A new paradigm for graduate research and training in the biomedical sciences and engineering

98Emphasis on the individual investigator has fostered discovery for centuries, yet it is now recognized that the complexity of problems in the biomedical sciences and engineering requires collaborative efforts from individuals having diverse training and expertise. Various approaches can facilitate interdisciplinary interactions, but we submit that there is a critical need for a new educational paradigm for the way that we train biomedical engineers, life scientists, and mathematicians. We cannot continue to train graduate students in isolation within single disciplines, nor can we ask any one individual to learn all the essentials of biology, engineering, and mathematics. We must transform how students are trained and incorporate how real-world research and development are done-in diverse, interdisciplinary teams. Our fundamental vision is to create an innovative paradigm for graduate research and training that yields a new generation of biomedical engineers, life scientists, and mathematicians that is more diverse and that embraces and actively pursues a truly interdisciplinary, team-based approach to research based on a known benefit and mutual respect. In this paper, we describe our attempt to accomplish this via focused training in biomechanics, biomedical optics, mathematics, mechanobiology, and physiology. The overall approach is applicable, however, to most areas of biomedical research.     

Digital game design-based STEM activity: Biodiversity example

Abstract

The purpose of this study is to design a digital game design-based STEM activity for fifth-grade students learning about endangered organisms and significance of biodiversity for living. This activity was carried out with twenty students in a public school in Eastern Black Sea Region of Turkey during academic year of 2018–2019 spring term. This study planned as eight-lesson time (8?×?40?minutes) and completed at this lesson time. The students were given the digital game design challenge in real-life problem context that has been created based on design-based science learning and for which they shall use their knowledge and skills in each of the STEM disciplines. During this design challenge, students worked like a scientist and an engineer. They carried out scientific research and inquiry process in the science discipline, understood the engineering design process in the engineering discipline, established mathematical relations in the mathematics discipline, learned how to make coding in the technology discipline, and used this knowledge and skills thus acquired in their suggested solutions for the design challenge. They designed a digital game by coding and presented science knowledge and skills that acquired from inquiry process.     

Design and integration of a problem-based biofabrication course into an undergraduate biomedical engineering curriculum

Background

The rapidly evolving discipline of biological and biomedical engineering requires adaptive instructional approaches that teach students to target and solve multi-pronged and ill-structured problems at the cutting edge of scientific research. Here we present a modular approach to designing a lab-based course in the emerging field of biofabrication and biological design, leading to a final capstone design project that requires students to formulate and test a hypothesis using the scientific method.

Results

Students were assessed on a range of metrics designed to evaluate the format of the course, the efficacy of the format for teaching new topics and concepts, and the depth of the contribution this course made to students training for biological engineering careers. The evaluation showed that the problem-based format of the course was well suited to teaching students how to use the scientific method to investigate and uncover the fundamental biological design rules that govern the field of biofabrication.

Conclusions

We show that this approach is an efficient and effective method of translating emergent scientific principles from the lab bench to the classroom and training the next generation of biological and biomedical engineers for careers as researchers and industry practicians.

     

A Simulation Tool for Industrial Ecology: Creating a Board Game

This article presents a board game that was developed for use as a simulation tool in teaching the basic concepts of industrial ecology (IE). The game, with the automobile industry as its theme, includes realistic numbers and displays a variety of IE principles. The objectives of the simulation, however, transcend the automobile industry and apply to other manufacturing industries. They include: pollution prevention, design for environment (in several forms, including design for disassembly), environmental management, and life-cycle assessment. The game has already been played by engineering and business professors, graduate students in environmental engineering, government representatives, and industry executives. A statistical analysis performed on pre- and post-game questionnaires indicates that the game is an effective teaching tool.     

A novel approach to physiology education for biomedical engineering students

It is challenging for biomedical engineering programs to incorporate an indepth study of the systemic interdependence of cells, tissues, and organs into the rigorous mathematical curriculum that is the cornerstone of engineering education. To be sure, many biomedical engineering programs require their students to enroll in anatomy and physiology courses. Often, however, these courses tend to provide bulk information with only a modicum of live tissue experimentation. In the Electrical, Computer, and Biomedical Engineering Department of the University of Rhode Island, this issue is addressed to some extent by implementing an experiential physiology laboratory that addresses research in electrophysiology and biomechanics. The two-semester project-based course exposes the students to laboratory skills in dissection, instrumentation, and physiological measurements. In a novel approach to laboratory intensive learning, the course meets on six Sundays throughout the semester for an 8-h laboratory period. At the end of the course, students are required to prepare a two-page conference paper and submit the results to the Northeast Bioengineering Conference (NEBC) for consideration. Students then travel to the conference location to present their work. Since the inception of the course in the fall of 2003, we have collectively submitted 22 papers to the NEBC. This article will discuss the nature of the experimentation, the types of experiments performed, the goals of the course, and the metrics used to determine the success of the students and the research.     

Biocompatibility of hydrogel-based scaffolds for tissue engineering applications

Recently, understanding of the extracellular matrix (ECM) has expanded rapidly due to the accessibility of cellular and molecular techniques and the growing potential and value for hydrogels in tissue engineering. The fabrication of hydrogel-based cellular scaffolds for the generation of bioengineered tissues has been based on knowledge of the composition and structure of ECM. Attempts at recreating ECM have used either naturally-derived ECM components or synthetic polymers with structural integrity derived from hydrogels. Due to their increasing use, their biocompatibility has been questioned since the use of these biomaterials needs to be effective and safe. It is not surprising then that the evaluation of biocompatibility of these types of biomaterials for regenerative and tissue engineering applications has been expanded from being primarily investigated in a laboratory setting to being applied in the multi-billion dollar medicinal industry. This review will aid in the improvement of design of non-invasive, smart hydrogels that can be utilized for tissue engineering and other biomedical applications. In this review, the biocompatibility of hydrogels and design criteria for fabricating effective scaffolds are examined. Examples of natural and synthetic hydrogels, their biocompatibility and use in tissue engineering are discussed. The merits and clinical complications of hydrogel scaffold use are also reviewed. The article concludes with a future outlook of the field of biocompatibility within the context of hydrogel-based scaffolds.     

Electromagnetic interference can cause hospital devices to malfunction,McGill group warns.

Electromagnetic interference (EMI) from sources such as television transmitters, police radios and cellular phones can cause medical monitors and other hospital devices to malfunction, says the principal investigator of a McGill biomedical engineering group set up in 1989 to study, predict and prevent such problems. The impact of equipment malfunction can range from mere inconvenience to serious problems. The research group advises physicians and other health care professionals to learn how to spot problems related to EMI and electromagnetic compatibility.     

Polylactic acid: synthesis and biomedical applications

Social and economic development has driven considerable scientific and engineering efforts on the discovery, development and utilization of polymers. Polylactic acid (PLA) is one of the most promising biopolymers as it can be produced from nontoxic renewable feedstock. PLA has emerged as an important polymeric material for biomedical applications on account of its properties such as biocompatibility, biodegradability, mechanical strength and process ability. Lactic acid (LA) can be obtained by fermentation of sugars derived from renewable resources such as corn and sugarcane. PLA is thus an eco-friendly nontoxic polymer with features that permit use in the human body. Although PLA has a wide spectrum of applications, there are certain limitations such as slow degradation rate, hydrophobicity and low impact toughness associated with its use. Blending PLA with other polymers offers convenient options to improve associated properties or to generate novel PLA polymers/blends for target applications. A variety of PLA blends have been explored for various biomedical applications such as drug delivery, implants, sutures and tissue engineering. PLA and their copolymers are becoming widely used in tissue engineering for function restoration of impaired tissues due to their excellent biocompatibility and mechanical properties. The relationship between PLA material properties, manufacturing processes and development of products with desirable characteristics is described in this article. LA production, PLA synthesis and their applications in the biomedical field are also discussed.     

生物医学工程的研究范围

“生物医学工程”这个词汇蕴含了三个专业领域的相互影响：生物学（最广义的范围讲是基于物理学和化学的一门基础科学）、医学（治疗疾病的科学）和工程学（设计及建造对人类有用的物品的科学）。在20世纪50年代中期,我被任命组建一个实验室,这个实验室需要结合这三大学科,并致力于听觉研究。在过去的50年中,我们的实验室（由麻省理工大学、哈佛大学、麻省总医院及麻省眼耳医院共同管理）树立了一个优秀的范例,证明虽然有一些实际的困难,科学家、临床医师和工程师们仍然可以很好地合作。我们的经验之一是,往往一些最成功的发现是基于对基本科学知识的发展,而不是来源于对特定临床需要的靶向性研究。然而,“研究与发展”常常需要有技术创新教育背景,并能与数个领域的专家充分交流的特殊工作人员。因此,在目前这个环境与社会问题需要传统意义上非生物医学工程领域的技术专家的时代,生物医学工程师的培养问题及资源应如何在发达国家与发展中国家之间分配的问题的探讨,都具有十分重要的现实意义。     

Biotechnology apprenticeship for secondary-level students: teaching advanced cell culture techniques for research

The purpose of this article is to discuss small-group apprenticeships (SGAs) as a method to instruct cell culture techniques to high school participants. The study aimed to teach cell culture practices and to introduce advanced imaging techniques to solve various biomedical engineering problems. Participants designed and completed experiments using both flow cytometry and laser scanning cytometry during the 1-month summer apprenticeship. In addition to effectively and efficiently teaching cell biology laboratory techniques, this course design provided an opportunity for research training, career exploration, and mentoring. Students participated in active research projects, working with a skilled interdisciplinary team of researchers in a large research institution with access to state-of-the-art instrumentation. The instructors, composed of graduate students, laboratory managers, and principal investigators, worked well together to present a real and worthwhile research experience. The students enjoyed learning cell culture techniques while contributing to active research projects. The institution's researchers were equally enthusiastic to instruct and serve as mentors. In this article, we clarify and illuminate the value of small-group laboratory apprenticeships to the institution and the students by presenting the results and experiences of seven middle and high school participants and their instructors.     

Probiotics and prebiotics in human health

Probiotic bacteria are found in the intestines of humans and other mammals where they provide health benefits to the host. They do so by (1) providing nutrients and cofactors, (2) successfully competing with pathogens, and (3) stimulating host immune responses by producing specific polysaccharides. These bacteria can also alleviate the symptoms of disease-related metabolic disorders. Prebiotics are substances, usually poorly metabolized polysaccharides and oligosaccharides, that cannot be ingested effectively by the animal. They stimulate the growth of intestinal probiotic bacteria, which can utilize these carbohydrates, thereby promoting health of the organism. Genetic engineering has proven useful for the design of probiotic bacteria that counteract the symptoms of genetic and age-related diseases. Can these bacteria be engineered, through human-promoted accelerative evolution, so that they stimulate their own growth and that of other probiotic bacteria so as to crowd pathogens out of the intestine?     

场效应晶体管生物传感器在生物医学检测中的应用研究进展*

场效应晶体管生物传感器因其灵敏度高、分析速度快、无标记、体积小、操作简单等特点而受到了很多关注,广泛应用于DNA、蛋白质、细胞、离子等生物识别物的检测。近年来,更有纳米材料和微电子技术在传感器设计中提高传感器的传感性能,场效应晶体管生物传感器朝着高灵敏、微型化、快速化以及多功能化的方向以令人惊叹的速度发展。研究场效应晶体管生物传感器工作原理,阐述近年来场效应晶体管生物传感器在生物医学检测领域中最新的研究进展与应用,探讨场效应晶体管生物传感器克服各种缺陷的应对策略,为该传感器在未来生物医学检测中的开发提供参考。     

A participatory learning approach to biochemistry using student authored and evaluated multiple-choice questions

A participatory learning approach, combined with both a traditional and a competitive assessment, was used to motivate students and promote a deep approach to learning biochemistry. Students were challenged to research, author, and explain their own multiple-choice questions (MCQs). They were also required to answer, evaluate, and discuss MCQs written by their peers. The technology used to support this activity was PeerWise--a freely available, innovative web-based system that supports students in the creation of an annotated question repository. In this case study, we describe students' contributions to, and perceptions of, the PeerWise system for a cohort of 107 second-year biomedical science students from three degree streams studying a core biochemistry subject. Our study suggests that the students are eager participants and produce a large repository of relevant, good quality MCQs. In addition, they rate the PeerWise system highly and use higher order thinking skills while taking an active role in their learning. We also discuss potential issues and future work using PeerWise for biomedical students.     

An Instruction on the In Vivo Shell-Less Chorioallantoic Membrane 3-Dimensional Tumor Spheroid Model

The traditional shell chicken chorioallantoic membrane (CAM) model has been used extensively in cancer research to study tumor growth and angiogenesis. Here we present a combined in vivo tumor spheroid and shell-less CAM three-dimensional model for use in quantitative and qualitative analysis. With this model, the angiogenic and tumorigenic environments can be generated locally without exogenous growth factors. This physiological model offers a stable, static and flat environment that features a large working area and wider field of view useful for imaging and biomedical engineering applications. The short experimental time frame allows for rapid data acquisition, screening and validation of biomedical devices. The method and application of this shell-less model are discussed in detail, providing a useful tool for biomedical engineering research.     

Teaching from classic papers: Hill's model of muscle contraction

A. V. Hill's 1938 paper "The heat of shortening and the dynamic constants of muscle" is an enduring classic, presenting detailed methods, meticulous experiments, and the model of muscle contraction that now bears Hill's name. Pairing a simulation based on Hill's model with a reading of his paper allows students to follow his thought process to discover key principles of muscle physiology and gain insight into how to develop quantitative models of physiological processes. In this article, the experience of the author using this approach in a graduate biomedical engineering course is outlined, along with suggestions for adapting this approach to other audiences.     

Biomolecular hydrogels formed and degraded via site-specific enzymatic reactions

We present polymeric hydrogel biomaterials that are biomimetic both in their synthesis and degradation. The design of oligopeptide building blocks with dual enzymatic responsiveness allows us to create polymer networks that are formed and functionalized via enzymatic reactions and are degradable via other enzymatic reactions, both occurring under physiological conditions. The activated transglutaminase enzyme factor XIIIa was utilized for site-specific coupling of prototypical cell adhesion ligands and for simultaneous cross-linking of hydrogel networks from factor XIIIa substrate-modified multiarm poly(ethylene glycol) macromers. Ligand incorporation is nearly quantitative and thus controllable, and does not alter the network's macroscopic properties over a concentration range that elicits specific cell adhesion. Living mammalian cells can be encapsulated in the gels without any noticeable decrease in viability. The degradation of gels can be engineered to occur, for example, via cell-secreted matrix metalloproteinases, thus rendering these gels interesting for biomedical applications such as drug delivery systems or smart implants for in situ tissue engineering.     

A BioBrick compatible strategy for genetic modification of plants

ABSTRACT: BACKGROUND: Plant biotechnology can be leveraged to produce food, fuel, medicine, and materials. Standardized methods advocated by the synthetic biology community can accelerate the plant design cycle, ultimately making plant engineering more widely accessible to bioengineers who can contribute diverse creative input to the design process. RESULTS: This paper presents work done largely by undergraduate students participating in the 2010 International Genetically Engineered Machines (iGEM) competition. Described here is a framework for engineering the model plant Arabidopsis thaliana with standardized, BioBrick compatible vectors and parts available through the Registry of Standard Biological Parts (www.partsregistry.org). This system was used to engineer a proof-of-concept plant that exogenously expresses the taste-inverting protein miraculin. CONCLUSIONS: Our work is intended to encourage future iGEM teams and other synthetic biologists to use plants as a genetic chassis. Our workflow simplifies the use of standardized parts in plant systems, allowing the construction and expression of heterologous genes in plants within the timeframe allotted for typical iGEM projects.     

Genetic engineering, welfare, and accountability

Comments on the implications of genetic engineering for animal welfare. Welfare problems associated with techniques used to achieve genetic changes; Detrimental effects of genetic modifications to welfare; Modification of farm animals for biomedical products. Implications of genetic engineering for animal welfare are changing rapidly and need to be reviewed regularly. They include the welfare problems associated with techniques used to achieve genetic changes, which are similar to problems of other experimental approaches; these should be considered carefully, especially where techniques are used on a routine basis. When it comes to the genetic modifications themselves, some are detrimental to welfare, some are neutral, and some are beneficial; these results include direct effects of the intended change, side effects, and indirect effects. Currently, the two main applications are modification of farm animals for biomedical products--which appears to be largely neutral for welfare--and modification of mice as models for human disease, which results in suffering, often severe suffering. Beneficial applications are rare and still experimental or theoretical. The situation is similar with regard to the use of recombinant hormones and viruses; use of recombinant vaccines has potential for improving welfare, but may raise other ethical problems. Although few, if any, of these concerns are specific to genetic engineering, various factors combine to suggest that particular safeguards are needed in this field. These include the facts that changes can be produced rapidly and repeatedly, and that one of the driving forces behind genetic engineering is commercial exploitation of technology. In general, ethical evaluation still is done on a case-by-case basis, using the limited criteria seen as directly relevant to each case, rather than on a broader framework. There also is little public accountability, whereby the public can have confidence that such evaluation is being carried out properly. Calls for advisory “watchdog ”committees to consider ethical questions on the use of animals are endorsed by this article. Furthermore, it is essential for public confidence in the safeguarding of animal welfare that the procedures of such committees should be well-publicized.     

Synthetic tissue biology: tissue engineering meets synthetic biology

We propose the term "synthetic tissue biology" to describe the use of engineered tissues to form biological systems with metazoan-like complexity. The increasing maturity of tissue engineering is beginning to render this goal attainable. As in other synthetic biology approaches, the perspective is bottom-up; here, the premise is that complex functional phenotypes (on par with those in whole metazoan organisms) can be effected by engineering biology at the tissue level. To be successful, current efforts to understand and engineer multicellular systems must continue, and new efforts to integrate different tissues into a coherent structure will need to emerge. The fruits of this research may include improved understanding of how tissue systems can be integrated, as well as useful biomedical technologies not traditionally considered in tissue engineering, such as autonomous devices, sensors, and manufacturing.     

Laboratory Design for Microbiological Safety

Of the large amount of funds spent each year in this country on construction and remodeling of biomedical research facilities, a significant portion is directed to laboratories handling infectious microorganisms. This paper is intended for the scientific administrators, architects, and engineers concerned with the design of new microbiological facilities. It develops and explains the concept of primary and secondary barriers for the containment of microorganisms. The basic objectives of a microbiological research laboratory, (i) protection of the experimenter and staff, (ii) protection of the surrounding community, and (iii) maintenance of experimental validity, are defined. In the design of a new infectious-disease research laboratory, early identification should be made of the five functional zones of the facility and their relation to each other. The following five zones and design criteria applicable to each are discussed: clean and transition, research area, animal holding and research area, laboratory support, engineering support. The magnitude of equipment and design criteria which are necessary to integrate these five zones into an efficient and safe facility are delineated.