Title: Concise Review on How Science and Technology Cooperate in Bioengineering
Author(s): Hamed Reza Seyyed Hosseinzadeh PhD 1*, Amir Reza Azadmehr PhD 2, Touraj Shafaghi MD 2
1 Amirkabir University of Technology, Tehran, Iran 2 Shahid Beheshti Medical University, Tehran, Iran
* Corresponding Author
Vol 2, Num 2, April 2015
Bioengineering is an almost new topic in science and technology as a multidisciplinary branch of science, that is, mathematics, physics, chemistry, materials science, mechanics, electronics, biology, medicine, engineering physics, engineering and many more cooperate in bioengineering. In this monograph, the importance and scientific background of bioengineering is introduced and then applied resultant technologies are followed. Biomaterials and biomechanics are introduced by instances and then their applications as scientific concepts and basis of bioengineering. Among lots of technological topics in bioengineering, tissue engineering, arthroplasty and sport medicine are highlighted. Finally, computational approaches and general used concepts of them are mentioned. This review is trying to show general trend in bioengineering instead of details.
Keyword:Bioengineering, Biomaterials, Biomechanics, Medicine, Healthcare, Simulation, Biotechnology, A.6, J.1, J.2, J.4
Literarily, bioengineering is the use of engineering principles for biological and medical issues. Although solving biological problems have historic background, bioengineering is relatively new and it is the multidisciplinary science and technology. Bioengineering has expanded to wide range of sciences and technologies from large scale technologies like orthopaedic, dental and hospital equipment to engineering at atomic, molecular and cellular levels.
Bioengineering has also applications in the environmental, plants  and energy issues as healthcare. This wide range of sciences and technologies means wide range of scientific/technological fields must cooperate tightly such as electrical, mechanical, chemical and materials engineers and scientific researchers in medicine, materials science, chemistry and biology.
In addition, bioengineering is covering the understanding of physical/chemical properties of cells, the natural design and function of tissues and organs, along with the main principles of molecules of life existence, composition, conformation and interplay within different physiological scenarios. These mentioned topics are used as the fundament for complex cellular and tissues/organs physiological functions such as function of heart, neuronal, skeletal muscle, and other cells and tissues like lungs, overall circulation, liver, gastrointestinal tract and kidneys. The emerging concepts of nanotechnology, drug delivery, advanced biomaterials, biomagnetism, and regenerative/cellular therapy changed and enhanced bioengineering techniques.
Figure 1 is summarizing overall features in bioengineering and these mentioned wide range of scientific and engineering topics are gathered in a concise graph.
Philosophy of scientific research and engineering design
Nowadays, we are thinking and examining our physical surround by three correlate methods for engineering design and scientific research. These are the so called modeling, simulation and experimental approaches (Figure 2a). All of these three approaches are successfully using in bioengineering. Modeling is referred to the scientific methods which is trying to construct algebra formula usually according to experimental data i.e. Newton's second law.
Simulation is about procedure to perform a virtual laboratory's experiences by computer and numerical methods. Due to the development of simulation techniques, it is necessary to revisit method of categorization of thinking to highlight the new features of each methods. Until now, academic scientists were emphasizing on experimental methods along with theoretical and simulation techniques. And they do not believe in the reliability of the results achieved just by the theory as those by experiment.
Answering to the following question would be very helpful to introduce and describe a new categorization on the mentioned subject, that is, modelling, simulation and experimental techniques:
“As any investigation runs to find something new, can one of these approaches works for this propose stand-alone (solely) without any relation to other two approaches?”
The easy answer is “No”. But there is some computational methods with accuracy higher than experimental results. So, in some cases the answer would be “Yes”. On what was mentioned, probably having different point of view would be helpful. It would be more practical to classify any justifications in applied sciences to three priori, post-priori and mixed scientific justification instead of modelling, simulation and experimental techniques.
Prior justification is for the cases if there is no argument based on experiment to achieve a rational cognition. Some recent advanced simulation methods such quantum mechanics computational calculation according to density functional theory could be placed in this category. In comparison, post-priori justification just refers to the cognition achieved through pure experimental techniques and approaches. The last one indicates to a mix of the two last mentioned approaches. Figure 2b is showing these three mentioned classifications. There is no relation between each of them in comparison what is shown in Figure 3a. Just select one of them to perform a research.
In general both computational and experimental methods are tightly working together for ultimate engineering design. Simulation methods enabled us to have deeper scientific insight. Nowadays, we are profited by advanced simulation methods to develop technologies better. Although any simulations are virtual perception of reality, advanced computational methods would have reliable accuracy close enough to realities. That is to say, curiosity and ambitious of mankind let to decoding of nature and even more to manipulating it accurately. Honestly, this noticeable successful experience is related to great efforts of expert minds over centuries.
Nowadays, without a doubt simulation methods will help theoretical and experimental scientists and scholars to decode the scientific puzzles better and wisely, that is, ultimate research success, hopefully. Leonardo da Vinci expresses this subject in a clever sentence, "He who loves practice without theory is like the sailor who boards ship without a rudder and compass and never knows where he may cast".
Biomaterials are used to serve in biological system. These kinds of materials (either natural or synthetic) are using to heal an imperfection or examining a bio issue. Wide range of length scale of these kinds of materials from atomic/molecular scale to marcoscale are well designed such as implantable medical devices, bioactive molecules, substrate to facilitate tissue regeneration.
Biomaterials must at least have non-immunogenicity, biocompatibility, less or controllable biodegradability and non-toxicity. Biomaterials are synthesized by different chemical and mechanical techniques. Then, the different shapes would be achieved such as thin films, nanofibers, nanoparticles and etc. Along with synthetic materials, natural ones are also very common in bioengineering such as bone, tooth, and nacre as nanocomposites of proteins and minerals with superior strength  and silk produced by silkworms or spiders. Architectures of silk are ideal as vehicles to transport and deliver bioactive molecules across boundaries.
Throughout history, biomaterials have significant impact on the treatment of disease and in general the improvement of health care. It seems that pure metals (mainly gold) and wood have early candidates for bio applications in dentistry. The use of gold in dentistry is very historic over 2000 years ago. Glass is also a good early example for synthetic eyes. During nineteenth century, advent of synthetic polymers changed our life and also had important effect on health care. At that time, the synthetic polymeric biomaterials became increasingly used in health care such as polymethylmethacrylate (PMMA) which was used in dentistry in the 1930s and then PMMA and advanced alloys were used in total hip replacements.
Advent of advanced biomaterials improved performance of bio advices such as those with low enough weight but high strength and almost similar elastic module to bone. One of these advanced biomaterials are Ti alloys, stainless steels and Co Alloys. Biomaterials are continuously improving for many bio applications like bearing stress, transporting electrical signals (designing materials that can sense biochemical signals in the body), having magnetic properties, having good flexibility and many more physical and mechanical properties, that is to say, numerous challenges remain in biomaterials development. Hence, Materials scientists and engineers are examining different kinds of materials like nanotube carbon, smart polymers, shape memory alloys, amorphous materials and fiber materials  to overcome mentioned issues. By the advent of these new materials in bioengineering, new topics like drug delivery and biomimetic were introduced as well. As an instance, drug delivery and biomimetic subjects are bioengineering fields to develop methods to overcome cancer disease.
As one of another high technology materials, smart polymers had explosive growth during three last decades and now their applications have been increasing significantly. As an instance for their application, smart polymers are known as bio stimuli or sensitive polymer used in the area of biotechnology, medicine and engineering. In general, researchers tries to mimic biopolymers such as proteins, polysaccharides and nucleic acids to improve functionalities of synthetic biopolymers. There is a rich and long history of gaining inspiration from nature for the design of practical materials and systems.[9-13]
Scientists put different names on synthetic biopolymers based on their physical, chemical and mechanical properties  namely “stimuli-responsive polymers” [14 and 15] or “smart polymers” [16 and 17] or “intelligent polymers”  or “environmental-sensitive” polymers.
As mentioned before, bioengineering scientists are developing new biomaterials to improve health care and heal a disease. But in rare cases, they are not trying to develop new biomaterials and just focusing on enhancing their understanding of physical and mechanical properties of natural biomaterials. One of these fields is dielectric properties of biological materials (dielectric spectroscopy). It is important because during past decade we were encountered to a dramatic development of wireless electrical systems which means a dramatic exposure of people to electromagnetic fields from wireless telecommunication devices and infrastructure. Knowledge of dielectric properties is consist of understanding the overall response of materials to external electric field and understanding charge distribution in materials. Biological materials have charges, that is to say, external electric field will cause them to drift and displace, thus inducing conduction and polarization currents.
In the same way, magnetic properties of biological material is also important for tracing and examining biological issues. Most biological materials have magnetic permeability close to free space which means no magnetic properties. However, it is not the case for all biological materials. In the case of natural biological materials, iron and its oxide role for their magnetic properties.
In addition, nanotechnology have opened a new windows to bioengineering. Nanotechnology in biomaterials is growing fast and wide range of solid and liquid materials were developed by this method. This technology could effectively develop materials to be compatible with proteins, inorganic, organic, virus and DNAs and to encapsulate and release mentioned materials. Nanoparticles developed by nanotechnology which are interacting with mentioned biomaterials would establish biological interactions at their interfaces. This is related to the biophysicochemical interaction science. Understanding these kinds of interactions are very important because of safe use of nano materials.
The nano–bio interface comprises three dynamically interacting components: (i) the nanoparticle surface, the characteristics of which are determined by its physicochemical composition; (ii) the solid–liquid interface and the changes that occur when the particle interacts with components in the surrounding medium; (iii) the solid–liquid interface's contact zone with biological substrates.
At nanoscale, most physical and mechanical responses need to revisit different from marcoscale. It is very important to understand the range of interactions forces and related consequences on neighbors. Several of kinds of forces and range of their interactions are as follows:
1. Hydrodynamic interaction (Range of effect: 100 to 10000 nm)
2. Electrodynamic interactions (Range of effect: 1 to 100 nm)
3. Electrostatics interactions (Range of effect: 1 to 100 nm)
4. Solvent interactions (Range of effect: 1 to 10 nm)
5. Steric interactions (Range of effect: 1 to 100 nm)
6. Polymer bridging interactions (Range of effect: 1 to 100 nm)
Biomechanics has been defined as the study of the movement of living things using the science of mechanics. Biomechanics is successfully using to study biofluid dynamics of cardiopulmonary bypass Surgery, biomechanics of artificial heart, biomaterials for an artificial pacemaker, biomaterials for carotid stenting, biomechanics of angioplasty: ballooning and stenting, biomechanics of artificial lung, biomechanics of artificial kidney, biomechanics of arthritis and human body pain, biomechanics of orthopaedic fixations, biomechanics of total knee replacement and biomechanics of dental prostheses.
Although this field is usable for wide range of medicine, very common instance of biomechanics application in clinical issues is gait analysis during walking/stair climbing and musculo-skeletal models.[25 and 26] A fundamental understanding of the biomechanics of normal walking and running is important before addressing walking and running disorders. Discussion on different aspects of the biomechanics of gait such as the gait cycle events, joint kinematics (angular charges) and joint kinetics (moments and powers) and compares these aspects as they relate to walking and running.
Hip and knee replacements make great challenges to orthopedic surgeons and for this subject, every patient requires thorough pre-operative planning. In this case, biomechanics is very important and playing important role for total hip and knee arthroplasty. Walking velocity is reduced in total hip arthroplasty patients. Stride length and hip range of motion in the sagittal plane are also reduced in total hip arthroplasty patients. Future developments in implant design and surgical approach should, therefore, focus on improving patient outcomes in relation to walking velocity, hip range of motion in the sagittal plane, stride length, and peak hip abductor moments which significantly related to biomechanical studies.
In addition, implant price is an important component of the overall cost of total joint arthroplasty. With the aim of decreasing the cost of implants for total hip arthroplasty and total knee arthroplasty, a number of different options have been tried, including instituting awareness programs among surgeons, implant matching, the use of older designs, recycling implants, competitive bidding, and volume discounting which are tightly to the knowledge of biomechanics of implants.[31-37]
In mechanical engineering and mechanics, mathematical structure are well developed and this field of science has standard numerical methods and constitutive equations to calculate any mechanical variables. This advanced mathematical and computational mechanical approaches are successfully using in bioengineering. One of the famous numerical method is Finite element.
The finite element method (FEM) is an advanced computer simulation technique for evaluating structural stress. In 1972, this method was developed in engineering mechanics and introduced to orthopedic biomechanics. First, it was used for evaluation of human bones stresses. Nowadays, this method is used for boneprosthesis structures, fracture fixation devices and various types of tissues and understanding physical mechanisms i.e. finite element analysis of friction for hip endoprosthesis systems , finite element simulation of knee  and finite element simulation to understand stress distribution in fractured femoral neck bone and dynamic hip screw device.
Along these numerical methods, mathematical models are also developed in bioengineering like a mathematical contact stress distribution model to analyze the implant and the surgical factors  and gait mathematical dynamical model during walking, stair climbing and pedaling.
Biomechanics is not restricted to the solid materials. Fluid mechanics is also very important in bioengineering. As instance, studies have shown  that the form and/or function of the mitochondrial network are affected when endothelial cells are exposed to shear stress in the absence or presence of additional physico-chemical stimuli. Understanding how the local hemodynamics affects mitochondrial physiology and the cell redox state may lead to development of novel therapeutic strategies for prevention or treatment of the endothelial dysfunction and, hence, of cardiovascular disease.
Fluids are Newtonian or non-Newtonian and lamellar or turbulent. Biomechanics of non-Newtonian fluids are important in studying of biological fluids like blood, synovial liquid, saliva, and cell constituents. Fluid mechanical studies became more important by the advent of new high technological facilities in medicine like laser and ultrasound facilities for surgery.
Whenever laser pulses are used to ablate or disrupt tissue in a liquid environment, cavitation bubbles are produced which interact with the tissue. The interaction between cavitation bubbles and tissue may cause collateral damage to sensitive tissue structures in the vicinity of the laser focus, and it may also contribute in several ways to ablation and cutting. These situations are encountered in laser angioplasty and transmyocardial laser revascularization. This last case is showing the importance of understanding fluid biomechanical description.
Cell and tissue research is a very active field in bioengineering.[45-47] Tissue engineering (TE) is an approach that attempts to combine engineering principles with the biological sciences to produce viable structures for replacement of diseased or deficient native structures. Tissue engineering is an interdisciplinary field of study that addresses this challenge by applying the principles of engineering to biology and medicine toward the development of biological substitutes that restore, maintain, and improve normal function.
A popular method in tissue engineering is to utilize a bioabsorbable scaffolding material to ultimately produce a functional living tissue that can be implanted into the body . Tissue engineered heart valve is another instance. Surgical replacement of diseased heart valves by mechanical and tissue valve substitutes is now commonplace and enhances survival and quality of life for many patients.
Joint replacement is still one of the major successes of modern medical treatment, transforming the lives of the increasing number of older individuals in the population as well as now offering a realistic return to normality in younger patients with problem joints.
Tribology plays an important role in the functioning of artificial joints. Hip joints are subjected to a large dynamic load, up to a few times bodyweight during normal walking, and yet this is often accompanied by a large range of motions. Friction played an important role in the design of the low possible friction implants. Wear and corrosion are important, not only from the point of view of the integrity of the prosthetic component, but also from that of wear debris generation which can cause adverse biological reactions. Lubrication can be the most effective means to reduce both friction and wear.
However, the following five wear mechanisms are usually used to describe the fundamental wear process :
1. Abrasive: the displacement of materials by hard particles.
2. Adhesive: the transference of material from one surface to another during relative motion by the process of solid-phase welding.
3. Fatigue: the removal of materials as a result of cyclic stress variations.
4. Erosive: the loss of material from a solid surface due to relative motion in contact with a fluid which contains solid particles. This is often subdivided into impingement erosion and abrasive erosion. If no solid particles are present, erosion can still take place such as rain erosion and cavitation.
5. Corrosive: a process in which chemical or electrochemical reactions with the environment dominates, such as oxidative wear.
Intensive research efforts have been placed on the development of biomaterials with improved cell and tissue compatibility. Most of these works have focused on modifying material properties to reduce the accumulation and activation of inflammatory cells, especially macrophages.
In addition, corrosion is very important and it has two folds effect on overall performance of implant technology. Degradation and corrosion would deteriorate implant (crevice/pitting/fretting corrosion, corrosion fatigue and stress corrosion cracking) and also release produces have detrimental effects on host (wear and corrosion produces would lead to periprosthetic bone loss). Corrosion of orthopaedic implants remains clinical concern.
Various causes for failure of implants are wear/corrosion, fibrous encapsulation, inflammation, low fracture toughness/low fatigue strength and mismatch in module of elasticity of bone and implant. These are main reason for revision of surgery.[52 and 53]
Bioelectronics technologies have strong potential to improve human health and to enhance the understanding of living systems. Electronic systems, such as circuits and sensors, and optoelectronic systems, such as light-emitting diodes and photodetectors, that combine state-of-the-art operational characteristics with soft, elastic mechanical properties even under large-strain deformations. Such devices can be bent, twisted, folded, stretched and conformally wrapped onto arbitrarily curved objects, without significant change in performance.
One of active research field in bioelectronics is biomolecular Electronics. In the literature, when we say biomolecular electronics we imply the use of biomolecules or their complexes for application as independent functional devices capable of interfacing with modern electronic devices. Typical examples would be biosensors, widely used in medicine, or the lesser known photoconverters.
Molecular electronics as a term was established in the early 1980s. Naturally, long before that, many scientific groups had been studying electronic processes at the molecular level. However, it was not until the emergence of nanotechnology and the construction of molecular and atomic resolution devices, that molecular electronics was recognized as a new branch of science. The main modern-day strategies of molecular electronics can already be singled out:
* Employment of chemosynthesis methods in biology for the synthesis of live system analogs.
* Imitation of biological structures and/or their functions, using various scientific methods. This direction is sometimes called "the synthetic design for biomimetics".
* Application of natural protein complexes as ready-to-use technological elements.
* The use of photoelectric effects in phototransforming and photosynthesizing proteins for the needs of molecular optoelectronics.
* Solution of the so-called "problem of molecular interfacing between biomaterials and the outside world," in other words, elimination of the incompatibility between the biological part of the element and traditional microelectronic elements.
* Genetic engineering of new proteins with pre-determined properties and without natural analogs.
* Exploration of the molecular recognition mechanism (the "key-lock" principle), which is extremely important for the progress of studies on self-assembling microelements, or even larger systems.
Bioelectronics is also a field in computer science. A significant advantage of natural "computers" (biomolecular computers) over the computers of today is that the size of the elements responsible for information processing, storage, and transmission, and the expenditure of energy per unit of information, is much smaller in live organisms. Another distinction is that biomolecular computation in a natural system has neither serial, nor parallel circuitry. Finally, and perhaps most importantly, the brain and systems connected to the brain, are capable of pattern-recognition, self-adaptation to environmental fluxes, process controlling, filtration of inform action and self-assembly.
Orthopedic sports medicine has a broad area of interest from the prevention of sports injuries, diagnosis, treatment, and rehabilitation of athletes, children, females, as well as older people. To improve the orthopedic sports medicine, biomedical engineering with a special emphasis in the musculoskeletal system offers isolating the problem and developing a set of hypotheses tested with experiments, modeling, and theoretical methods.[57 and 58]
Sport medicine is covering all different kinds of sports and some related topics for each sport in medicine and bioengineering are summarized as follows :
a. Aerodynamics of the Golf Ball
b. Engineering Methodology in Golf Studies
c. Physics and Mechanics of the Golf Swing
d. Eye and Head Movements during the Golf Putting Stroke
a. Tennis Ball Aerodynamics and Dynamics
b. Shoe-Surface Interaction in Tennis
c. Biomechanics of Tennis Strokes
d. Optimizing Ball and Racket Interaction
a. Biomechanics of Pitching
b. The Rising Fastball and Other Perceptual Illusions of Batters
IV. Football and soccer
a. Aerodynamics of the Forward Pass
b. Biomechanics of Tackling
c. Biomechanics and Aerodynamics in Soccer
a. Aerodynamics and Biomechanics of the Free Throw
b. Make Every Free Throw
VI. Performance and rehabilitation
a. Vision Training and Sports
b. Application of Biomedical Principles to the Maturation of Skills in Children
c. Medical Advances in the Treatment of Sports Injuries
Computational Approach and Software
Nowadays, simulation methods are well developed by advanced physical and mathematical methods. Main physical sciences are quantum mechanics, classical physics, relativistic and non-relativistic theories. According to the physical constraint on size and velocity of under consideration system, computational techniques are categorized and limited to a special computational technique. Figure 3 is summarized the mentioned categorization.
Any computational methods and simulation techniques in bioengineering has following mathematical and physical backgrounds:
1. Matrices and Tensors, partial differential equation, numerical method.
2. Continuum and discrete Mechanics
3. Heat Transfer, Diffusion, Fluid Mechanics, and Fluid Flow through Porous Deformable Media
4. Numerical methods:
i. Finite Element Analysis
ii. Dynamic Finite Element Analysis
iii. Nonlinear Finite Element Analysis
iv. Discrete Particle Methods
v. Finite difference analysis
vi. Meshless analysis
vii. Finite volume analysis
Computational methods and mentioned techniques were successfully applied to following topics in bioengineering :
i. Bone Modeling
ii. Soft tissue
iii. Skeletal muscle
iv. Blood flow and blood vessel
v. Modeling Mass Transport and Thrombosis in Arteries
vi. Cartilage Mechanics
vii. Cell Mechanics
viii. Cancer Nanotechnology
To perform a simulation for bioengineering issues, there is no need to learn all of above topics which are not very simple and several commercial software and freeware are available for this propose.
ANSYS (www.ansys.com), OBACUS (www.3ds.com/products-services/simulia/products/abaqus/), COMSOL (www.comsol.com) are well developed commercial software for biomechanical marcoscale simulation. On the other hand, for atomistic simulation of biomolecules, VASP (www.vasp.at) and abinit (www.abinit.org) are the most famous packages. QUMEC (www.qumec.org) packages is provided for atomistic simulation. Figure 4 shows interface of QUMEC. mQUMEC (www.qumec.org) software is a general software for performing general simulation to design orthopeadic implants. Figure 5 shows interface of mQUMEC.
Bioengineering is a new and multidisciplinary topic in science and technology and many high technological facilities are being used in this fields. Bioengineering has applications in the healthcare, environmental, plants and energy issues. Biomaterials and biomechanics are the two main scientific basic topics in bioengineering.
All advanced computational methods are being successfully used in this field as well. In addition, bioengineering is covering the understanding of physical/chemical properties of cells, the natural design of tissues and organs (like of heart, neuronal, skeletal muscle, lungs, liver and kidneys), understanding main principles of molecules of life existence, composition, conformation and interplay within different physiological scenarios.
Hamed Reza Seyyed Hosseinzadeh PhD Computational materials science and engineering scientist/researcher, Department of Mining and Metallurgical Engineering, Amirkabir University of Technology, Tehran, Iran Corresponding author firstname.lastname@example.org
Amir Reza Azadmehr PhD Assistant Professor, Department of Mining and Metallurgical Engineering, Amirkabir University of Technology, Tehran, Iran email@example.com
Touraj Shafaghi MD Assistant Professor, Orthopaedic Surgeon, Shahid Beheshti Medical University, Tehran, Iran firstname.lastname@example.org
Acknowledgements: None declared.
Financial disclosure: None declared.
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