Biomedical Biomimicry

Bio-Inspired  Biomedical Research by Dr. Knothe Tate

By Marianne Eppig on assignment for E4S

We survive because nature has provided us with nearly perfect living machines—our bodies.  Its mechanisms allow us to procreate, heal, and regenerate cells; take any part of the body and there is some lesson to be learned.  Think of bones: how do they build strength, adapt, and stay strong?  Melissa Knothe Tate, Ph.D. has spent her career answering these questions by studying bone activity, which has in turn inspired her to create technology that might actually exceed Mother Nature’s capabilities.

Inspired by nature’s abilities and failures in terms of health and aging, Dr. Knothe Tate considers her work in biomedical engineering to be biomimicry, or “bio-inspired.”  A professor and researcher at Case Western Reserve University, Dr. Knothe Tate defines biomimicry as replicating a biological model or process to achieve a desired property, characteristic, or mechanism.  

Both fascinated and inspired by nature’s genius and motivated to improve upon some of its imperfections in survival techniques, Dr. Knothe Tate attests that she and her team are “not just mimicking nature; we’re being inspired and taking it a step further, I hope.”

The desire to beat nature may seem vain or at the very least impossible, but Dr. Knothe Tate’s intention is nothing if not benevolent.  She hopes to find medical solutions to bone and tissue deterioration due to age or disease.  In doing so, she is working on developing new technology that can approach nature’s mechanisms to promote survival, and then potentially exceed those capabilities.  To be able to create such technology, Dr. Knothe Tate and her team of researchers must study nature’s intricate designs and processes.

From Bones to Bandages
Imagine a bandage that could wick moisture away from a wound, while delivering antibiotics to heal it.  Dr. Knothe Tate has created such a bandage, among other incredible inventions, through her research of bone fluid dynamics.

To reach a better understanding of how fluids move within bones, Dr. Knothe Tate and her team built computer models of virtual bones.  They use computer models to study the flow of bone fluids because actual bones are both opaque and brittle.  For this very reason, the fluid dynamics of bones had never before been researched experimentally.  With computer models displaying the physical processes and the mechanical properties of bones, Dr. Knothe Tate and her team could see what happens within the bone when they alter specific bone variables.  By seeing how the bone reacts to changes, the scientists could significantly increase their knowledge of the biological system of bones.

From her bone research, Dr. Knothe Tate patented a technology that replicates the bone’s ability to imbibe fluid when pressed.  Since bones are both stiff and permeable (liquid can pass through the various holes and tunnels within them), bones can actually intake fluid when they receive pressure.

Dr. Knothe Tate has mimicked this ability in bandages that can pull fluid away from the wound, while simultaneously delivering pharmaceuticals, such as antibiotics, to the wound.  The wound dressings are currently in the process of being patented.  Along similar lines, this technology has been used to develop bed dressings that prevent bedsores by keeping moisture away from the body, patches that deliver medication through the skin, diapers that suck fluid away from children’s skin when they sit down, and moisture-wicking clothing and socks.

Strengthening Bones
A normal amount of healthy activity and exercise will actually produce a small amount of damage within bones, causing them to re-build themselves on a regular basis.  This constant re-building strengthens bones.

Astronauts, however, cannot naturally strengthen their bones in a gravity-free environment.  Dr. Knothe Tate discovered that she could use a lithotripsy device to deliver sound waves (which produce minor shock waves) in the body to artificially strengthen bones.  These small shock waves produce the amount of micro-damage necessary to trigger bones to re-build themselves, preventing bone loss for people who cannot get the amount of exercise their bones need.

Healing Critical Size Defects
With a broken bone, if a large enough piece of the bone is missing, it will be unable to heal on its own.  Melissa and her husband, Dr. Ulf Knothe, are trying to find a method to heal these breaks, called critical size defects.  Mimicking nature’s engineering strategy of stem cells might provide the solution.

The current method used by surgeons is called distraction osteogenesis and uses a metal ring around the outside of the leg with wires that go into the leg to move the bone back together a couple millimeters per day.  This is obviously a painful process that can cause scarring and infections.  Dr. Ulf Knothe is working on a method of using the sleeve on the outside of the bone—called the periosteum—where many stem cells reside, and pulling a section of it down over the critical size defect.  The section of bone where the periosteum came from can heal itself, and the stem cells from periosteum completely fill the cavity of the critical size defect with bone!  This method, according to Dr. Knothe Tate, “could really change the way doctors heal bones.”

Tissue Regeneration
Inspired by nature’s process of self-assembly, Dr. Knothe Tate is researching tissues with the intention of ultimately being able to replace or regenerate tissues that fail.  She commented, “No one builds tissue better than nature.”  Dr. Knothe Tate hopes to somehow use nature’s building paradigms to create biomaterials that can mend themselves, or adjust themselves, to better function in different biological environments.  “I think that’s the future of materials development,” she said.  By attempting to mimic the natural process of tissue construction, Dr. Knothe Tate is working on reversing natural degenerative processes.  

Learning from Stem Cells
Stem cells are the first signs of life, and they are responsible for constructing entire living beings from initially miniscule materials.  Stem cells are one of nature’s most amazing commodities.  

Dr. Knothe Tate says that her most empowering discovery of the last year has been learning from stem cells that have not yet been assigned to what they will become—a stage at which they are called uncommitted stem cells.  Within the first week after a baby is conceived, the stem cells of what will become the human being are incredibly sensitive to any signals within the mother’s womb.  Dr. Knothe Tate and her team discovered that stem cells at this stage are 1,000 times more sensitive to physical signals than cells in an adult’s cartilage.  

When the very first step in bone development begins, the stem cells are proliferating, colliding against each other, and starting to condense in utero.  As the cells come together, tissues are built and the cells specialize to enhance their own survival in response to spatial and temporal signals in their environment.  Dr. Knothe Tate and her team of researchers study the stem cell response by exposing them to various environmental signals.  

When exposed to the signals, the stem cells secrete structural proteins to buffer themselves against the signal and protect themselves from the environment.  Dr. Knothe Tate commented, “It’s incredible to think that at the level of a single cell, they can do that.  We’re doing a lot of work now to understand that and to watch it as it happens.”  Dr. Knothe Tate and her team believe that once they can define the environment of a stem cell and send it the correct signal, they can trigger the stem cell to build bone tissue.

In addition to her research, Dr. Knothe Tate is writing a book, titled Exploiting Nature’s Engineering Paradigms to Build Tissues and Materials, about her discoveries in stem cell research.

Passing on a Passion for Biomimicry
According to Dr. Knothe Tate, the ultimate purpose of her various realms of bio-inspired research is to improve the quality of life for humanity.  From her research on bones, tissues and stem cells, the medical sector and patients the world over will surely benefit.  Despite the international renown that Dr. Knothe Tate has gained for her research, she said that, “Probably my greatest contribution, beyond any discoveries that I make, is inspiring new generations to think outside the box.”  

Instead of asking her students at Case Western Reserve University to memorize equations or approaches, she challenges them to think analytically and to apply what they learn from nature to their work.  She said, “If I’m not in the lab using biomimicry, I’m in the classroom, trying to share the joy of this kind of innovation with them.”