Biomimicry 101: Turbulence and Chaos Theory

eagles-wingsFigure: The upward curvature (called winglets) found on the tips of wings in certain bird species, such as the bald eagle, increases aerodynamic efficiency by helping reduce drag.

When you ponder biomimicry, think design, intelligent design, and creation, but please don’t think evolution. And when considering biomimetic applications, let your imagination know no bounds.

Turbulence is the name for the small eddies that break off of larger ones; it is dissipative; it is unstable and dynamical. In fact, the study of turbulence is at the core of chaos and non-linear, dynamical systems – a subfield within mathematics with special appeal to mathematical physicists. For instance, the vortices (i.e., turbulence) that whirl off the wings of Boeing or Airbus passenger jets will differ greatly from those off the most sophisticated jet fighters, such as the F-18 Super Hornet. No matter what, each plane has its own “fingerprint” when it comes to air flow dynamics across their wings. And this characteristic signature is even more complex and dynamical for sweep-wing planes, such as the now retired but amazing F-14 Tomcat.

Of interest, just yesterday, July 19th, 2019, Airbus released a conceptual model of a large passenger prop plane with splayed wingtips and a fanned tail. This “hybrid” design attempts to reduce as much of the turbulent air flow as possible by mimicking the wings of soaring eagles.

Remark: Current models of many mid-sized to large passenger jets and cargo planes already have winglets to minimize the swirling eddies at the tips of their wings.

What is more, to help promote mathematical thinking and biomimicry, Andrew McIntosh, professor of thermodynamics and combustion theory, at the University of Leeds has held paper airplane design contests. These contests offer students a hands-on approach to help creativity form in the minds of future engineers.

Something completely different but related: aerospace and aviation

Today marks the 50th anniversary of the Apollo 11 moon landing!

On July 20, 1969, Neil Armstrong and Buzz Aldrin navigated the lunar module they piloted, named the Eagle, down onto the surface of the moon. Within moments of their landing, Armstrong radioed NASA Mission Control in Houston, Texas, his now infamous message, “Houston, Tranquility Base here. The Eagle has landed.” Soon afterwards, Armstrong made a more profound statement when he became the first person to set foot on the moon, saying, “That’s one small step for man, one giant leap for mankind.”

Three years later, on July 20, 1972, the Armstrong Air and Space Museum in Wapakoneta, Ohio, — the birthplace of Armstrong — opened its doors.

We invite you to return to our 2018 visit to the museum (click here).

Can you imagine a career in mathematics that might even help mimic nature – God’s great creation?

Starting out now on your very own discovery of the intricacies of God’s creation through scientific study might very well help you in discerning what path you should take in the future. Christian scholarship that extends into professional roles — such as mathematicians, engineers, and physicists who work in chaos and non-linear dynamics or aerospace and aviation to biologists and zoologists who study ornithology — is sincerely needed in education and society.

Biomimicry 101: Other Biomimetic Medical Advances: Progress and Steps to Diabetic Solutions and Spinal Cord Regeneration

other-biomimetic-solutionsFigure: The islets of Langerhans (left panel), and a spinal cord neuron (right panel).

When you ponder biomimicry, think design, intelligent design, and creation, but please don’t think evolution. And when considering biomimetic applications, let your imagination know no bounds.

Given our claim that the heart’s design is inherently unique and complex, an argument concerning the uniqueness of the pancreas can likewise be made, and is equally valid. Both arguments stem from knowledge that we are a special creation of God’s creative work. What is more, many features of the pancreatic organ-system are conducive to biomedical mimicry, which is important for people whose pancreas is limited functionally. Therefore, as we continue this series, we want to spotlight the work by Fournier, Goldblatt, Horner, and Sarver (1995) on patenting a bioartificial pancreas for combating diabetes (with the patent first filed in 1993). As we shed light on their process, our hope is students will not only gain valuable insight into ways to approach innovative ideas in health care, but also through God’s leading develop enthusiasm about career choices in mathematics and medicine, including more heavily-weighted bioengineering disciplines, such as microbiology and biochemistry. In our view, a general familiarity with the steps taken to patent a bioartificial pancreas can be used to engineer other devices that also fight diabetes or other diseases or disorders, such as cancer or spinal cord injury, via biomimetic solutions. Ultimately, the key to any medical endeavor is to get ideas into the clinical trial stage.

Biomimetic diabetic solutions

According to an educational web-based forum about the pancreas, as sponsored by the National Institutes of Health (2018), this organ has two important functions:

  • Production of enzymes (collectively, lipases, proteases, and amylases) that break down food in the digestive tract
  • Production the hormones insulin and glucagon to regulate blood sugar

— Mathematical Model —

Having a mathematical model in your tool belt is always a good thing. There are occasions when both invention and mathematics resolve themselves simultaneously. Sometimes the invention logically comes first, and the underpinning mathematics comes later. However, mathematical models can be generated prior to pressing forward with an invention.

In the 1990 article “Mathematical Modeling of a Novel Bioartificial Pancreas Design for the Control of Type I Diabetes,” Sarver and Fornier apply numerical analysis to their work on a bioartificial pancreas. We will leave it to you to decide the way in which Fournier, Goldblatt, Horner, and Sarver applied the mathematics to solve their case for a bioartificial pancreas patent (before, simultaneously, or after).

What is Numerical Analysis?

Numerical analysis is the iterative application of mathematics. Prior to the development of computers, numerical methods were necessary for solving engineering-based problems. With the aid of computers, numerical methods (i.e., iterative processes) have become a much more powerful tool because computers can perform the iterations much faster than we can calculate them. Numerical analysis takes advantage of algorithms to attain an approximation; it may be best defined as a branch of mathematics that places emphasis on the numbers rather than the symbols.

Numerical methods can be a beneficial component to any college undergraduate study in the STEM (science, technology, engineering and mathematics) majors. What is more, a numerical methods course is oftentimes recommended for junior-level (i.e., third-year) college STEM undergraduates. Prerequisites include high school algebra, differential calculus, integral, calculus, and ordinary differential equations.

Please click here to learn more about numerical methods.

The Bioartificial Pancreas

The first page of U.S. Patent No. 5,387, 237 (1995), shows Fournier, Goldblatt, Horner, and Sarver’s patent summary (i.e., the abstract) for their bioartifical pancreas, as follows:

An implantable bioartificial pancreas device having an islet chamber containing glucose responsive and insulin-secreting islets of Langerhans or similar hormone secreting cells, the islet chamber having baffle means inside thereof to assist in even distribution of the islets in the chamber, one or more vascularizing chambers open to surrounding tissue, a semi-permeable membrane between the islet and vascularizing chambers that allows passage of small molecules including insulin, oxygen and glucose and does not allow passage of agents of the immune system such as white cells and antibodies, the vascularizing chambers containing a growth factor soaked fibrous or foam matrix having a porosity of about 40 to 95%, the matrix providing small capillary growth and preventing the blood from clotting in the lower chamber.

Efforts toward spinal cord regeneration

To help us navigate toward a delivery method for spinal cord tissue regeneration, we consider a bioengineering survey and literature review by Wininger, Deshpande, and Bester (2012), who examined suitable ideas for delivery methods for the regeneration of the lumbar disc based on vascular supply/penetration, as follows:

Kloth et al issued a report on patient selection criteria for IDET in 2008.17 Notably, the criteria outlined in the report supports our decision to refrain from pursuing IDET in this case. Furthermore, similar to discography, percutaneous intradiscal radiofrequency thermocoagulation, and intradiscal biacuplasty, IDET requires needle placement into the disc.

When considering needle placement into a disc, it is important to consider the long-term effects of disc puncture. On this point, the biological effects of disc puncture continue to be debated in the literature. A recently published 10-year follow-up study on provocative lumbar discography by Carragee et al claims accelerated disc degeneration was associated with disc penetration injuries during discography.18

Perhaps more interesting is consideration of the knowledge gleaned from investigations on central disc vascular supply relative to disc puncture. A prospective study conducted by Deshpande et al on lumbar discography first confirmed real-time intravascular uptake of iodinated contrast media in 14.3% of the studied patient population.19 Further, although such episodes of uptake continue to be observed,2 it has long been observed in the radiological community that the intervertebral disc might enhance on MR images if examination start is delayed over a 30-minute window after gadolinium administration.20 Furthermore, serial MR images clearly demonstrate the phenomenon known as diffusion march (ie, the diffusion of gadolinium across the vertebral endplates and into the disc) with no intradiscal enhancement noted at 24 to 48 hours after contrast administration.21 Thus, for interventional pain physicians, broader implications of these vascular supply studies may help remedy delivery challenges related to bioengineering designs to regenerate the intervertebral disc, such as tissue scaffolds, mesenchymal stem cell therapy, or biomolecules to act as biochemical mediators within the disc.22-31

Finally, we highlight a forward-thinking concept of “direct” electrical stimulation of the intervertebral disc to induce analgesia. This novel technique places a percutaneous SCS lead inside or just outside the confines of the disc, thus sparing as much disc tissue as possible.32 However, the idea of electrically stimulating the disc in this manner has yet to be proven surgically feasible or provide clinically acceptable pain control. Thus, members of the interventional pain medicine community interested in neuroaugmentive techniques are involved in a truly transformative era of research.11,12 Electrical stimulation of the intervertebral disc could provide benefit for the disc’s cells and tissue, or provide beneficial synergies. For example, electromagnetic field stimulation has been shown in vitro to promote human intervertebral disc DNA synthesis. In addition, electrical stimulation applications could be used to promote cellular proliferation as an amplification process in autogenous disc cell therapy to regenerate disc tissue.33 (p. 434)

With this survey in mind, however, the hope for regeneration of spinal cord tissue hinges on demonstrable safety in crossing the blood and central nervous system barrier (better known as the “blood-brain barrier”).

Can you imagine a career advancing medicine through insight into solutions that might mimic nature? Nature and the universe in its entirety is God’s great creation; as His special creation, we can certainly look upon our Creator as Physician!

Christian scholarship extending into professional roles is sincerely needed in education and culture. Chemical engineering, bioengineering, and medicine can be promising careers for those who like to study physiology, microbiology, biochemistry, and mathematics.

References

Fournier, R.L., Goldblatt, P.J., Horner, J.M., & Sarver, J.G. (1995). Bioartificial pancreas. U.S. Patent No. 5,387, 237. Washington, D.C.: U.S. Patent and Trademark Office. [View patent]

National Institutes of Health. (2018). Informed health online. How does the pancreas work? Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK279306/.

Sarver, J.G., & Fornier, R.L. (1990). Mathematical modeling of a novel bioartificial pancreas design for the control of type I diabetes. Mathematical and Computer Modelling, 14, 551-556. [View in article]

Wininger, K.L., Deshpande, K.K., & Bester, M.L. (2012). Persistent pain following lumbar disc replacement. Radiologic Technology, 83(5), 430-436. [View abstract] [View in PubMed]

Previous articles in this series:

Biosensors will be featured in the next installment of our biomimicry series!

Biomimicry 101: Cardiovascular Medicine: Part 2: Cardiac Tissue Engineering and Other Novel Biomimetic Research

coronary-angioFigure 1: Coronary angiogram depicting adequate perfusion of the myocardium via the left coronary vasculature: the left main trunk branching out to form the left anterior descending and circumflex arteries. Among the areas of the heart that these arteries perfuse, the left-sided vasculature ultimately feeds – supplies oxygen to – the left ventricle.

Cardiovascular disease accounts for more deaths per year than all forms of cancer combined.

– American Heart Association, 2016

Given the complex yet interrelated structure and physiological design of the heart, we now center our discussion on biomimicry and bioengineering in cardiovascular medicine. First, we discuss multipotent and pluripotent stem cell therapy with respect to tissue engineering and regenerative science in cardiovascular research. Second, we expand briefly on the concept of cell plasticity related to cardiovascular medicine. Third, we point out the evolving role of protein therapy in cardiology, such as efforts to treat heart attack (i.e., myocardial infarction) by reprogramming/regenerating heart muscle cells (i.e., the cardiac myocytes). Fourth, we highlight a novel approaches to reperfusion therapy. Finally, we explore a variety of other biomimetic applications that have promising potential to impact cardiac and endovascular patient care.

When you ponder biomimicry, think design, intelligent design, and creation, but please don’t think evolution. And when considering biomimetic applications, let your imagination know no bounds.

Multipotent and pluripotent (induced pluripotency) stem cell therapy for tissue engineering and regenerative science in cardiovascular research

Cardiovascular disease (both coronary and cerebrovascular disease) accounts for more deaths per year than all forms of cancer combined (American Heart Association, 2016). Given that cardiomyocytes have a rate of turnover of 1% in youth to 0.5% in old age (Tchao et al., 2013), the heart is one of the least regenerative organs in the body. Currently, efforts remain ongoing for repopulating damaged/injured cardiac muscle tissue (the myocardium) via stem cell therapy (Naumova & Yarnykh, 2014). Moreover, it is often the case that tissue injury or damage results from ischemic events, such as heart attacks (also known as a myocardial infarctions). In fact, therapeutic goals and clinical outcomes driving much of the work behind regenerative cardiovascular research have to do with preventing the post-infarct heart from sliding into a low-functioning state of utility by regenerating the cardiomyocytes. One such approach gaining favor in recent years is the use of multipotent and pluripotent stem cells, as opposed to totipotent stem cells. Whereas totipotent stem cells are taken from embryonic tissue, multipotent and pluripotent stem cells (as well as induced pluripotency stem cells) are harvested from adult tissue and are less problematic to the recipient heart (Baldassarre, Cimetta, Bollini, Gaggi, & Ghinassi, 2018; Hirt, Hansen, & Eschenhagen, 2014; Purdom, 2007). However, because of the ability to perpetually divide, pluripotency is more advantageous with respect to the heart. Below we survey progress made in the use of pluripotent-derived cardiomyocytes. In addition, we review advances made in cardiac DTI that allow this non-invasive imaging technique to gain favor as the leading platform for the evaluation of infarct healing (via stem cell therapy) after ischemic injury in patients post-heart attack.

— Multipotent and (induced) Pluripotent Stem Cell Therapy —

With each ischemic insult that fully manifests as a heart attack, the myocardium will lose approximately one billion cardiomyocytes (i.e., the cardiac muscle cells) (Naumova & Yarnykh, 2014). What is more, such robust, immediate loss of myocardial tissue dramatically affects cardiac hemodynamics (including reduced cardiac output). Furthermore, after the initial ischemic injury, as well as the initial change in hemodynamics, a functional decline occurs over time (such as further reduced cardiac output) that can limit the physical capacity of a patient due to left ventricular remodeling. Such anatomical and physiological decline is termed heart failure. However, therapeutic strategies based on “patching” the cardiac muscle damage at or near the time of event onset (given that the patient is hemodynamically stable) by means of stem cell therapy can curb the detrimental progression of heart attack-induced heart failure, and this is especially the case with induced pluripotent-derived cardiomyocytes (Baldassarre, Cimetta, Bollini, Gaggi, & Ghinassi, 2018).

What do we mean when we say totipotent, multipotent, pluripotent, or induced pluripotent?

Totipotent – The state of a cell that is capable of giving rise to all types of differentiated cells found in an organism, as well as the supporting extra-embryonic structures of the placenta. A single totipotent cell could, by division in utero, reproduce the whole organism.

Multipotent – Having the ability to develop into more than one cell type of the body.

Pluripotent – The state of a single cell that is capable of differentiating into all tissues of an organism, but not alone capable of sustaining full organismal development. In other words, pluripotent stem cells can give rise to any type of cell in the body except those needed to support and develop a fetus in the womb.

Induced pluripotent stem cell – A type of pluripotent stem cell, similar to an embryonic stem cell, formed by the introduction of certain embryonic genes into a somatic cell, in which somatic cells are differentiated, mature cells. What is more, somatic cells are commonly referred to as “adult” cells.

Why pluripotent is important!

According to the National Institutes of Health website (n.d.):

In late 2007, scientists identified conditions that would allow some specialized adult human cells to be reprogrammed genetically to assume a stem cell-like state. These stem cells are called induced pluripotent stem cells (iPSCs). IPSCs are adult cells that have been genetically reprogrammed to an embryonic stem cell–like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. Although these cells meet the defining criteria for pluripotent stem cells, it is not known if iPSCs and embryonic stem cells differ in clinically significant ways. Mouse iPSCs were first reported in 2006, and human iPSCs were first reported in late 2007. Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cells from all three germ layers, and being able to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers.

Although additional research is needed, iPSCs are already useful tools for drug development and modeling of diseases, and scientists hope to use them in transplantation medicine. Viruses are currently used to introduce the reprogramming factors into adult cells, and this process must be carefully controlled and tested before the technique can lead to useful treatments for humans. In animal studies, the virus used to introduce the stem cell factors sometimes causes cancers. Researchers are currently investigating non-viral delivery strategies.

Non-embryonic (including adult and umbilical cord blood) stem cells have been identified in many organs and tissues. Typically there is a very small number of multipotent stem cells in each tissue, and these cells have a limited capacity for proliferation, thus making it difficult to generate large quantities of these cells in the laboratory. Stem cells are thought to reside in a specific area of each tissue (called a “stem cell niche”) where they may remain quiescent (non-dividing) for many years until they are activated by a normal need for more cells, or by disease or tissue injury. These cells are also called somatic stem cells.

— Bioengineering Applications of Engineered Heart Tissue —

  • Screening for drug discovery (i.e., pharmacodynamics) and cardiotoxicity testing
  • Cardiovascular disease modeling
  • Regenerative medicine: cell-based heart regeneration
    • Importance of avoiding arrhythmias
    • Immunological favorability
  • Evidence indicates that immunological tolerance to iPSC-derived tissues is favorable for utilization. Moreover, the evidence suggests that such tissues may actively participate in their own survival.

Examples of adult tissue-derived, pluripotent-derived stem cells

Cardiac progenitor cells naturally form functional, fully-fledged cardiomyocytes. However, harvesting suitable numbers of cardiac progenitor cells for the treatment of injured or failing myocardium is an insurmountable task via cardiac biopsy. For this reason, various adult stem cell sources have been identified from other human tissue, including bone marrow, adipose tissue, connective tissue, umbilical cord blood, and skeletal muscle. Notably, given these tissue types, stem cells induced from skeletal muscle present an intriguing opportunity for the treatment of debilitating myocardial ischemia that leads to myocardial infarction. In fact, stem cells associated with skeletal muscle cells are resistant to hypoxia, fibrosis, and easily achieve contractile characteristics (Tchao et al., 2013).

From myocyte to pluripotent-derived cardiomyocyte stem cell

Tchao et al. (2013) investigated the practicality of using human muscle cells (i.e., myocytes) for engineering cardiac muscle tissue by means of pluripotency induction given that cardiac and skeletal muscle share major transcription factors as well as sacromere proteins that are generally regarded as significant to either cardiac or skeletal muscle tissue but not both muscle types. In fact, skeletal muscle and cardiac muscle are known to have similar embryonic developmental pathways. What is more, according to Lewandowski et al. (2018), this similarity implies that skeletal muscle cells induced for pluripotency have what it takes to achieve greater myocardial development, compared to other tissue types, such as, for example, fibroblast cells from connective tissue.

The state of plasticity of a cell: review of Lewandowski et al.’s attempt to derive heart cells from muscle cells

In this section, we look closely at a study conducted by Lewandowski et al. (2018), who investigated the feasibility, significance, and practicality of cardiomyocytes derived from induced pluripotent stem cells of myogenic origin.

  • The work by Lewandowski et el. (2018):
  • Biochemical (regulatory) pathways and epigenetic memory
    • Importance of the Wnt signaling
    • Importance of the epigenetic memory
  • Morphological and functional properties, including electrophysiological analysis
    • Importance of mismatches between iPSC and native cardiac muscle cells
  • Paracrine effects
  • Study limitations

Cardiac muscle microarchitecture: innovative evaluation of stem cell therapy structural outcomes by cardiac DTI

Introduced in the mid-1990’s, diffusion tensor imaging (DTI) is a MRI technique capable of visualizing cardiac microstructure (Naumova & Yarnykh, 2014). One distinguishing feature of DTI is its ability to image fiber trajectories – a method known as tractography. Although tractography has been widely used in brain imaging (as well as musculoskeletal imaging), Sosnovik et al. (2014) recently published a landmark study showing the capacity of cardiac DTI tractography to characterize the integrity and spatial organization of cardiac myofibers in live mice after stem cell therapy for ischemic heart damage. According to Naumova and Yarnykh (2014):

The study [by Sosnovik et al. (2014)] establishes DTI as a new approach for assessment of the effect of stem cell therapy in a preclinical setting, in which it could prove whether cardiomyocytes derived from stem cells are actually aligned with host myofibers to regenerate heart structure and function. (p. 1720)

Furthermore, Naumova and Yarnykh (2014) stated the following:

Collectively, the present [study by Sosnovik et al. (2014)] and earlier studies have established the feasibility of DTI tractography in the human heart in vivo. However, a significant amount of work remains to translate this challenging technology to serial applications in clinical trial settings. (p.1721)

What is more, quality control protocols are a critical part of all imaging programs. With respect to protocols for cardiac DTI tractography, a dedicated phantom has only recently been developed that incorporates microtubules that allow the phantom to mimic the heart itself, specifically, the microarchitecture of the heart (Teh, Zhou, Hubbard Cristinacce, Parker, & Schneider, 2016). Testing of this phantom has been successful, and it is our conjecture that the device will help bring clinical trials utilizing serial cardiac DTI tractography a step closer to reality for assessment of the myocardium for patients with post-ischemic heart damage treated by regenerative stem cell therapy (preferably, pluripotent-derived cardiomyocytes).

Protein therapy in cardiology

Whereas protein engineering refers to various ways of modifying proteins, the benefit of protein therapy is its affinity for targeted interventions.

Protein-mediated paracrine effects identified through stem cell-derived cardiac muscle analysis, have spurred interest in protein therapy as a viable approach for cardiac muscle proliferation and myocardium repair (Jay & Lee, 2013).

Detecting artieral stenosis/occlustion: coronary angiography, coronary CT angiography, myocardial perfusion imaging, and reperfusion therapy and biomimicry

Conventional coronary angiography is the gold standard for detecting and treating coronary artery stenosis (Jiangping et al., 2013). Nevertheless, recent advances made in non-invasive, diagnostic methodologies, such as coronary CT angiography (with slice standards of 64 slices or greater) and myocardial perfusion imaging studies, are contributing to the earlier detection of the underlying pathology (i.e., earlier detection of coronary artery disease) (Gorenol, Schönermark, & Hagen, 2012; Tamarappoo et al., 2010). With respect to stress and rest myocardial perfusion imaging, according to Smith (2018):

If the coronary artery narrows less than 50% of the original vessel diameter, the effect on blood flow is clinically insignificant, but at 70% narrowing, blood flow is significantly affected during stress. During rest, the vessel must be narrowed 90% or more to reduce blood f low significantly. A cardiac event is not likely to be detected unless the coronary artery is narrowed to these degrees under stress or rest. Myocardial perfusion studies detect stress-induced myocardial schemia approximately 80% to 90% of the time, which is more sensitive than exercise electrocardiography at 60% to 70% sensitivity. This is because of the high rate of patients that undergo nondiagnostic exercise ECG tests because of baseline electrocardiographic abnormalities or inadequate stress.

What is more, a luminal stenosis at 70% to 80%, as assessed by coronary CT angiography, was correlated with electrocardiographic rhythm strips that revealed robust ST-segment depression (Lipinski, Morise, & Froelicher, 2002).

— Stents/Camouflaged Coating of Sugar —

Significant coronary artery narrowing is quantified as luminal narrowing at 70% or greater, although 50% narrowing is significant for the left main coronary artery (Bovin, Klausen, & Petersen, 2013). Given this percentage of narrowing (and the chronic nature of coronary artery disease), when cardiologists talk with patients and family members about reperfusion interventions, such as coronary artery ballooning and stenting, the discussion inevitably comes around to the likelihood of restenosis of treated vessels (including in-stent restenosis). One way to reduce the potential of in-stent restenosis, however, is a stent design that mimics the luminal lining of the tunica intima (the innermost layer of the coronary artery comprised entirely of endothelial cells) (Perez et al., 2009). In fact, such biomimetic-inspired stents have been modeled on the native coating found on endothelial cells of the tunica intima (i.e., the native glycocalyx). Production of these stents involves laser-etching technology that patterns the inside surface of the stent’s struts after these glycocalic fibers. This means that the surface area inside the stent effectually becomes camouflaged against vascular inflammatory and injury cycles that are associated with the patients’ coronary disease. The net-outcome for this design has reduced the body’s foreign body response to the stent.

monarch-caterpillar-cvcuFigure 2: The segmented structure of the monarch caterpillar has inspired a novel coronary stent concept that offers segmented movement relative to pulsatile blood flow through the coronary arteries, as well as movement related to the heart’s squeezing action.

— Stents/Dynamical, Flexible Cardionature and the Caterpillar’s Skeleton —

At rest, average heart rate is approximately 72 beats per minute, and with exercise, the typical range falls between 112 and 146 beats per minute. Therefore, we are clearly beneficiaries of the heart’s dynamical nature (including the constant movement of its surface) (Jiangping et al., 2013). What is more, the heart’s constant movement places high mechanical loads (i.e., mechanical stress and strain) on the functionality of stents, and this movement can ultimately damage the stent’s integrity. In their efforts to support the demands of this environment, Singh and Wang (2014) introduced a “flexible” stent that offers an unparalleled advantage over common, “stiff” stents. Their design mimics the flexible yet rigid skeletal structure of a monarch caterpillar. The end product is a biomimetic stent capable of flexing and bending with the movement of the heart, which, once again, is dynamical in nature as the heart adapts to the demands to supply oxygen to the body’s muscles and organs.

Endovascular angiography: reperfusion therapy and biomimicry

— Stents/High Shear Wall Flows and the Swirling Flow of Water Currents —

What about biomimicry in peripheral vascular studies? Has any attention been given to reperfusion therapy in this area of medicine? The answer to both of these questions is “yes.” For example, the superficial femoral artery (SFA) is a lower extremity artery susceptible to luminal narrowing secondary to atheromas and plaque build-up. Moreover, stents indicated for this vessel can be quite long, with lengths up to 15 cm commonly deployed. Recently, a novel stent design for the reperfusion of an occluded segment of the SFA was modeled on the flow of blood through the aorta, given that the aorta is quite resistant to atherosclerotic disease (Gaines, 2015). This intrinsic resistance identified with the aorta has been correlated with high-grade, pulsatile blood flow, which in part is also associated with the structural nature of the aortic arch. In other words, hemodynamics at the aorta not only imposes a high shear wall stress on the aorta’s inner wall (the tunica intima layer of this artery), but blood flow analysis reveals that the curvature of the aortic arch also helps give rise to a swirling, turbulent component of this high-grade, pulsatile flow.

TECHNICAL INSERT: For a conceptual image of the aforementioned dynamics in the healthy aorta, imagine that the turbulent and swirling nature of blood flow through the aortic arch repeatedly washes and rinses the luminal lining in this region of the artery. The best analogy comes from the flow of water that washes the banks along a somewhat sharp, curving bend (effectually, a U-turn) of a river as the current transits downstream.

With respect to the SFA, the stent that captures the nature of aortic blood flow has a subtle corkscrew design. Notably, such design helps impose a swirling effect on the flow of blood through the stented region of the SFA that also induces higher shear wall stress, which reduces the chances for in-stent restenosis.

— Stents/Vascular Smooth Muscle Cell Biomimetic Surface Patterns —

Because normal wound healing in the tissues surrounding a deployed stent is delayed, design schemes for stents have included antibody coatings to attract endothelial progenitor cells as a means to promote healing. However, testing of these stents has revealed that the associated lesions are often more complex than those associated with other stents, such as drug-eluting stents (whereas drug-eluting stents are known to be cytotoxic). Therefore, to address these challenges, and in a novel design twist to the aforementioned glycocalyx-mimicked stent, researchers recently introduced a stent that is designed to mimic vascular smooth muscle cells (VSMCs) at the nanometer level on the stent struts (Liang, et al., 2016). Methods similar to those used to obtain the glycocalic coating (i.e. laser-etching) were used to achieve the VSMC pattern. Testing performed on the iliac arteries of rabbits showed that a VSMC-biomimetic surface pattern was effective for rapid re-endothelialization (which translates as distinctly effective for promoting normal wound healing), as well as reducing the likelihood of in-stent restenosis.

Clearly the heart is uniquely designed! Can you imagine a career researching and developing engineered heart tissues?

The Heart is Uniquely Designed: Part of God’s Special Creation!

Quintessentially Mimicking the Structure and Function of the Human Heart:

Christian scholarship extending into professional roles is sincerely needed in education and culture, including mathematics and the sciences (including medicine). Chemical engineering and bioengineering can be a promising career for those who like to study physiology, microbiology, and biochemistry. And a well-developed understanding of anatomy and physiology plays a crucial role.

Insert: myocardial squeezing problem or atrial/ventricular filling problem

For many years echosonographers and cardiologists understood heart failure as a mechanical-type squeezing problem due to myocardial remodeling or enlargement; only recently did they learn it may also be a filling problem. The latter became known as diastolic heart failure.

As Christians, we ought to ask ourselves if we walk around with filling defects. In fact, the sermon “Why is my Heart not Filling?” given at Maranatha Baptist Church by Pastor Todd Grover (2018), gives us perspective on whether or not our own hearts might be suffering spiritually.

Consider 2 Corinthians 6:11-13 (ESV), in which the Apostle Paul expressed to the Christians living in Corinth: “We have spoken freely to you, Corinthians; our heart is wide open. You are not restricted by us, but you are restricted in your own affections. In return (I speak as to children) widen your hearts also.”

According to Pastor Grover (2018): “Here Paul revealed his heart’s condition to the Corinthians, that his heart is wide-open or enlarged, or that his heart is full and does not suffer from a filling problem.” Grover also pointed out that Paul stated he has spoken freely, and reminded listeners that Jesus said, “What comes out of the mouth proceeds from the heart.” However, Pastor Grover acknowledged that verse 11 of 2 Corinthians 6 is also clearly implying that Paul has a welcoming spirit toward the Corinthians, but not because Paul is outgoing, and has a warm and inviting personality. Rather, the reason is spiritual, since only a couple of years earlier Paul would have been killing these same Corinthians for their faith he is now trying to nurture.

So, a natural question to ask is what fills the heart. Some at Corinth were blaming Paul for their bad spiritual condition, but Paul is telling them that it is not he that should be blamed. Then, how did Paul’s heart become filled? To answer this, Pastor Grover quoted three verses from the very same epistle, and offered the applications of these verses, as follows:

  • The Spirit unveils, as we read according to 2 Corinthians 3:16 (ESV), “But when one turns to the Lord, the veil is removed.” Thus, if we don’t understand, then we can turn to the Lord, and the Lord will remove our veil of not understanding.
  • The Spirit writes, since we learn from 2 Corinthians 3:3 (ESV), “And you show that you are a letter from Christ delivered by us, written not with ink but with the Spirit of the living God, not on tablets of stone but on tablets of human hearts.” Therefore, we cannot live in the flesh and expect the Spirit to teach us.
  • Finally, the Spirit does not mix with sin, as we know according to 2 Corinthians 4:2 (ESV), “But we have renounced disgraceful, underhanded ways. We refuse to practice cunning or to tamper with God’s word, but by the open statement of the truth we would commend ourselves to everyone’s conscience in the sight of God.” And thus, we cannot allow sin to soil our hearts.

To summarize, Pastor Grover remarked: “So if our heart is not filling properly, we must develop a skill set as a Bible reader, because a heart fills as we read, learn, and know that the Spirit unveils, the Spirit writes, and the Spirit does not mix with sin.”

May the God of hope fill you with all joy and peace in believing, so that by the power of the Holy Spirit you may abound in hope.

– Romans 15:13 (ESV)

References

American Heart Association. (2016). Advanced cardiovascular life support: Provider manual. United States of America: First American Heart Association Printing.

Baldassarre, A.D., Cimetta, E., Bollini, S., Gaggi, G., & Ghinassi, B. (2018). Human-induced pluripotent stem cell technology and cardiomyocyte generation: Progress and clinical applications. Cells, 7(6), 48. [View in article] [View in PubMed]

Bovin, A., Klausen, I.C., & Petersen, L.J. (2013). Myocardial perfusion imaging in patients with a recent, normal exercise test. World Journal of Cardiology, 5(3), 54-59. [View in article] [View in PubMed]

Cremer, P., Hachamovitch, R., & Tamarappoo, B. (2014). Clinical decision making with myocardial perfusion imaging in patients with known or suspected coronary artery disease. Seminars in Nuclear Medicine, 44(4), 320-329. [View in PubMed]

Gaines, P.A., (2015). Biomimetic stents and the benefits of swirling flow. Endovascular Today, 6(3), 64-68. [View in article]

Gorenol, V, Schönermark, M.P., & Hagen, A. (2012). CT coronary angiography vs. invasive coronary angiography in CHD. GMS Health Technology Assessment, 2. [View in PubMed]

Grover, T. (Senior Pastor). [Maranatha Baptist Church Hayesville Ohio]. (2018, August 26). Why is my heart not filling? [Video file]. Retrieved from https://www.youtube.com/watch?v=ePPVUJpTDY4.

Hirt, M.N., Hansen, A., & Eschenhagen, T. (2014). Cardiac tissue engineering: State of the art. Circulation Research, 114(2), 354-367. [View in article] [View in PubMed]

Jay, S.M., & Lee, R.T. (2013). Protein engineering for cardiovascular therapeutics: Untapped potential for cardiac repair. Circulation Research, 113(7), 933-943. [View in article] [View in PubMed]

Jiangping, S., Zhe, Z., Wei, W., Yunhu, S., Jie, H., Hongyue, W., … Shengshou, H. (2013). Assessment of coronary artery stenosis by coronary angiography: A head-to-head comparison with pathological coronary artery anatomy. Circulation: Cardiovascular Interventions, 6, 262-268. [View in article] [View in PubMed]

Lewandowski, J., Rozwadowska, N., Kolanowski, A.M., Malcher, A., Zimna, A., Rugowska, K.F., … Kurpisz, M. (2018). The impact of in vitro cell culture duration on the maturation of human induced pluripotent stem cells of myogenic origin. Cell Transplantation, 27(7), 1047-1067. [View in article] [View in PubMed]

Liang, C., Hu, Y., Wang, H., Xia, D., Li, Q., Zhang, J., …, Dong, M. (2016). Biomimetic cardiovascular stents for in vivo re-endothelialization. Biomaterials, 103, 170-182. [View in PubMed]

Liau, B., Zhang, D., & Bursac, N. (2012). Functional cardiac tissue engineering. Regenerative Medicine, 7(2), 187-206. [View in article] [View in PubMed]

Lipinski, M., Morise, A., & Froelicher V. (2002). What percent luminal stenosis should be used to define angiographic coronary artery disease for noninvasive test evaluation? Annals of Noninvasive Electrocardiology, 7(2), 98-105. [View in PubMed]

National Institute of Health website. (n.d.). Stem cell information glossary. Retrieved from https://stemcells.nih.gov/glossary.htm.

National Institute of Health website. (n.d.). Where do stem cells come from? Retrieved from https://stemcells.nih.gov/info/faqs.htm#whatare.

Naumova, A.V., & Yarnykh, V.L. (2014). Assessment of the heart microstructure: From mouse to man. Circulation, 129(17), 1720-1722. [View in article] [View in PubMed]

Perez, G., Rodriguez-Granillo, A.M., Mieres, J., Llaurado, C., Rubilar, B. Risau, G., … Rodriguez, A.E. (2009). New coating stent design for patients with high-risk coronary lesions for thrombotic events: early and long-term results of the Camouflage registry. Journal of Invasive Cardiology, 21(8), 378-382. [View in PubMed]

Purdom, G. (2007, January 1). Stem cells: Does their origin matter? Answers Magazine. [View in online article]

Singh, C., & Wang, X. (2014). A biomimetic approach for designing stent-graft structures: Caterpillar cuticle as design model. Journal of the Mechanical Behavior of Biomedical Materials, 30, 16-29. [View abstract] [View in PubMed]

Sled, E. (2018). Biblical integration in anatomy and physiology: A design approach. Answers Research Journal, 11, 141-148. [View in article]

Smith, R. (2018). Myocardial perfusion study to detect coronary artery disease. Radiologic Technology, 90(2), 131-144. [View in PubMed]

Sosnovik, D.E., Mekkaoui, C., Huang, S., Chen, H.H., Dai, G., Stoeck, C.T., … Liao, R. (2014). Microstructure impact of ischemia and bone marrow-derived cell therapy revealed with diffusion tensor magnetic resonance imaging tractography of the heart in vivo. Circulation, 129(17), 1731-1741. [View in article] [View in PubMed]

Tamarappoo, B.K., Gutstein, A., Cheng, V.Y., Nakazato, R., Gransar, H., Dey, D., … Berman, D.S. (2010). Assessment of the relationship between stenosis severity and distribution of coronary artery stenosis on multislice computed tomographic angiography and myocardial ischemia detected by single photon emission computed tomography. Journal of Nuclear Cardiology, 17(5), 791-802. [View in PubMed]

Tchao, J., Jin Kim, J., Lin, B., Salama, G., Lo, C.W., Yang, L., & Tobita, K. (2013). Engineered human muscle tissue from skeletal muscle derived stem cells and induced pluripotent stem cell derived cardiac cells. International Journal of Tissue Engineering, 198762. [View in PubMed]

Teh, I., Feng-Lei, Z., Hubbard Cristinacce, P.L., Parker, G.J.M., & Schneider, J.E. (2016). Biomimetic phantom for cardiac diffusion MRI. Journal of Magnetic Resonance Imaging, 43(3), 594-600. [View in article] [View in PubMed]

Wininger, K.L. (2018, September 14). Biomimicry 101: Biomaterials and tissue engineering. [blog post]. Retrieved from https://studiesoncreation.org/2018/09/14/biomimicry-101-biomaterials-and-tissue-engineering/.

Previous articles in this series:

Other medical applications are featured in the next installment in our biomimicry series!

In our next installment on biomimicry, we will touch finally on cardiac function and fractal behavior via the area of concentration we have coined mathematical cardiology. We then move forward from our focus on the heart, as we turn our attention to two unrelated fields in medicine where biomimetic solutions have garnered exciting outcomes: diabetic solutions and work towards spinal cord regeneration.

Biomimicry 101: Cardiovascular Medicine: Part 1: Thinking Outside the – Stem Cell – Box

anat-stent-ekg-monarch-caterpillarFigure 1: Anatomy of the heart, with blood flow schematic (top left panel); profile of a coronary artery stent application (top right panel); the electrocardiogram – abbreviated ECG or EKG – representing the heart’s conduction system (center panel); and the monarch caterpillar (bottom panel).

When you ponder biomimicry, think design, intelligent design, and creation, but please don’t think evolution. And when considering biomimetic applications, let your imagination know no bounds.

The previous article in our biomimicry series introduced several key issues describing the feasibility and use of engineered tissue in different health and medical fields. Presently, this article (in two installments) will focus on various examples concerning bioengineering and biomimicry in the field of cardiovascular medicine. For example, we address the ethics and challenges concerning the regeneration of cardiac tissue via stem cell therapy. At the same time, however, we draw the spotlight away from a stem cell model to survey other novel clinical cardiology and endovascular biomimetic research. What is more, a first principle that continues to serve as motivation for exploring biomimetic applications that deal with cardiac tissue is our viewpoint that the heart is uniquely and deliberately designed, as emphasized with respect to tissue scaffolds in our prior article, as follows:

Because of the unique makeup of cardiac tissue, the work surrounding cardiac tissue scaffolds has focused on mimicking the physiological properties of the heart itself. This fact is true whether we are talking about designing artificial heart valves that mimic the mechanical properties of native heart valve tissue (Capulli et al., 2017), or boldly seeking to engineer myocardial tissues that elicit the unique mechanical, biological, and electrical properties existing at cell-tissue interfaces throughout the heart (Kaiser & Coulombe, 2015). (“Three examples of biomimicry applied to tissue engineering,” para. 3)

Once again, the aim of this series, and in particular this subject matter, is to bring glory to God and His creation, which includes human beings as a special creation. We begin our discussion with an overview on heart anatomy and physiology.

Anatomy and physiology of the heart

Tissues that make up the heart integrate a distinct blend of mechanical, biological, and electrical properties. To best examine these properties, we first review this unique organ.

— Location, Location, Location —

The heart is centered within the chest cavity, just left of midline between our two lungs. In fact, our bodies accommodate its exact location because our left lung is comprised of only two lobes, whereas our right lung has three. This means our hearts are nuzzled into the space made available by the “missing” part of our left lung. What is more, an intimate vascular network exists between our heart and lungs, and when taken together these organs and their connections comprise our cardiopulmonary system (i.e., the heart-lung system).

— Circulation —

Our circulatory system, which includes the associated vasculature of the heart, is a closed-loop system that is responsible for moving blood through our bodies. With the heart serving as the system’s pump, there are three types of blood vessels: the arteries, the capillaries, and the veins.

  • Arteries are specialized blood vessels composed of three individualized layers: the innermost layer, the tunica intima; the middle layer, the tunica media; and the outermost layer, the tunica adventitia. Within the tunica media are smooth muscles that control the diameters of arteries via influence of the autonomic nervous system. Arteries function as conduits that, in all but one circumstance, carry oxygenated blood away from the heart. In addition, healthy arteries are well-known for their resilient, elastic nature. A very large artery known as the aorta is the first artery in the circulatory system.
  • Capillaries facilitate the exchange of oxygen, nutrients, and waste by-products resulting from cellular respiration and metabolism.
  • Veins are characterized by their one-way valves that help direct blood flow toward the heart (and thus prevent the back-flow of blood).

— The Big Squeeze —

The heart’s squeezing action is what circulates blood throughout our vasculature. What is more, a heart cycle is easily detected via the heart’s squeezing sounds, the so-called lub-dub sound of the heart. The lub sound represents simultaneous contraction of the two top chambers (i.e., the atria), and the dub sound represents simultaneous contraction of the two bottom chambers (i.e., the ventricles). Blood has four main components: oxygen-carrying cells called red blood cells; functional immunity cells called white blood cells; cell fragments that are important for clotting called platelets; and a liquid constituent called plasma. What follows is the path our blood takes within the cardiopulmonary system:

  • After a red blood cell releases its oxygen content to our muscles and organs, it is called deoxygenated. Deoxygenated red blood cells, together with the aforementioned constituents, make their way back to the heart through our systemic venous system (i.e., our veins). As this pathway draws closer to the heart, it converges to form two large venous trunks known as vena cava. The superior vena cava brings back blood from the upper part of the body, and the inferior vena cava brings back blood from the lower part of the body. This returning systemic flow of blood then enters the first of our heart’s four chambers – the right atrium.
  • Once inside the right atrium, blood passes through the tricuspid valve into the second chamber of the heart – the right ventricle. This occurs in synchrony with the first of the two squeezing sounds, the so-called lub sound associated with atrial contraction.
  • As a result of ventricular contraction (i.e., the dub sound), the blood then passes from the right ventricle through the pulmonary semi-lunar valve and flows toward our lungs via both pulmonary arterial trunks, the right and the left pulmonary arteries. The pulmonary arteries carry the blood to the lungs where red blood cells are oxygenated within the lung’s capillary beds. The oxygenated blood will now flow back towards the heart by way of the pulmonary veins, a process returning this pulmonary flow of blood to the heart’s third chamber – the left atrium.
  • Once in the left atrium, the blood passes through the mitral valve into the fourth and final chamber of the heart – the left ventricle. Again, this occurs in synchrony with atrial contraction.
  • Finally, with contraction of the left ventricle, the oxygenated blood enters systemic circulation as it passes through the aortic semi-lunar valve (i.e., flowing out of the left ventricle and into the aorta).

TECHNICAL INSERT: Arteries and veins are recognized by the directional flow of blood that they facilitate away from – or toward – the heart, respectively, and not by whether or not the blood within the artery or vein is oxygenated or deoxygenated.

What is more, each squeezing action initiating a new cardiac cycle will simultaneously generate a pressure spike within our vessels, causing the blood to effectually pulsate through the circulatory system. Notably, this spike or wave of pressure is called systole, whereas the underlying pressure is referred to as diastole. Both systole and diastole make up our body’s systemic blood pressure. Normal systemic systolic pressure is 120 mmHg, and normal systemic diastolic pressure is 80 mmHg.

The term that describes the volume of blood pumped through the body is cardiac output, and this volume is seen as a marker of efficiency of cardiac mechanics and hemodynamics. To adequately deliver oxygen to our body’s tissues (called perfusion), cardiac output is approximately five liters per minute. In fact, investigations looking into cardiac output during cardiopulmonary resuscitation (CPR) led to guidelines from the American Heart Association to favor compression-only CPR to better achieve adequate blood flow and perfusion (Wininger, 2007). Investigators discovered that two different theories describing CPR-related chest compression – the cardiac pump theory and the thoracic pump theory – actually work together and in tandem depending on the physiological situation. One study helping investigators reach this level of insight was a review of the use of CPR for emergent care during coronary angiography. Today, there are even mechanical chest compression devices that heart catheterization labs can use, if necessary, during interventional care (Wagner et al, 2010).

Perspectives such as this illuminate how far we have come. Currently, a prototype of a ventricular assist device that mimics the natural squeezing/compression action of the heart has proven feasible. The device is a soft robotic sleeve that wraps around the heart, and it is being devised for those patients with severe heart failure (Roche et al, 2017). A major benefit of this particular device is that it never contacts blood, unlike traditional assistive devices, and thus eliminates the need for patients to be on blood thinners for prolonged periods of time.

— The Conduction of Electricity: The Conduction Pathway —

Cardiac squeezing action is controlled by the heart’s electrical activity. In fact, the conduction pathway that exists for this electrical activity is what we observe when looking at electrocardiogram tracings (abbreviated ECG, or colloquially known as EKG rhythm strips). ECG tracings show three main waves: the P-wave, the QRS-complex, and the T-wave. Crucially, analysis of these waves provides cardiologists with critical diagnostic information. The conduction pathway begins in the right atrium with a group of “like-minded” heart cells known as the sinoatrial node (abbreviated SA node and also called the heart’s “pacemaker cells”). Once the SA node fires, electrical charge disperses across the atrium and arrives at the aterioventricular (AV) node. At the AV node, the electrical charge then travels down through the intraventricular septum (a tissue that separates the chambers associated with the left and right ventricles), traveling down and along the bundle of His.

Continuing on – the charge follows the pathway that is made available by the bundle of His, a fibrous tissue pathway that splits within the septum and forms a right bundle branch and a left bundle branch. Here the electrical charge flows through the right and left bundle branches within the septum. Finally, both the right and left bundle branches divide and carry the electrical charge into terminal filaments of delicate, feathery-like fibers called Purkinje fibers.

The conduction pathway within the heart, not to mention the heart itself, is an electrochemical process. In fact, a physiological redundancy has been designed into the cardiac electrical system. By this I mean that the heart’s muscle cells, the cardiac myocytes, have the capacity to fire at sustained rates, and thus each contract individually on their own accord. However, specified regions exist throughout the myocardium, as well as along the conduction pathway, that are designed to fire in a hierarchal fashion, with each region firing at determined rates and led by the SA node, or in other words, the so-called pacemaker cells.

— The Arteries That Crown the Heart —

Coronary arteries are special arteries that crown the heart. These arteries are important because they provide the heart with oxygen so that it pumps effortlessly. Notably, all coronary arteries stem from two main divisions, aptly named the right coronary artery and the left main coronary artery. Of these two divisions, the left main coronary artery further divides into the left anterior descending artery and the left circumflex artery (with the latter known simply as the circumflex artery). However, the coronary arteries are important not only because they supply the heart with oxygen, but because they are also susceptible to inflammation and injury that may lead to an occlusive artery disease known as coronary artery disease, a condition that restricts oxygen delivery.

Coronary artery disease is a silent, chronic process that has two phases. The first phase begins when white blood cells respond to inflammation between the innermost and middle layers (the tunica intima and tunica media layers, respectively) of one or more of the coronary arteries. As more and more white blood cells arrive, over time they form a viable bump called an atheroma within the inner wall (i.e., the luminal lining) of the affected artery. If the surface of the lumen over the bump bursts, then the second phase of coronary artery disease is initiated. In the second phase, the rupture or burst triggers platelets to aggregate around the injured tissue in an attempt to clot off the injury. In fact, this clot formation is called a thrombus. If the clot (or thrombus) significantly occludes the vessel, or if the clot formation occludes the vessels at just the right place within the coronary artery vasculature, a person may suffer from a heart attack. Heart attacks are a life threatening situation because the surrounding heart tissue, or the so-called mycocardium, that is normally supplied with oxygen by the flow of blood from the effected artery, will no longer receive its supply.

TECHNICAL INSERT: The lumen of the artery (i.e., the inner passageway of the artery) is characterized by a clean, smooth lining. This luminal lining is made up of endothelial cells, and it is these cells themselves that compose the innermost arterial layer (i.e., the tunica intima). This layer is much more delicate compared to the middle and outermost layers, the tunica media and the tunica adventia, respectively. Notably, the tunica media contains bands of smooth muscle, whereas the tunica adventia contains connective tissue. However, all three layers play an important role in the elastic nature of all arteries, but in the coronary arteries particularly.

One of the best ways to guard against coronary artery disease is to observe Virchow’s triad. Although a comprehensive exam of the three aspects of Virchow’s triad is beyond the scope of this article, it is interesting to note that the prevention of endothelial injury, or the reduction of endothelial dysfunction, is plausible through proper diet and exercise. When taken together, proper diet and adequate exercise can reduce or even counteract the inflammatory process that endothelial cells endure. And again, endothelial cells are those cell types that make up the tunica intima layer of arteries, and thus, it is these cells that are responsible for the smooth luminal lining of coronary arteries (i.e., the smooth inner-wall of the passageway of an artery).

virchow's-triadFigure 2: The three sides of Virchow’s triad.

And, indeed, diet and exercise are important since a luminal narrowing of 20%, as evidenced by coronary catheterization studies, is considered normal (Bovin, Klausen, & Petersen, 2013). What is more, studies show that between 30% – 50% of patients undergoing coronary CT angiography can have a stenosis (or a luminal narrowing) of up to 50% and not indicate signs of ischemic disease detectable by myocardial perfusion imaging, such as SPECT imaging (Cremer, Hachamovitch, & Tamarappoo, 2014).

— The Husk of Life: Glycocalyx —

The word glycocalyx is shaped from the prefix glyco or “sweet” and the suffix kalyx or “husk.” Because the glycocalyx forms a sugary, slimy coating of certain cell types in various animals, as well as several different cell types of the human body, we may think of it as the sweet husk (i.e., coating) of life. What is more, the prefix refers to the coating’s composition, which is carbohydrate-based. Microscopically, gylcocalyx looks like feathery fibers. First-year anatomy and physiology students would recognize the coating as the feathery elements of the microvilli of our intestinal tracts (recalling that the microvilli are actually the lining of the villi). However, important for our purposes, a glycocalyx coating is present on the innermost layer of our vasculature (i.e., on the luminal surface of the endothelial cells that comprise the tunica intima). In fact, a protective barrier made up of glycocalic fibers functions as a vital component to our cardiovascular health (Sieve, Munster-Kuhnel, & Hilfiker-Kleiner, 2018). Moreover, researchers investigating the embryonic stages of certain bird species have shown that a glycocalyx layer is present and viable as soon as blood flow starts (Henderson-Toth, Jahnsen, Jamarani, Al-Roubaie, & Jones, 2012).

For you formed my inward parts; you knitted me together in my mother’s womb. I praise you, for I am fearfully and wonderfully made. Wonderful are your works; my soul knows it very well.

– Psalm 139:13,14 (ESV)

— A Unique Thing About Cardiac Myocytes: The Heart’s Muscle Cells —

From organ to tissue to the cellular level, the cardiac myocytes are rather specialized muscle cells. According to Ferrari’s comprehensive review (2002) of these cells:

The myocytes are extraordinary cells. They are immortal and contract for a lifetime, supporting the peripheral circulation. In order to do so, they have a unique ultrastructure and unique biochemical machinery that allows them to produce enough adenosine triphosphate to support the contraction. This article deals with the ultrastructure of cardiac muscle and myocytes, and with our current understanding of cardiac metabolism. In addition, the process of contraction is taken into consideration, as well as the mechanisms that allow the adult myocyte to be a terminal cell. However, even the myocytes can die; this can happen by necrosis as a result of an external insult (e.g. a lack of oxygen due to an abrupt occlusion of a coronary artery) or by apoptosis – a genetically programmed type of death that is operative in foetal life. Interestingly, and quite amazingly, under pathological conditions such as acute myocardial infarction or congestive heart failure, this genetic programme is reinstated and apoptosis can then occur, thus resembling features that occur in the embryonic phenotype. The metabolic alterations that occur under pathological conditions such as myocardial ischaemia are also addressed in depth, with several references to the so-called ‘new ischaemic syndromes’, such as stunning, hibernation and reperfusion paradox. The review is presented in light of an understanding of the biochemical and biomolecular changes that occur in pathological conditions, with the hope that this will provide room for innovative therapeutic intervention.

Thinking outside the embryonic stem cell box

In her 2007 article “Stem Cells: Does Their Origin Matter?” published in Answers Magazine, Dr. Georgia Purdom, a molecular geneticist with Answers in Genesis, presented several key points:

  • Stem cells are classified as either totipotent or pluripotent/multipotent.
  • Totipotent stem cells are taken from embryonic tissue, an action that kills the embryo in the process. These cells are capable of forming any cell type in the body, but carry certain risks for the recipient.
  • Pluripotent and multipotent stem cells are harvested from adult tissue, and notably, the process does no harm to the adult. These stem cell types are capable of forming almost every cell type in the body.
  • Ethical issues concerning life and its preservation can be easily reconciled through a biblical worldview.
  • Interestingly, an alternate approach to using embryonic stem cells taps the potential to reprogram adult cells to become more like embryonic stem cells. Here Dr. Purdom cited the work by Silva, Chambers, Pollard, and Smith (2006) with the protein Nanog on nervous system cells, published in the journal Nature.

Optimistic remarks concerning the reprogramming of adult cells surfaced ten years later in an interview with acclaimed materials scientist Buddy Ratner, PhD of the University of Washington. The interview appeared in a 2017 issue of the biotechnology journal Future Science, and celebrated Dr. Ratner’s forty-nine years of work in biomaterials science. When asked about exciting advances we should look for in the next five years within the biomaterials arena, Dr. Ratner’s response touched on the plasticity of adult cells. What follows is the relevant excerpt of that interview:

Another interesting area is a new concept I call ‘cell plasticity’. Through most of Modern Biology we have used the term ‘terminally differentiate’ – a mature cell cannot go any place. Now people are getting the idea that cells are actually very plastic, they change from one cell type to another, and the ability to control these transformations means almost any cell has a stem cell-like ability. We do have defined stem cells but I think the ability to take an adult cell and to crank it back to a more plastic, stem-like state, then direct it, gives us tremendous options in the area we call regenerative medicine. Within the initial biomaterials ideas we said ‘well if a part fails we’ll replace it with plastic and metal’ – the regenerative medicine field says ‘if a part fails we’ll just regrow it’. Regenerative medicine interest is increasing and efforts in that area are rightly accelerating. The interesting thing is, this still requires an extensive use of biomaterials in many different forms such as scaffolds and drug delivery platforms, so biomaterials are an important foundation technology to make regenerative medicine a reality. (“Question #5,” para. 2)

Part 2 will focus on biomimetic applications in cardiovascular medicine!

Keeping the preceding paragraphs in mind, we now outline the second installment of our focus on cardiovascular medicine (part two of our article) in this biomimicry series. First, discussion related to tissue engineering and regenerative science in cardiovascular research will center specifically on multipotent and pluripotent stem cell therapy. Second, we will briefly expand on cell plasticity related to cardiovascular medicine. Third, we will draw attention to the interesting, evolving role of protein therapy in cardiology, such as efforts to treat heart attack (i.e., myocardial infarction) by reprogramming/regenerating heart muscle cells (i.e., the cardiac myocytes). Fourth, we will highlight a novel approach to reperfusion therapy by Singh and Wang (2014), who introduced the concept of using coronary artery stents mimicked after the skeletal structure of the monarch caterpillar. Finally, we will explore a variety of other biomimetic applications that have promising potential to impact cardiac and endovascular patient care.

monarch-caterpillar-cvcuFigure 3: The segmented structure of the monarch caterpillar has inspired a novel coronary stent concept that offers segmented movement relative to pulsatile blood flow through the coronary arteries, as well as movement related to the heart’s squeezing action.

References

Bovin, A., Klausen, I.C., & Petersen, L.J. (2013). Myocardial perfusion imaging in patients with a recent, normal exercise test. World Journal of Cardiology, 5(3), 54-59. [View in article] [View in PubMed]

Cremer, P., Hachamovitch, R., & Tamarappoo, B. (2014). Clinical decision making with myocardial perfusion imaging in patients with known or suspected coronary artery disease. Seminars in Nuclear Medicine, 44(4), 320-329. [View in PubMed]

Ferrari, R. (2002). Healthy versus sick myocytes: Metabolism, structure and function. European Heart Journal Supplements, 4 (supplement G), G1-G12. [View in article]

Henderson-Toth, C.E., Jahnsen, E.D., Jamarani, R., Al-Roubaie, S., & Jones, E.A. (2012). The glycocalyx is present as soon as blood flow is initiated and is required for normal vascular development. Developmental Biology, 369(2), 330-339. [View in article] [View in PubMed]

Purdom, G. (2007, January 1). Stem cells: Does their origin matter? Answers Magazine. [View in online article]

Ratner, B. (2017). Forty-nine years in Biomaterials Science: An interview with Buddy Ratner. Future Science OA, 3(1), FSO158. [View in article] [View in PubMed]

Roche, E.T., Horvath, M.A., Wamala, I., Alazmani, A., Song, S.E., Whyte, W., … Walsh, C.J. (2017). Soft robotic sleeve supports heart function. Science Translational Medicine, 9(373), eaaf3925. [View abstract] [View in PubMed]

Sieve, I., Munster-Kuhnel, A.K., & Hilfiker-Kleiner, D. (2018). Regulation and function of endothelial glycocalyx layer in vascular diseases. Vascular Pharmacology, 100, 26-33. [View in article] [View in PubMed]

Silva, J., Chambers, I., Pollard, S., & Smith, A. (2006). Nanog promotes transfer of pluripotency after cell fusion. Nature, 441, 997-1001. [View abstract] [View in PubMed]

Singh, C., & Wang, X. (2014). A biomimetic approach for designing stent-graft structures: Caterpillar cuticle as design model. Journal of the Mechanical Behavior of Biomedical Materials, 30, 16-29. [View abstract] [View in PubMed]

Wagner, H., Terkelsen, C.J., Friberg, H., Harnek, J., Kern, K., Lassen, J.F., & Olivecrona, G.K. (2010). Clinical arrest in the catheterization laboratory: A 5-year experience of using mechanical chest compressions to facilitate PCI during prolonged resuscitation efforts. Resuscitation, 81(4), 383-387. [View abstract] [View in PubMed] [View in article]

Wininger, K.L. (2007). Chest compressions: biomechanics and injury. Radiologic Technology, 78(4), 269-274. [View abstract] [View in PubMed]

Wininger, K.L. (2018, September 14). Biomimicry 101: Biomaterials and tissue engineering. [blog post]. Retrieved from https://studiesoncreation.org/2018/09/14/biomimicry-101-biomaterials-and-tissue-engineering/.

Previous articles in this series:

Stay tuned as we continue our focus on cardiovascular medicine!

In our next installment, we not only continue our discussion on cardiac tissue engineering, but we will also highlight novel biomimetic applications across various areas of clinical cardiology and endovascular research.

Biomimicry 101: Biomaterials and Tissue Engineering

mother-of-pearlBeads of nacre, also known as mother of pearl

When you ponder biomimicry, think design, intelligent design, and creation, but please don’t think evolution. And when considering biomimetic applications, let your imagination know no bounds.

This installment in our series on biomimicry examines biomaterials and tissue engineering, with an emphasis on the foreign body response and normal wound healing. This subject matter is intended to glorify God and His creation, which includes human beings as a special creation.

Biomaterials

A biomaterial may be thought of as engineered material (derived synthetically or naturally-occurring) placed into the body to minimize loss of structure and function. In some cases a biomaterial may be referred to as a biomedical material. In fact, The Williams Dictionary of Biomaterials (1999) defines a biomaterial as “material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body” (p. 42). Examples of the body systems where medical implants can be applied include the following:

  • Skeletal system—joint replacements, bone cement, bony defect repair, artificial tendon/ligament, and dental implants
    • Mollusk shells, such as oyster shells and mussel shells, have been studied as biomineralization models. In fact, the inner lustrous lining of shells such as oysters is nacre, otherwise known as mother of pearl (Luz and Mano, 2009).
  • Cardiovascular system—blood vessel prosthesis (grafts or stents), heart valves, implantable generators (pacemakers, defibrillators, and cardiac resynchronization therapy devices)
  • Organs—artificial heart, artificial kidney, artificial pancreas, and skin templates
  • Senses—neuromodulation stimulators (cochlear implants, and deep brain or spinal cord stimulators), intraocular lenses, contact lenses, implantable seizure-detection devices, and pain pumps

The goal of biomaterials science is to achieve biocompatibility. The Williams (1999) definition of biocompatibility is “the ability of a material to perform with an appropriate host response in a specific application” (p. 40). This implies survival of the material in a tissue matrix without causing significant inflammation or irritation on an ongoing basis. A truly biocompatible material would promote little-to-no such effects. Despite advances in technology, however, all currently available biomaterial implants are viewed by the body as foreign objects, also called foreign bodies. Foreign body implants trigger the body’s foreign body response, which is a protective immunological response that occurs in several steps. The final step is encapsulation, a process that effectually walls off the implant with strands of fibrous, connective tissue.

— Immunogenicity and the Foreign Body Response —

The term immunogenicity describes the likelihood of a foreign object triggering an immune response, such as the foreign body response. What follows is a synopsis of the foreign body response to an implant:

  • First, neutrophils (a type of white blood cell) and tissue react to the implant by a process known as the inflammatory reaction. Simultaneously, certain proteins cover the surface of the implant with a thin film. These proteins also serve as signaling agents and markers, and are collectively known as matricellular proteins (Ratner, 2001).
  • Second, the inflammatory reaction can bring macrophages (a type of white blood cell) to the implant site. However, whether or not the macrophages are able to successfully engulf and extrude the foreign body determines the next step.
    • Neutrophils and macrophages are the two types of white blood cells of most importance in the scope of this discussion. White blood cells are also known by their group name leukocytes.
  • Third, in most, if not all cases of implanted foreign bodies, like those intended as medical devices and implants, macrophages are unable to extrude them. Consequently, the macrophages coalesce around the implant to form multi-nucleated giant cells, which act to encase the implant in granulated tissue called a granuloma. Over time, because of its fibrous connective tissue capsule, the granuloma effectually walls off the implant.
    • Figure 1 in the aforementioned article by Wininger, Bester, & Deshpande (2012) shows three locations, after time, where fibrous capsules are most likely to develop with an implantable spinal neurostimulator. These locations are the epidural space, the incision site for the tunneled lead wires, and the gluteal pocket that accepts the rechargeable battery. Figure 2 in the same article is the fluoroscopic image showing the lead wires in the epidural space of the thoracic spine. Again, the article examines the medical necessity and benefits of the application, and outlines how the benefits outweigh the risks in the case presented.

— Foreign Body Response: Fibrous, Connective Tissue Capsule —

Tissue encapsulation is the primary long-term defense to a foreign body implant. However, tissue encapsulation ultimately impacts the usefulness of the implant. In many cases, the thickness of the capsule plays a major role, with thicker capsules being more detrimental to the effectiveness of some implants than thinner ones around the same device type. Regardless of capsule thickness, however, the interface between the implant and tissue will encounter ongoing macrophage activity, which can be detrimental to the success and longevity of certain types of implants. For instance, osteoclasts (a macrophage-related cell associated with bony tissue) can eat away at bone adjacent to the surface of orthopedic implants, and thus loosen the integrity of the application.

A better understanding of the foreign body response, especially the factors that determine the thickness of fibrous tissue encapsulation, is an active area in biomaterials research. According to Anderson (2004):

The form and topography of the surface of the biomaterial determine the composition of the foreign-body reaction. With biocompatible materials, the composition of the foreign-body reaction in the implant site may be controlled by the surface properties of the biomaterial, the form of the implant, and the relationship between the surface area of the biomaterial and the volume of the implant. (p. 311)

Given the importance of the foreign body response and the consequences of tissue encapsulation, the role of the macrophage cannot be overestimated. In fact, researchers have discovered numerous macrophage phenotypes involved in both the foreign body response and normal wound healing (Kohl and DiPietro, 2011).

— A Closer Look: Normal Wound Healing —

In normal wound healing, “neutrophils and macrophages clean the wound site of bacteria, debris, and damaged tissue” (Ratner, 2001, p. 1343). Within this setting, macrophages along with other cells reconstruct the site with vascularized tissue. Noticeably, as part of the reconstruction and revascularization phases, numerous proteins, again, collectively called matricellular proteins, are involved. However, once a wound is healed (i.e., a vascularized network is achieved), the matricellular proteins are no longer needed, and they vanish from the wound site.

What is more, some suggest the matricellular proteins play the key role in the applications of implanted biomaterials. According to Ratner (2001), “an understanding of the matricellular proteins involved in wound healing suggests novel surface modification approaches to improve the performance of implants, including endosseous devices” (p. 1343).

All of this leaves us with the impression that the supportive tissue around a medical implant site, including the cells adjacent to the site, plays a crucial role. This zone contains the extracellular matrix.

— The Extracellular Matrix and the Idea of Tissue Scaffolds —

Apart from blood, all cells in the human body reside within what is called the extracellular matrix. Chan and Leong (2008) reviewed five functions of the extracellular matrix:

  • Structural support for cells (i.e., a physical environment for cells)
  • Mechanical properties that are associated with normal tissue function, such as rigidity and elasticity
  • A regulatory function that provides cues for residing cells to regulate their activities
  • A growth factor reservoir that helps to regulate the activities of these factors
  • A degradable physical environment not only for new vascularization, but also for remodeling. This plasticity is a response to developmental, physiological, and pathological changes during tissue morphology, homeostasis (i.e., maintenance of equilibrium), and wound healing, respectively.

From a functional point of view, a tissue scaffold is the bioengineered analog of the extracellular matrix. What is more, O’Brien (2011) describes tissue scaffolds as one part of a three-pronged approach to tissue engineering. The remaining two prongs are the cells and the growth factors/bioreactor.

The concept of tissue engineering

In the late 20th century, the process of fabricating tissue in the laboratory became known as tissue engineering, and this effectually caused a paradigm shift in reconstructive surgery (Bell, 2000).

  • This exact argument can be made for regenerative medicine, which is a subject explored in greater detail later in this series. However, for now we may consider regenerative medicine as a branch of medicine that attempts to improve structure and function at the biological tissue level, and very often at the cellular level. Ultimately, the purpose is to prevent deficits that can lead to functional impairments at the organ and whole-body levels. In fact, the goals of tissue engineering, regenerative medicine, and even biomaterials, are closely related: minimize loss of (or attempt to improve) structure and function. What is more, because of the importance of minimizing loss, particularly functional loss at the whole-body level, the notion of regenerative rehabilitation has become a meaningful issue within the field of physical therapy to assist patients in improving their functional capacity.

Three examples of biomimicry applied to tissue engineering

Bone/nacre scaffolds

With respect to biomimicry and bony tissue engineering, no other material has been examined as intensely as nacre. This is because of nacre’s inherently high biocompatibility. What is more, the mechanical properties of nacre have also played a role in its investigation as a viable biomimetic. Nacre, as a biomineral, has a consistent hierarchal structure of mineral layering (Kakisawa & Sumitomo, 2011, and Luz & Mano, 2009). The use of nacre has been investigated in dental, oral and facial surgery, as well as various orthopedic applications (Gerhard et al., 2017, and Ratner, 2001). In fact, in recent years, biomimetic dentistry has emerged as a branch of dentistry, and nacre organic matrix extract has been used for enamel remineralization (Green, Lai, & Jung, 2014).

Bone/marine sponge collagen scaffolds

A recent approach in the development of a biocompatible bony matrix centers on the feasibility of modeling the marine sponge. Interest in developing sponge-based matrices exists because of the diversity in the types of sponges available and because of the porous properties of their skeletal frameworks that invite cellular infiltration (Green, Howard, Yang, Kelly, & Oreffo, 2003).

Heart/cardiac tissue engineering

Because of the unique makeup of cardiac tissue, the work surrounding cardiac tissue scaffolds has focused on mimicking the physiological properties of the heart itself. This fact is true whether we are talking about designing artificial heart valves that mimic the mechanical properties of native heart valve tissue (Capulli et al., 2017), or boldly seeking to engineer myocardial tissues that elicit the unique mechanical, biological, and electrical properties existing at cell-tissue interfaces throughout the heart (Kaiser & Coulombe, 2015).

For you formed my inward parts; you knitted me together in my mother’s womb. I praise you, for I am fearfully and wonderfully made. Wonderful are your works; my soul knows it very well.

– Psalm 139:13,14 (ESV)

Can you imagine a career researching and developing tissue scaffolds that might even mimic nature – God’s great creation?

Christian scholarship extending into professional roles is sincerely needed in education and culture. Chemical engineering and bioengineering can be a promising career for those who like to study physiology, microbiology, and biochemistry. As a starting point, we encourage you to reach out to teachers at Christian colleges. Undergraduate studies that include anatomy and physiology, as well as kinesiology, can provide a firm basis for learning the practical implications of biology and chemistry. This foundation can lead to future studies in biomaterials and tissue engineering, including biomimetic applications, as graduate students.

References

Anderson, J.M. (2004). Inflammation, wound healing, and the foreign-body response. In Ratner, B., Hoffman, A., Schoen, F., & Lemons, J. (Eds.), Biomaterials science: An introduction to materials in medicine (2nd ed., pp. 296-303). San Diego, CA: Elsevier Academic Press.

Bell, E. (2000). Tissue engineering in perspective. In Lanza, R.P., Langer, R., & Vacanti, J. (Eds.), Principles of tissue engineering (2nd ed., pp. xxxv-xli). San Diego, CA: Academic Press.

Capulli, A.K., Emmert, M.Y., Pasqualini, F.S., Kehl, D., Caliskan, E., Lind, J.U., … Parker, K. (2017). JetValve: Rapid manufacturing of biohybrid scaffolds for biomimetic heart value replacement. Biomaterials, 133, 229-241. [View in article]

Chan, B.P., & Leong, K.W. (2008). Scaffolding in tissue engineering: General approaches and tissue-specific considerations. European Spine Journal, 17(supplement 4), 467-479. [View in article]

Gerhard, E.M., Wang, W., Li, C., Guo, J., Ozbolat, I.T., Rahn K.M., … Yang, J. (2017). Design strategies and applications of nacre-based biomaterials. Acta Biomaterialia, 54, 21-34. [View in article]

Green, D., Howard, D., Yang, X., Kelly, M., & Oreffo, R.O. (2003). Natural marine sponge fiber skeleton: a biomimetic scaffold for human osteoprogenitor cell attachment, growth, and differentiation. Tissue Engineering, 9(6), 1159-1166. [View in article]

Green, D.W., Lai, W., & Jung, H. (2014). Evolving marine biomimetics for regenerative dentistry. Marine Drugs, 12(5), 2877-2912. [View in article]

Kaiser, N.J., & Coulombe, K.L.K. (2015). Physiologically inspired cardiac scaffolds for tailored in vivo function and heart regeneration. Biomedical Materials, 10(3), 1-26. [View in article]

Kakisawa, H., & Sumitomo, T. (2011). The toughening mechanism of nacre and structural materials inspired by nacre. Science and Technology of Advanced Materials, 12(6), 1-14. [View in article]

Koh, T.J., & DiPietro, L.A. (2011). Inflammation and wound healing: The role of the macrophage. Expert Reviews in Molecular Medicine, 13(e23), 1-14. [View in article]

Luz, G.M., & Mano J.F. (2009). Biomimetic design of materials and biomaterials inspired by the structure of nacre. Philosophical Transactions of the Royal Society A, 367, 1587-1605. [View in article]

O’Brien, F.J. (2011). Biomaterials & scaffolds for tissue engineering. Materials Today, 14(3), 88-95. [View in article]

Ratner, B.D. (2001). Replacing and renewing: Synthetic materials, biomimetics, and tissue engineering in implant dentistry. Journal of Dental Education, 65(12), 1340-1347. [View in article]

Sled, E. (2018). Biblical integration in anatomy and physiology: A design approach. Answers Research Journal, 11, 141-148. [View in article]

Williams, D.F. (Ed.) (1999). The Williams dictionary of biomaterials. Liverpool, England: Liverpool University Press.

Wininger, K.L., Bester, M.L., & Deshpande, K.K. (2012). Spinal cord stimulation to treat postthoracotomy neuralgia: Non–small-cell cancer: A case report. Pain Management Nursing, 13(1), 52-59. [View in article]

Previous articles in this series:

The next installment in our biomimetic series focuses on cardiovascular medicine!

Our next installment will discuss biomimetic applications in cardiovascular medicine, including commentary on how much of the work in cardiac tissue engineering is focusing on regenerative medicine. However, with respect to regenerative medicine, we will try to center our discussion on methods that think outside-the-stem-cell box.

Biomimicry 101: Introduction to Biomimicry (and Biomimetic Applications)

kingfishersThe common or Eurasian kingfisher (depicted above on the left), and the belted kingfisher (depicted above on the right).
bullet-trainThe nose of Japan’s 500 series bullet train was fabricated to mimic the design inherent in the beak of a kingfisher to reduce drag and improve aerodynamics as the train exits tunnels.

Since the 1940’s, biomimicry has become increasingly commonplace as an integral approach to problem solving. The word biomimicry means to mimic life; the adjective form of the word is biomimetics.

— Biomimicry and the Bullet Train —

Biomimetic applications are becoming more widespread, and solutions to the problems they solve are growing more and more purposeful and specialized, with the array of applications varying, for instance, from medicine to industrial design and industrial engineering. One exceptional case in recent years involved Japan’s 500 series bullet trains. A design flaw surfaced when this series came online in the late 1990’s. The issue boiled down to the bullet-shaped, rounded-off nose designated for each lead car. It was anticipated that this shape would be highly aerodynamic, but the contours favored a rather unnerving pressure gradient. This pressure gradient, known as a shock or pressure wave, triggered a sonic boom every time a train exited tunnels at operating speeds. To remedy this problem, train architects took their cues from kingfishers.

A kingfisher is a type of bird ranging throughout many temperate and tropical climates. Often one or two may be seen perched above banks along rivers and fresh water ponds and lakes (see the images of two different species of kingfishers above). As the name suggests, they feed on fish. What is more, the kingfisher often conveys a stately, prominent mannerism, which lends itself towards being somewhat showy. You might say they have good stage presence. As master anglers, kingfishers dive headfirst into the water to catch their meals. They strike with skilled accuracy — starting from a perch or in a hovering position, and then plunging out of the sky beak-first into the water like a dart. Yet, even though their beaks pierce the water, breaking the water’s surface tension, kingfishers barely create a ripple.

It was this ability, the zeroing out of the point-of-entry pressure wave, which made a distinct impression on the 500 series’ architects. And it was inspiration resulting from that impression which ended up being the key to solving the problematic sonic boom dilemma. With the dynamics of the kingfisher in mind, the architects retooled the nose of the bullet train to mimic the inherent design in the kingfisher’s beak. Indeed, after completing their imaginative and inspired rhinoplasty, the trains’ newly engineered noses nullified the pressure gradient that had once plagued them in the original fabrication. Most importantly, the new, elongated profile did away with the sonic boom altogether.

The example of the bullet train gives us a clear picture of how biomimicry can capture the imagination and attention of industrial designers and mechanical engineers. The 500 series bullet trains operated from 1997 to 2010.

Remark: By all accounts, the species of kingfisher that train designers took notice of is the common or Eurasian kingfisher (depicted above on the left). The kingfisher common to North America is the belted kingfisher (depicted above on the right).

— The Original Hook and Loop Fasteners —

The original hook and loop fasteners (think VELCRO® brand fasteners) lend another historical perspective on biomimicry. Swiss engineer and inventor George de Mestral discovered these novel fasteners. The story says that when walking his dog through the Swiss countryside in the early 1940’s, de Mestral was intrigued with the burrs that stuck to its fur coat (as well as to de Mestral’s clothes). Upon closer inspection, de Mestral realized that the tips of the spikes of a burr have a unique design, a tiny hook. And while each burr contained dozens of spikes, in reality each burr contained dozens of miniscule hooks. What is more, de Mestral came up with a way to duplicate these naturally-occurring miniaturized hooks synthetically, and he combined them with fasteners containing hundreds of tiny loops. Today, VELCRO® brand fasteners continue to be a well-known application of biomimicry, as they are by far one of the most widespread, useful examples.

Remark: Please click here to learn more about the history of VELCRO® brand fasteners, including the fun fact that these fasteners accompanied Neil Armstrong during mankind’s first walk on the moon. (As a side note, readers who are interested in knowing more about Neil Armstrong may do so via our recent blog that celebrated the 49th anniversary of Armstrong’s first steps on the moon. In addition, readers will also find interesting tidbits comparing and contrasting evolutionary theories about the moon versus its creation.)

— Biomimetic Innovation —

Because biomimicry is such an innovative and unique field of study, we at Ashland Creation Colloquium are dedicating an entire series to the topic. We are calling the series Biomimicry 101. Our aim is to showcase creation. Creation is the biblical account of everything concerning our world and the universe (i.e., the who, what, when, where, and why – and perhaps even the how). At its core, creation takes into account “intelligent design” via a designer (i.e., creator). This designer is the God of the Bible.

Remark: Creation scientists carefully consider biblical perspectives when exploring, testing, and describing the richness of the universe. Given that scientists specialize in particular fields of study, creation scientists explore the universe through specific scientific disciplines encompassing the finite to the infinite, i.e., the life sciences to the field of cosmology.

For the balance of this article, we will clarify several key terms that lay a foundation for relevant and comparative studies instrumental to the field of biomimicry. Then, given this foundation, we outline topical categories that will be covered for the remainder of the series.

Key terms – the so-called “bio” group:

The intent of this section is to help differentiate between key terms, which collectively, we will refer to as the “bio” group. Individuals who work within this group are well-suited to explore and apply biomimicry.

Biomimicry, biomimetic(s), and bionic(s)

  • As defined above, the first two terms simply refer to mimicking life, with the first term being a noun and the second term the adjective form.
  • From the perspective of science and medicine, bionics may be thought of as the integration of that which is mechanical with that which is physiological (via a better understanding of the nervous system). The best example is functional electrical stimulation, which is a field that seeks to restore movement and automatic function, among other goals. Technology brought about by neural engineering is at the core of bionics, the leading edge of the neural interface.

Bioengineering

  • We can think of bioengineering as a broad category that focuses on medical applications. The field of regenerative medicine gives us a prime example. One specific area of research in regenerative medicine is the attempt to rectify impairments associated with the loss of normal spinal function. For example, attempts are ongoing to regenerate diseased vertebral discs, as well as damaged nerve cells (i.e., neurons) within the spinal cord.
  • Bioengineering may be defined within the broader category of biomedical engineering. However, because bioengineering focuses almost purely on innovations in healthcare and medicine, distinguishing between bioengineering and biomedical engineering can have practical advantages for clear communication.

Biomedical Engineering

  • As described above, biomedical engineering can serve as an umbrella term for bioengineering. The reason refers to the recognition of the term biomedical engineers by the U.S. Bureau of Labor Statistics to identify individuals who work in biomedical engineering. However, often the term biomedical engineer is used by individuals who service medical equipment, such as physical therapy equipment, operating room equipment, or heart monitors. In most regions across the country, you will find a biomedical engineering department housed in your local hospital, where the hospital staff may simply call the department “biomed.”

Bioneer versus Biomedical Engineer

  • The term bioneer is a recently introduced term which combines the words “biological” and “pioneer.” And although bioneer has not received a formal definition, it seems to be used in a colloquial sense to describe a person at the forefront of the biological sciences frontier.
  • In contrast to bioneer, the term biomedical engineer has been widely adopted. According to the website of the U.S. Bureau of Labor Statistics (click here), biomedical engineers are individuals who “combine engineering principles with medical and biological sciences to design and create equipment, devices, computer systems, and software used in healthcare.”
    • Field engineer is a term sometimes used within biomedical engineering. The term is mostly associated with biomedical engineers employed by the makers of highly specialized medical equipment, such as MRI and PET scanners. These individuals have gone through specialized training to travel in the field to handle more delicate service and repair requests.

Biostatistics

  • The discipline that integrates statistical analysis with the biological sciences is biostatistics. For example, a biostatistician may work with biologists, chemists, material scientists, chemical engineers, and industrial engineers to apply statistical methods that help solve real-world problems. Biostatisticians also provide analytical guidance for feasibility studies, preliminary research for investigational trials, and ongoing support for current research programs.

Biosensor(s)

  • Biosensors use biological agents and/or processes in the detection of other biological agents and/or processes. Microfluidic chips for the detection of malaria and a microelectromechanical system (often abbreviated MEMS) that detects Dengue virus are two such examples. These types of devices may be referred to as “lab-on-a-chip technology” or “point-of-care testing.” Yet biosensors also consist of specialized machinery for the detection of biological states and diseases (i.e., physiological abnormalities). Examples of these types of biosensors include molecular imaging scanners, such as magnetic resonance imaging (MRI), positron emission tomography (PET scans), and single-photon emission computed tomography (SPECT scans). In fact, researchers driving the new paradigm – the next frontier – in biosensing and diagnostic medical imaging are attempting to combine, or fuse, MRI and PET imaging techniques (so-called fusion imaging). Moreover, it was only recently that the fusion of PET and x-ray computed tomography (CT) held this distinguished honor as the new frontier.

Biomaterial(s)

  • Biomaterials are engineered materials placed into the body to minimize loss of structure and function. The material or object placed into the body is known as a foreign body. Based on our body’s reaction to such materials, there are three characterizations of the foreign body, as follows:
    • Intolerable
    • Tolerable
    • Biocompatible
      • The goal of biomaterial engineers is to achieve biocompatibility. To date, however, this goal has not yet truly been attained. Therefore, understanding normal tissue healing and foreign body response becomes critical to achieving biocompatibility.

Biomechanics (think Kinesiology)

  • The study of biomechanics is to better understand the mechanics of the body, and it includes human locomotion as well as body systems (such as the cardiovascular system). A biomechanics approach to locomotion first considers statics versus dynamics, and then considers kinetics and kinematics. We can say that kinetics examines the external forces acting on the body, and that kinematics describes movement without regard to such forces. Often the words biomechanics and kinesiology are used interchangeably. However, kinesiology means the study of movement, and it is more intently focused on anatomy and physiology, particularly the neuromusculoskeletal system.

The focus of this series seeks to relate the benefits of biomimicry on the humanities, and the topics that will be surveyed are as follows:

  • Biomaterials
  • Cardiovascular Medicine
  • Other Medical Applications
  • Biosensors
  • Turbulence and Chaos Theory
  • Insert: On Eagles Wings
  • Water Purification Systems
  • Human Gait: Biomechanics/Kinesiology
  • For More Information (and Education)
    • Here we feature a formal biomimicry fellowship sponsored through the University of Akron’s Integrated Bioscience PhD Program, and similarly highlight the Great Lakes Biomimicry Institute.

When you find yourself pondering just what biomimicry is, think design, intelligent design, and creation, but please don’t think evolution. And then when considering biomimetic applications, let your imagination know no bounds.

The next installment in our biomimetic series will deal with biomaterials!