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!