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.     

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。     

Biomimicry in biomedical research

Biomimicry (literally defined as the imitation of life or nature) has sparked a variety of human innovations and inspired countless cutting-edge designs. From spider silk-made artificial skin to lotus leaf-inspired self-cleaning materials, biomimicry endeavors to solve human problems. Biomimetic approaches have contributed significantly to advances biomedical research during recent years. Using polyacrylamide gels to mimic the elastic modulus of different biological tissues, Disher’s lab has directed meschymal stem cell differentiation into specific lineages.¹ They have shown that soft substrates mimicking the elastic modulus of brain tissues (0.1~1 kPa) were neurogenic, substrates of intermediate elastic modulus mimicking muscle (8 ~17 kPa) were myogenic, and substrates with bone-like elastic modulus (25~40 kPa) were osteogenic. This work represents a novel way to regulate the fate of stem cells and exerts profound influence on stem cell research. Biomimcry also drives improvements in tissue engineering. Novel scaffolds have been designed to capture extracellular matrix-like structures, binding of ligands, sustained release of cytokines, and mechanical properties intrinsic to specific tissues for tissue engineering applications.^2,3 For example, tissue engineering skin grafts have been designed to mimic the cell composition and layered structure of native skin.⁴ Similarly, in the field of regenerative medicine, researchers aim to create biomimetic scaffolds to mimic the properties of a native stem cell environment (niche) to dynamically interact with the entrapped stem cells and direct their response.⁵     

Ethics and biomedical research

Ethics in biomedical research took off from the 1947 Nuremberg Code to its own right in the wake of the Declaration of Helsinki in 1964. Since then, (inter)national regulations and guidelines providing a framework for clinical studies and protection for study participants have been drafted and implemented, while ethics committees and drug evaluation agencies have sprung up throughout the world. These two developments were crucial in bringing about the protection of rights and safety of the participants and harmonization of the conduct of biomedical research. Ethics committees and drug evaluation agencies deliver ethical and scientific assessments on the quality and safety of the projects submitted to them and issue respectively approvals and authorizations to carry out clinical trials, while ensuring that they comply with regulatory requirements, ethical principles, and scientific guidelines. The advent of biomedical ethics, together with the responsible commitment of clinical investigators and of the pharmaceutical industry, has guaranteed respect for the patient, for whom and with whom research is conducted. Just as importantly, it has also ensured that patients reap the benefit of what is the primary objective of biomedical research: greater life expectancy, well-being, and quality of life.     

^19FNMR在生物医学研究中的应用

核磁共振（ＮＭＲ）是一种无创伤的物理测试方法,它可以直接用于体内和体外的生物样品测定,提供分子水平的信息。正常体内含氟成分很少,测定进无本底信号干扰,因此在体内研究中引进氟代指示剂进行＾１９ＦＮＭＲ研究是目前普遍采用的方法。＾１９ＦＮＭＲ可可以用来测定药物在体内代谢过程、胸内游离的离子如Ｃａ＾２＋和Ｍｇ＾２＋、胞内ｐＨ、氧浓度或氧压力（ｐＯ２）、膜电位、组织温度、血液容积和细胞容积等多项生理生化指     

Ethical review in biomedical research

Through the difficulties encountered during the previous centuries in order for an animal to be recognized as a sensitive being, we saw the evolution of society's attitudes change from antiquity to our present day. Over the past twenty years animal testing has first evolved within a progressive regulatory framework reinforced by an ethical thinking which has, since 1990, led to the establishment of the ethics committees. The dialogue between these committees and researchers has led to the recovery of principles previously ignored such as the 3Rs (Replace, Reduce, Refine). This in turn has led to the application of improving experimental conditions, the progressive decrease in the number of animals used through a wise use and the replacement of animals by in vitro techniques in the very preliminary stages of research. Progress remains to be done, but the evolution of European regulations being amended, the formalization in France of ethics committees and the establishment of the National Ethics Committee should further contribute to the improvement of animal welfare in experimental research.     

The muskrat in biomedical research

Muskrats are aquatic rodents of moderate size which are plentiful throughout North America, but are not used commonly in the laboratory. Recently, we tested the feasibility of muskrats as experimental models and have found them to be acquired and cared for easily in conventional laboratory animal facilities. Some of their natural characteristics and diseases are described. The husbandry techniques that we used are presented and form a base for the preparation of future guidelines for the maintenance and use of feral animals in research. The results of some initial experiments testing the muskrat's utility for investigations of cardiorespiratory control mechanisms also are presented. Our data show that even anesthetized muskrats possess brisk and dramatic cardiovascular and respiratory reflexes. Our findings that their brains possess the cytoarchitectural and myeloarchitectural features comparable to other mammals, combined with their relative uniformity in size, has allowed us to locate specific neuronal loci stereotaxically. We suggest that the muskrat be considered as an experimental animal model for studies of the neural control of cardiorespiratory systems.     

Human-animal chimeras in biomedical research

Chimeras are individuals with tissues derived from more than one zygote. Interspecific chimeras have tissues derived from different species. The biological consequences of human-animal chimeras have become an issue of ethical debate. Ironically, human-animal chimeras with human blood, neurons, germ cells, and other tissues have been generated for decades. This has facilitated human biological studies and therapeutic strategies for disease.     

Application of MRI and biomedical engineering in speech production study

Speech production has always been a subject of interest both at the morphological and acoustic levels. This knowledge is useful for a better understanding of all the involved mechanisms and for the construction of articulatory models. Magnetic resonance imaging (MRI) is a powerful technique that allows the study of the whole vocal tract, with good soft tissue contrast and resolution, and permits the calculation of area functions towards a better understanding of this mechanism. Thus, our aim is to demonstrate the value and application of MRI in speech production study and its relationship with engineering, namely with biomedical engineering. After vocal tract contours extraction, data were processed for 3D reconstruction culminating in model construction of some of the sounds of European Portuguese. MRI provides useful morphological data about the position and shape of the different speech articulators, and the biomedical engineering computational tools for its analysis.