible, water-soluble polyelectrolyte segment. Formation of coiled-coil aggregates of the terminal domains in near-neutral aqueous solutions triggers formation of a three-dimensional polymer network, with the polyelectrolyte segment retaining solvent and preventing precipitation of the chain. Dissociation of the coiled-coil aggregates through elevation of pH or temperature causes dissolution of the gel and a return to the viscous behavior that is characteristic of polymer solutions. The mild conditions under which gel formation can be controlled (near-neutral pH and near-ambient temperature) suggest that these materials have potential in bioengineering applications requiring encapsulation or controlled release of molecular and cellular species.

Amino Acid Sequence↗

PubMed2000

NIH. Imaging institute picks up momentum.

Last week a House panel approved the creation of the National Institute of Biomedical Imaging and Bioengineering (NIBIE) despite pleas from top National Institutes of Health officials that such a move will balkanize research. The bipartisan proposal, which is also backed by Democratic presidential candidate Al Gore, may have enough momentum to sail through Congress by the time it adjourns early next month. Even if it falls short, NIBIE reflects the growing desire of segments of the biomedical community to have their own address on the Bethesda campus.

Biomedical Engineering↗

PubMed2000

U.K. science budget. Gene jocks, data crunchers hit jackpot.

Unveiling its science spending plan for the next 3 years, the U.K. government last week announced major new investments in three key areas: tracking disease genes, leveraging the Internet for data analysis, and supporting emerging industries such as nanotechnology and bioengineering. Although these programs cut across a range of disciplines funded by the U.K.'s science councils, the government also bestowed a long-anticipated gift on astronomers: membership in the European Southern Observatory, which will give U.K. researchers access to the world's largest optical telescope.

Budgets↗

PubMed1986

Loops in globular proteins: a novel category of secondary structure.

The protein loop, a novel category of nonregular secondary structure, is a segment of contiguous polypeptide chain that traces a "loop-shaped" path in three-dimensional space; the main chain of an idealized loop resembles a Greek omega (omega). A systematic study was made of 67 proteins of known structure revealing 270 omega loops. Although such loops are typically regarded as "random coil," they are, in fact, highly compact substructures and may also be independent folding units. Loops are almost invariably situated at the protein surface where they are poised to assume important roles in molecular function and biological recognition. They are often observed to be modules of evolutionary exchange and are also natural candidates for bioengineering studies.

Protein Conformation↗

PubMed2005

Meeting report: the future and limits of systems biology.

Systems biology has enjoyed explosive growth in both the number of people participating in this area of research and the number of publications on the topic. And yet, the paradigms that underlie the field have not seen a similar expansiveness. Instead, most of these paradigms have been carried over from other fields like engineering, physics, and mathematics. As a result, a small set of concepts dominate the field. The traditional biologist is seen by many as outmoded and tolerated only as a source of data. In this view, the biologist's ideas may even be considered conceptually and theoretically irrelevant. In this Perspective, we take a critical look at some of the paradigms of systems biology and question whether the biologist's ideas, methods, and theories have really become outmoded. We see the future of systems biology as a tight coupling of in vivo and in vitro methods for bioengineering with in silico multicellular modeling and simulation.

Computational Biology↗

PubMed2005

Interferon alfacon-1 protects hamsters from lethal pichinde virus infection.

Hemorrhagic fever of arenaviral origin is a frequently fatal infectious disease of considerable priority to the biodefense mission. Historically, the treatment of arenaviral infections with alpha interferons has not yielded favorable results. Here we present evidence that interferon alfacon-1, a nonnaturally occurring bioengineered alpha interferon approved for the treatment of chronic hepatitis C, is active against Pichinde and Tacaribe arenaviruses in cell culture. In the hamster model of Pichinde virus (PCV) infection, interferon alfacon-1 treatment significantly protected animals from death, prolonged the survival of those that eventually died, reduced virus titers, and limited liver damage characteristic of PCV-induced disease. Moreover, interferon alfacon-1 also demonstrated therapeutic activity, to a lesser degree, when the initiation of treatment was delayed up to 2 days post-virus challenge. Despite the observed advantages of interferon alfacon-1 therapy, efforts to stimulate the immune system with the known interferon inducer poly(I:C12U) (Ampligen) offered only limited protection against lethal PCV challenge. Taken together, these data suggest that the increased potency of the bio-optimized interferon alfacon-1 molecule may be critical to the observed antiviral effects. These data are the first report demonstrating efficacious treatment of acute arenaviral disease with alpha interferon therapy, and further study is warranted.

Animals↗