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Bioengineering education in Canada, 1988.

As a companion article to the Journal of Clinical Engineering's series on Bioengineering Education in the United States, this paper describes the biomedical engineering and biomedical engineering technology programs in Canada. The purpose of the article is not to evaluate each program, but to illustrate the breadth of bioengineering and related programs available today in this country. While biomedical engineering technology programs are offered at the college level, the Canadian philosophy toward biomedical engineering is slightly different from that found in the United States: in Canada, biomedical engineering is offered only at the graduate level to qualified applicants with a previous degree in engineering, science, medicine, or dentistry.

Biomedical Engineering↗

Blood-contacting biomaterials: bioengineering viewpoints.

The investigation of blood-contacting biomaterials is an important challenge and is relevant for an improvement in the clinical application of biomaterials. With the purpose of improved clinical treatment, bioengineering viewpoints of blood-contacting biomaterials cover the material options and selection, the utilization of materials, the development of materials with better properties, and processing characteristics, and the design of relevant evaluation procedures. The bioengineering objective remains that of achieving an enhanced understanding of the relationship between a biomaterial and the biological response.

Biocompatible Materials↗

Proper statistical analysis of transepidermal water loss (TEWL) measurements in bioengineering studies.

In irritancy studies, measurement of transepidermal water loss (TEWL) is a widely used technique to assess barrier function. Using inappropriate statistical methods, however, leads to loss of information and misinterpretation of results. In this paper, we discuss some problems and pitfalls when using a suitable statistical technique for most designs in bioengineering studies, analysis of variance (ANOVA): multiple comparisons, choice of sample size and violation of statistical assumptions. For clarification of these points, a practical example will be given. Using the proposed adequate statistical methods correctly will, although accompanied by increased complexity, increase the efficiency of bioengineering studies.

Analysis of Variance↗

The National Institute of Biomedical Imaging and Bioengineering: history, status, and potential impact.

In December 2000, President Clinton signed legislation establishing the National Institute of Biomedical Imaging and Bioengineering (NIBIB). This action was the result of a multidecade effort of the biomedical imaging and engineering communities to gain increased recognition for biomedical imaging and engineering research within the National Institutes of Health and to enhance the impact of these disciplines on the health and well-being of people worldwide. Beginning in January 2001, several activities were initiated to form NIBIB into a real asset for researchers in biomedical imaging and engineering. These activities reflect a recognition that research in biomedical imaging and bioengineering has the potential of positively influencing research in many other biomedical disciplines, as well as directly affecting the welfare of people everywhere. This potential impact is discussed in this report, together with the history and present status of the formation of NIBIB.

Academies and Institutes↗

Biomedical device design discovery team approach to teaching physiology to undergraduate bioengineering students.

Teaching effectiveness is enhanced by generating student enthusiasm, by using active learning techniques, and by convincing students of the value of acquiring knowledge in the area of study. We have employed a technique to teach physiology to bioengineering students that couples students' enthusiasm for their chosen field, bioengineering, with an active learning process in which students are asked to design a biomedical device to enhance, replace, or create a new cellular or organ system function. Each assignment is designed with specific constraints that serve to direct students' attention to specific areas of study and that require students to create original designs. Preventing students from using existing designs spurred student invention and enthusiasm for the projects. Students were divided into groups or "design discovery teams" as might be done in a biomedical device industry setting. Students then researched the physiological issues that would need to be addressed to produce an acceptable design. Groups met with faculty to brainstorm and to obtain approval for their general design concepts before proceeding. Students then presented their designs to the instructors in a structured, written outline form and to the class as a 10-minute oral presentation. Grades were based on the outline, oral presentation, and peer evaluations (group members anonymously rated contributions of other members of their team). We believe that this approach succeeded in generating enthusiasm for learning physiology by allowing the students to think creatively in their chosen field of study and that it has resulted in students developing a more thorough understanding of difficult physiological concepts than would have been achieved with a traditional didactic lecture approach.

Animals↗

Assessment of 'dry skin': current bioengineering methods and test designs.

Dry skin is a frequent problem in dermatology and a sign of dysfunction of the epidermis, especially of the stratum corneum as the morphological equivalent of the skin barrier. It may occur as an individual disposition or as the leading symptom of atopic dermatitis or ichthyosis. Besides the visual examination of the skin, various bioengineering methods have been developed to assess the different pathological and adaptive changes in the skin. In addition to the assessment of skin humidity, barrier function and desquamation, the quantification of skin surface topography and the mechanical properties of skin are suitable methods to characterize a dry skin condition. For clinical assessment of moisturizing products and emollients the parameters of investigation have to be defined and integrated in an adapted study design depending on the composition and content of the active agent in the test product. Newly developed cosmetic products have to be investigated for safety and efficacy. Modern bioengineering methods are suitable to fulfill these challenges.

Animals↗

Improved left ventricular aneurysm repair with bioengineered vascular smooth muscle grafts.

BACKGROUND: Recurrent ventricular dilatation can occur after surgical repair of a left ventricular (LV) aneurysm. Use of an autologous bioengineered muscle graft to replace resected scar tissue may prevent recurrent dilatation and improve cardiac function. METHODS: Vascular smooth muscle cells (SMCs, 5 x 10(6) cells) from rat aortas were seeded onto synthetic PCLA (sponge polymer of epsilon-caprolactone-co-L-lactide reinforced with knitted poly-L-lactide fabric) patches and cultured for 2 weeks to allow tissue formation. Syngenic rats underwent proximal left coronary artery ligation to create a transmural myocardial scar. Four weeks after coronary ligation, cell-seeded patches (n=15) or unseeded patches (n=12) were used for a modified endoventricular circular patch plasty (EVCPP) repair of the infarct area. Ligated controls (n=14) and nonligated normal rats (n=10) had sham surgeries without EVCPP. Cardiac function was assessed by echocardiography and isolated Langendorff heart perfusion. Graft histology and morphology was also assessed. RESULTS: After 8 weeks in vivo, seeded patches were thicker (P<0.05) and smaller in area (P<0.003) than unseeded patches. Only seeded patches had prominent elastic tissue formation (P<0.001) in association with SMCs. LV systolic function by echocardiography was improved in the seeded group compared with both unseeded (P<0.002) and control groups (P<0.0001). LV volumes in both patch repair groups were comparable but were significantly smaller (P<0.05) than controls. LV distensibility tended toward improvement in the seeded group as compared with unseeded hearts, but the difference did not achieve statistical significance (P=0.06). CONCLUSIONS: Surgical repair with muscle-cell seeded grafts reduced abnormal chamber distensibility and improved LV function after myocardial infarction as compared with unseeded grafts. Bioengineered muscle grafts may be superior to synthetic materials for the surgical repair of LV scar.

Animals↗

Survival and function of bioengineered cardiac grafts.

INTRODUCTION: Patients with congenital heart disease frequently require graft material for repair of cardiac defects. However, currently available grafts lack growth potential and are noncontractile and thrombogenic. We have developed a viable cardiac graft that contracts spontaneously in tissue culture by seeding cells derived from fetal rat ventricular muscle into a biodegradable material. We report our investigations of the in vitro and in vivo survival and function of this bioengineered cardiac graft. METHODS AND RESULTS: A cardiomyocyte-enriched cell inoculum derived from fetal rat ventricular muscle was seeded into a piece of Gelfoam (Upjohn, Ontario, Canada), a biodegradable gelatin mesh, to form the graft. For in vitro studies, growth patterns of the cells within the graft were evaluated by constructing growth curves and by histologic examination; in in vivo studies, the graft was cultured for 7 days and then implanted either into the subcutaneous tissue of adult rat legs or onto myocardial scar tissue in a cryoinjured rat heart. Five weeks later, the graft was studied histologically. The inoculated cells attached to the gelatin mesh and grew in 3 dimensions in tissue culture, forming a beating cardiac graft. In both the subcutaneous tissue and the myocardial scar, blood vessels grew into the graft from the surrounding tissue. The graft implanted into the subcutaneous tissue contracted regularly and spontaneously. When implanted onto myocardial scar tissue, the cells within the graft survived and formed junctions with the recipient heart cells. CONCLUSIONS: Fetal rat ventricular cells can grow 3-dimensionally in a gelatin mesh. The cells in the graft formed cardiac tissue and survived and contracted spontaneously both in tissue culture and after subcutaneous implantation. Future versions of this bioengineered cardiac graft may eventually be used to repair cardiac defects.

Animals↗

Production of bioengineered cancer tissue constructs in vitro: epithelium-mesenchyme heterotypic interactions.

A few models have been established to study cancer cells in vitro. However, the cellular interactions have rarely been studied specifically using bioengineered cancer constructs combining human carcinoma cells and tumor-associated fibroblasts. We developed an in vitro model of tridimensional bioengineered cancer tissue constructs (bCTC) by seeding mammary epithelial cancer cells or normal keratinocytes over a mesenchymal layer containing tumor-derived fibroblastic cells or normal skin fibroblasts. After the introduction of epithelial cells, each construct was cultured for another 10 d. Histologic analyses showed that carcinoma cell lines could invade the subjacent mesenchymal layer and that the capacity to migrate was related to the invasive potential of cancer cells and the type of fibroblasts used, while noninvasive populations did not. Of the tested epithelial cells, MDA-MB-231 and, to a lesser degree, HDQ-P1 cell lines were invasive, and the invasion was deeper into the mesenchymal component containing tumor-derived fibroblasts. However, with normal skin fibroblasts, the mesenchymal layer was degraded twice faster than with tumor-derived fibroblastic cells. MDA-MB-231 cells and normal keratinocytes induced the highest level of gelatinase B, and the level was lowest with the MCF-7 cell line. The activated form of gelatinase B was, however, induced to the highest levels in the keratinocyte-seeded bCTC containing tumor-derived but not normal fibroblasts. MDA-MB-231 was the only epithelial cancer cell line whose activity of gelatinase A was reduced when cocultured with tumor-derived fibroblasts but not under normal fibroblast stimulation. Finally, a 50/48-kDa gelatinase band has been observed in bCTCs with noninvasive epithelial cells only. Our study demonstrates the selective secretion of gelatinases according to the phenotype of the cells seeded in the various bCTCs.

Breast↗

Fractional calculus in bioengineering.

Fractional calculus (integral and differential operations of noninteger order) is not often used to model biological systems. Although the basic mathematical ideas were developed long ago by the mathematicians Leibniz (1695), Liouville (1834), Riemann (1892), and others and brought to the attention of the engineering world by Oliver Heaviside in the 1890s, it was not until 1974 that the first book on the topic was published by Oldham and Spanier. Recent monographs and symposia proceedings have highlighted the application of fractional calculus in physics, continuum mechanics, signal processing, and electromagnetics, but with few examples of applications in bioengineering. This is surprising because the methods of fractional calculus, when defined as a Laplace or Fourier convolution product, are suitable for solving many problems in biomedical research. For example, early studies by Cole (1933) and Hodgkin (1946) of the electrical properties of nerve cell membranes and the propagation of electrical signals are well characterized by differential equations of fractional order. The solution involves a generalization of the exponential function to the Mittag-Leffler function, which provides a better fit to the observed cell membrane data. A parallel application of fractional derivatives to viscoelastic materials establishes, in a natural way, hereditary integrals and the power law (Nutting/Scott Blair) stress-strain relationship for modeling biomaterials. In this review, I will introduce the idea of fractional operations by following the original approach of Heaviside, demonstrate the basic operations of fractional calculus on well-behaved functions (step, ramp, pulse, sinusoid) of engineering interest, and give specific examples from electrochemistry, physics, bioengineering, and biophysics. The fractional derivative accurately describes natural phenomena that occur in such common engineering problems as heat transfer, electrode/electrolyte behavior, and sub-threshold nerve propagation. By expanding the range of mathematical operations to include fractional calculus, we can develop new and potentially useful functional relationships for modeling complex biological systems in a direct and rigorous manner.

Action Potentials↗

Fractional calculus in bioengineering, part 2.

Fractional calculus (integral and differential operations of noninteger order) is not often used to model biological systems. Although the basic mathematical ideas were developed long ago by the mathematicians Leibniz (1695), Liouville (1834), Riemann (1892), and others and brought to the attention of the engineering world by Oliver Heaviside in the 1890s, it was not until 1974 that the first book on the topic was published by Oldham and Spanier. Recent monographs and symposia proceedings have highlighted the application of fractional calculus in physics, continuum mechanics, signal processing, and electromagnetics, but with few examples of applications in bioengineering. This is surprising because the methods of fractional calculus, when defined as a Laplace or Fourier convolution product, are suitable for solving many problems in biomedical research. For example, early studies by Cole (1933) and Hodgkin (1946) of the electrical properties of nerve cell membranes and the propagation of electrical signals are well characterized by differential equations of fractional order. The solution involves a generalization of the exponential function to the Mittag-Leffler function, which provides a better fit to the observed cell membrane data. A parallel application of fractional derivatives to viscoelastic materials establishes, in a natural way, hereditary integrals and the power law (Nutting/Scott Blair) stress-strain relationship for modeling biomaterials. In this review, I will introduce the idea of fractional operations by following the original approach of Heaviside, demonstrate the basic operations of fractional calculus on well-behaved functions (step, ramp, pulse, sinusoid) of engineering interest, and give specific examples from electrochemistry, physics, bioengineering, and biophysics. The fractional derivative accurately describes natural phenomena that occur in such common engineering problems as heat transfer, electrode/electrolyte behavior, and sub-threshold nerve propagation. By expanding the range of mathematical operations to include fractional calculus, we can develop new and potentially useful functional relationships for modeling complex biological systems in a direct and rigorous manner. In Part 1 of this review (Crit Rev Biomed Eng 2004; 32(1):1-104), the fundamental properties of fractional calculus were introduced. The reader should refer to that material, particularly the sections on special functions and fractional order differential equations, for background.

Action Potentials↗

A bioengineered implant for a predetermined bone cellular response to loading forces. A literature review and case report.

The presence of fibrous tissue has long been known to decrease the long-term survival of a root-form implant. Excessive loads on an osseointegrated implant may result in mobility of the supporting device, and excessive loads may also fracture an implant component or body. Although several conditions may cause crestal bone loss, one of these may be prosthetic overload. Excessive loads on the bone cause strain conditions to increase. These microstrains on the bone may affect the bone remodeling rate in a direct relationship. When strain conditions to the interfacial bone are in the mild overload zone, an increased bone remodeling response occurs, which results in a reactive woven bone formation that is less mineralized and weaker. Greater stresses may cause the interfacial strain to reach the pathologic overload zone and may cause microfracture of the bone, fibrous tissue formation, and/or bone resorption. Recent reports suggest that the bone remodeling rate next to an implant may be used to evaluate biomechanical conditions and their influence on the implant-to-bone interface. These include a number of factors, such as loading conditions, implant body surface conditions, and implant design. For a given load condition, the implant design is one of the primary factors that determine the resultant strain at the interface. A predetermined goal was established to bioengineer a dental implant to load the bone at the interface in a predetermined stress strain relationship, in order to maintain lamellar bone at the interface. A case report is presented of 2 bioengineered implants loaded for 1 year, which demonstrates that the bone was primarily lamellar in structure, the bone turnover rate was less than 5 microns/day, and was the same as the bone away from the interface. These findings corroborate those observed in a prior animal study reported with the same implant design. Although the number of implants evaluated in those 2 reports is few, they support a predetermined histological outcome.

Adult↗

Use of subatmospheric (VAC) therapy to improve bioengineered tissue grafting in diabetic foot wounds.

The use of bioengineered tissue and topical subatmospheric pressure therapy have both been widely accepted as adjunctive therapies for the treatment of noninfected, nonischemic diabetic foot wounds. This article describes a temporally overlapping method of care that includes a period of simultaneous application of bioengineered tissue (Apligraf, Novartis Pharmaceuticals Corp, East Hanover, New Jersey) and subatmospheric pressure therapy delivered through the VAC (Vacuum Assisted Closure) system (KCI, Inc, San Antonio, Texas). Future descriptive and analytic works may test the hypothesis that combined therapies used at different and often overlapping periods during the wound-healing cycle may be more effective than a single modality.

Bandages↗

[Some bioengineering and hygienic aspects of incorporating sodium light illuminators into space life support systems].

Some bioengineering aspects of utilizating high-pressure sodium lamps (HPSL) in space plant growth chambers are reviewed. Comparative feasibility analysis of various lighting systems currently used in plant industry, and investigation of HPSL limitations and advantages allow the conclusion about their good prospect as a component of future plant growth facilities aboard long-term space bioengineering life support systems. High appraisal is given to the design of a board prototype of the DnaTSf-70 sodium lamp. Associated sanitary-hygienic regulations developed, HPSL are liable to be also used to lighten the spacecraft interior.

Biomedical Engineering↗

Ethical considerations in bioengineering research.

Biomedical science and engineering have made rapid advancements in the field of medicine over the past few decades. New ethical problems arising from this technology are influencing biomedical research more and more. It is disturbing that bioengineering professionals have had relatively little contact with moral and legal theory in light of these developments and particularly since they represent the forefront of new medical innovations. The objective of this communication is to introduce the study of bioethics and the use of principlism when examining bioengineering problems and dilemmas. Specific examples derived from actual proceedings, such as the Baltimore case, will alert scientists to the importance of misconduct in academic society. Cases will be used to illustrate how tools learned in this presentation are applied to analyze bioethical issues. New technology has a large social impact and is setting the standard of care for treatment. The health care system continually relies on researchers to produce improvements in patient therapy. Society will increasingly expect scientists to be morally responsible for the research they perform and uphold those virtues that ensure good ethical conduct.

Biomedical Engineering↗

Symbiosis: nursing and the bioengineer.

At this time, bioinstrumentation is the product of the possible as modified by what is practical. The bioengineer offers both the possible and the practical from an engineering and ideal model. The nurse, in contrast, speaks to the ideal possible from a confining practical clinical model. Symbiosis of nursing and bioengineering will combine the important attributes of each discipline for the betterment of patient care. In truth, the machine becomes an instrument of humanity.

Biomedical Engineering↗

Bioengineering principles of hydrotherapy.

Hydrotherapy is based on several important bioengineering principles that permit the design and development of aquatic exercise devices, techniques and programs. These principles involve several forces (buoyancy, drag, inertia), hydrostatic pressure and the specific heat of water. By acquiring a knowledge of these bioengineering principles, an individualized exercise program can be prescribed that will enhance physical fitness which is associated with desirable psychological changes.

Biomechanical Phenomena↗

A voyage of reprogrammable metabolic bioengineering reshapes plant defense: from editing tools to synthetic systems.

Metabolic bioengineering has emerged as a transformative approach for reshaping plant defense by targeting intrinsic biosynthetic pathways to enhance immunity in modern agriculture. Moving beyond proof-of-concept metabolomics to broad-spectrum programmable pathway engineering addresses gaps in plant rational design and optimizes resilience in response to diverse environmental cues. This review aims to comprehensively highlight the transition of innovative approaches to phenolics, alkaloids, flavonoids, terpenoids, and benzoxazinoids, inferring adaptive reprogramming that mediates the growth-defense balance and functions as molecular sentinels in plants. Furthermore, decoding the volatile metabolome reveals a dynamic signaling interface that influences defense responses and stress-induced plant-microbe interactions, with the shikimate, jasmonate, and salicylate pathways functioning as central hubs for microbial deterrence and priming immune memory. Recent developments in multi-scalar genome-editing strategies, including CRISPR-driven combinatorial edits, enzyme orthogonalization, fluxomics, and spatially resolved multi-omics, reconfigure central and specialized metabolic fluxes toward improved defense function and regulation. Additionally, emerging tools, such as WUSCHEL2 and BABY BOOM transcriptional modules, and artificial engineering strategies integrating deep learning model-driven predictions facilitate rapid development of synthetic genetic circuits and support a predictive engineering of plants. Moreover, Mass spectrometry imaging (MSI) in spatial metabolomics enables to obtain structures and locations of unidentified endogenous metabolites within cells and tissues. Overall, this review emphasizes a diverse array of primary and secondary metabolites, spanning molecular concepts to recent advances in plant immune mechanisms. It also illustrates new frontiers in programmable metabolic engineering that accelerate the understanding of plant-microbe-metabolite cross-talks, offering strategies to improve plant resistance and advance sustainable agricultural solutions.

metabolic bioengineering↗