{"id":4498,"date":"2016-06-27T14:48:35","date_gmt":"2016-06-27T18:48:35","guid":{"rendered":"https:\/\/engineering.jhu.edu\/magazine-archive\/?p=4498"},"modified":"2016-07-22T14:48:46","modified_gmt":"2016-07-22T18:48:46","slug":"facing-the-future","status":"publish","type":"post","link":"https:\/\/engineering.jhu.edu\/magazine-archive\/2016\/06\/facing-the-future\/","title":{"rendered":"Facing the Future"},"content":{"rendered":"

By creating ready-to-implant plastic bone that can turn into living tissue, Warren Grayson and his team aim to improve life dramatically for patients undergoing facial reconstructive surgery<\/em>.<\/p><\/blockquote>\n

by<\/em> Douglas Birch<\/strong> photos by<\/em> Howard Korn<\/strong><\/p>\n

\"Warren<\/a>
Warren Grayson, associate professor in the Johns Hopkins Department of Biomedical Engineering,.<\/figcaption><\/figure>\n

Close your eyes and try to think of a friend or family member, says Warren Grayson. What do you see in your mind\u2019s eye? It\u2019s not likely to be his hair or her elbow. \u201cFor most people given that exercise, they\u2019re going to see the face,\u201d says the associate professor of biomedical engineering.<\/p>\n

Our face is integral to how other people see us and how we see ourselves. If it is disfigured by a genetic disorder, ravaged by cancer, or shattered in a car accident, the trauma goes much further than skin deep. \u201cOur facial bone determines our appearance; it determines our sense of self,\u201d says Grayson. And when the face is damaged or destroyed, he says, that \u201ccan damage our sense of self.\u201d<\/p>\n

For Warren Grayson<\/a>, who holds joint appointments at the Whiting School of Engineering and the School of Medicine, the best solution to rebuilding faces is to stimulate the body\u2019s own machinery to build new bone from scratch. But tissue engineering is a very young science. While researchers have grown heart, lung, liver, eye, and bone tissue outside the body, few of these materials are being used routinely in clinical treatments. \u201cA lot of research gets stuck at the bench level,\u201d Grayson says, in his lilting Trinidadian accent. \u201cThese experiments so far have had relatively little impact on patients.\u201d<\/p>\n

Grayson, who is a patent holder at EpiBone, one of the world\u2019s most closely watched biotech startups, came to the Whiting School of Engineering\u2019s top-ranked biomedical engineering program<\/a> in 2009 with the goal of applying his research to rebuilding faces. \u201cWe\u2019re going to revolutionize the way that these people are treated in the health care system,\u201d Grayson says, his velvet voice and modest manner belying his soaring ambition.<\/p>\n

Today, Grayson is spearheading a collaborative effort with Johns Hopkins surgeons and other engineers to create a new approach to craniofacial bone surgery using 3-D printing, cell signaling techniques, and a patient\u2019s own stem cells to create living, anatomically precise facial bones. The goal is to provide patients who come to Johns Hopkins for facial reconstructive surgery with a ready-to-implant plastic bone that will gradually dissolve as living tissue forms.<\/p>\n

Amir Dorafshar<\/a>, associate professor of plastic and reconstructive surgery at the School of Medicine and clinical co-director of Johns Hopkins\u2019 Face Transplant Program, is working with Grayson on the facial bone regeneration project. \u201cI tell Warren what the problems are that we\u2019re facing on a day-to-day basis,\u201d Dorafshar says. \u201cI show him the defects that we\u2019re trying to address. Together, we work on how we are going to reconstruct these patients.\u201d<\/p>\n

Surgeons perform more than 200,000 bone grafts for facial and skull reconstruction each year in the United States alone, at a cost of about $1 billion. And the demand has grown by more than 2.5 times over the past 16 years.<\/p>\n

\u201cThe ability to generate a three-dimensional bone that can actually form real bone in a patient and can become a real, live viable tissue without the necessity for taking bone from another place in the body is huge,\u201d Dorafshar says.<\/p>\n


\nThe key to reconstructing a face is restoring the underlying bone structure. Our facial bones largely determine our appearance, which is why forensic artists can build lifelike busts from nothing more than a skull.<\/p>\n

Today, surgeons who are trying to reconstruct the face generally rely on the materials at hand. To build the jaw, for example, they may harvest bones from elsewhere in a patient\u2019s body, often a fibula\u2014the thinner of two bones in the lower leg. They break the fibula into four pieces, chisel them to fit, and rearrange them to rebuild the jaw. While the approach is considered state-of-the-art, Grayson calls it a \u201cstopgap.\u201d<\/p>\n

\u201cIt\u2019s a little like MacGyver, right?\u201d the 40-year-old engineer says, over a cup of coffee at Balducci\u2019s Cafe in the Johns Hopkins Hospital\u2019s Sheikh Zayed Tower. He is referring to the fictional 1980s TV character who could make anything using only a Swiss Army Knife and whatever came to hand. \u201cThere are not a lot of good options for people who have had craniofacial deformities,\u201d Grayson concludes.<\/p>\n\"Warren<\/a>\n

As a postdoc at Columbia University, Grayson developed a process that for the first time grew a precisely shaped piece of human jaw bone outside the body. He did this by creating a machine-milled, jaw-shaped scaffold made of bone from cows\u2019 knees, coating it with human stem cells, and then incubating it in a small, boxy device called a bioreactor, which fed nutrients and oxygen to the stem cells while molding the fresh bone to the proper shape.<\/p>\n

His paper on the work created a lot of excitement among tissue engineers and was featured in The New York Times and Scientific American, and the biotech startup EpiBone was launched to commercialize this work. The small company was one of 49 worldwide invited to the 2016 World Economic Forum in Davos, Switzerland, in January.<\/p>\n

In the Biomedical Engineering Department, Grayson plans to speed up adoption of his approach to facial regeneration by streamlining the process. He hopes to eliminate the bioreactor and use 3-D printers to produce custom-designed, porous, biodegradable plastic scaffolds in the shape of the required bone that can be implanted directly in the face.<\/p>\n

The whole procedure might take just six to 12 hours, compared to the five weeks required to incubate new bone outside the body. And it would help the body start work immediately on absorbing, integrating, and replacing the implant.
\n
\n\"Warren<\/a>On a chilly day in late winter, Grayson sits in his fifth-floor office in the gleaming Robert H. and Clarice Smith Building on the East Baltimore campus, explaining his research. Photographs of two of his role models, President Barack Obama and the boxer Muhammad Ali, hang side by side on one wall.<\/p>\n

The slim, soft-spoken tissue engineer, the father of five school-age children, is married to Catherine Sewell, a gynecologist and medical officer at the Food and Drug Administration. He was born in Arima, a city of 33,000 on the island of Trinidad, where both his parents were teachers who rose to become high school principals. As a student, he says, he loved math, physics, and chemistry, and early on decided to become an engineer. Since most engineers in Trinidad and Tobago work in the oil and gas industry, that\u2019s where he assumed he would end up.<\/p>\n

But during soccer practice one day when he was earning his engineering degree at the University of the West Indies, the slim midfielder tried to cut between two defenders, planted his foot wrong, and tore the meniscus in his right knee.
\nA piece of cartilage lodged itself in the joint, making it impossible to bend his knee. An orthopedic surgeon studied the knee and leg muscles, twisted Grayson\u2019s ankle, and popped the torn meniscus out. \u201cAt the end of that session, I was able actually to walk out of the office,\u201d he says.<\/p>\n

It was a painful but inspiring demonstration, Grayson says, of how an injury could be treated as an engineering problem. \u201cWhat was enthralling was watching the doctor,\u201d he says. \u201cBeing able to see what a doctor does and how a doctor can impact a patient\u2019s life\u2014I think that was the part that stood out to me.\u201d<\/p>\n

After considering medical school, Grayson instead became the first doctoral student in the biomedical engineering program at Florida State University, where he focused on how 3-D environments and oxygen levels inside the body influence the development of mesenchymal stem cells, which hold the potential to differentiate into a variety of cell types, including bone, cartilage, and muscle cells.<\/p>\n

After earning his PhD, he completed his postdoctoral fellowship at Columbia under Gordana Vunjak-Novakovic, who says she was impressed by Grayson\u2019s maturity and ambition. His research focused on developing a bioreactor to help stem cells build an anatomically precise temporomandibular joint. The jaw\u2019s connection to the skull, it is crucial to chewing and speaking.<\/p>\n

While making bone tissue with stem cells is one thing, making it with a precise shape is another. \u201cHe really started from scratch,\u201d says Vunjak-Novakovic. \u201cBefore, we had the technology for engineering bone, but nothing like anatomical bone. This was never done before.\u201d<\/p>\n

When Johns Hopkins offered him a job in 2009, he jumped at the opportunity. His goal, he says, was to translate his research from the bench to the operating room, which he saw as Johns Hopkins\u2019 great strength. \u201cThat\u2019s a critical element that attracted me to come to Baltimore,\u201d he says. He adds, half-jokingly, that previously he had spent his career moving north from the equator\u2014from Trinidad to Florida to New York City. \u201cSo I was happy to come back toward the south,\u201d he says, smiling.
\n<\/p>\n

\"Alexandra<\/a>
Alexandra Rindone, a biomedical engineering graduate student, works in Grayson’s lab.<\/figcaption><\/figure>\n

Engineering a new face isn\u2019t like building a bridge or a skyscraper. Cell and tissue engineers work with softer, more dynamic materials in an environment\u2014the human body\u2014that is far more complicated than most building sites.<\/p>\n

\u201cWhether you\u2019re a civil engineer or a chemical engineer, there are set rules in those fields,\u201d Grayson says. \u201cYou know how fluids flow within pipes. You know how matter responds to forces, and so forth. Right? It\u2019s not the same thing in biology. From person to person, those rules may change. Within the same person in different parts of the body, the same material may respond differently.\u201d<\/p>\n

Researchers are approaching the problem of rebuilding facial bone from a number of angles. More than a decade ago, researchers in Germany soaked titanium mesh shaped like a piece of jawbone in stem cells and implanted it in the muscles of a patient\u2019s back to promote the growth of blood vessels.<\/p>\n

Several months later, surgeons removed a hybrid metal-tissue replacement jaw and re-implanted it in the patient\u2019s face. The procedure helped the patient eat his first solid meal in nine years. But titanium implants can cause inflammation, don\u2019t develop with the surrounding bone, may require periodic replacement that can cause infections, and leave multiple scars.<\/p>\n

With Grayson\u2019s approach, surgeons would scan a patient\u2019s face using CT and transmit the data to tissue engineers. Tissue engineers would use a 3-D printer to produce a porous, biodegradable plastic bone filled with chemical and equipped with physical and chemical signals\u2014such as specific textures, ground-up bone, and tiny beads designed to release precise levels of oxygen\u2014to direct stem cell growth.<\/p>\n

Within 12 to 24 hours, Grayson says, this plastic bone would arrive at the operating room in a sterile package. Surgeons would liposuction stem cells from the patient\u2019s own fatty tissues, to avoid rejection, and coat the artificial bone with them to start the process of regeneration.<\/p>\n

Gradually, the artificial jawbone would dissolve over six months to a year. \u201cThe entire implant degrades and is replaced by native host tissue, and you essentially have a jawbone that\u2019s your jawbone,\u201d says Ethan Nyberg, a PhD candidate in Grayson\u2019s lab.<\/p>\n

Persuading stem cells to make the kind of tissue required in just the right shape and at just the right time is tricky. In deciding what kind of tissue to become, stem cells respond to subtle environmental and chemical signals, such as oxygen and calcium levels. Higher oxygen encourages bone growth, while lower oxygen can trigger the development of blood vessels. Both are needed to build a new bone.<\/p>\n

There are also regulatory hurdles. So far, the FDA has not approved any stem cell-based products for use, other than blood-forming stem cells harvested from the umbilical cord. But Grayson believes the challenges can be surmounted.<\/p>\n

Nyberg sits at a bench papered with sticky notes bearing inspirational messages, including \u201cAn idea without execution is a delusion.\u201d He is working on signaling stem cells to create blood vessels. He\u2019s also helping test a new 3-D printer in the lab, which will be used to produce the scaffolds for the implants. A clear plastic box by the printer holds some of the first products: ears made of plastic mesh and a tiny, perfectly formed, red plastic skull.
\n
\n\"Warren<\/a><\/p>\n

Ashley Farris, a first-year PhD student in Grayson\u2019s lab, is trying to develop a method for delivering oxygen to stem cells as they populate and replace the plastic bone scaffold. Her work is made possible through funding Grayson received from the university; he was recently selected as one of 37 early-career researchers from across the university system to receive a Catalyst Award of up to $75,000 to help them kick-start their work.<\/p>\n

Farris\u2019 plan is to use plastic beads\u2014the size of baking soda crystals\u2014filled with oxygen under pressure that slowly release the gas over weeks or months.<\/p>\n

To produce a precisely calibrated oxygen level, the beads\u2014called microtanks\u2014will be embedded in the scaffold during the 3-D printing process. Farris says her toughest task is designing the slow-release polymer shell for the tanks, but she is optimistic about the work.<\/p>\n

She says she was attracted to the world of tissue engineering because it\u2019s at the interface of many different fields. \u201cYou have materials scientists, clinicians, chemists, and biologists all working together to solve the same problem,\u201d she says.<\/p>\n

Whiting School Dean Ed Schlesinger says that Grayson\u2019s work, which holds the promise of changing lives in \u201cdramatic and immediate ways,\u201d could only be done at a school like Johns Hopkins, where the skills of researchers from so many different fields can be applied to medicine.<\/p>\n

\u201cIf you think about the work he\u2019s doing, it is materials engineering to develop the scaffolding materials,\u201d Schlesinger says. \u201cIt\u2019s biology and chemical engineering to encourage the growth of the tissues that have to replace that artificial scaffolding. It\u2019s imaging and computer science to design the prostheses. It\u2019s the surgery and the medicine that\u2019s involved in the actual deployment of these prostheses. It\u2019s the communications with the surgeons and with the physicians to understand what the issues are and what needs to be done. If you really think about all the aspects, it is remarkable.\u201d<\/p>\n

To provide the infrastructure for this approach, Grayson is in discussion with colleagues about creating an institute for craniofacial reconstruction, which would include a 3-D printing facility and other labs for preparing facial bone implants for surgery.<\/p>\n

As Grayson tries to orchestrate the science and funding for his vision, he says he tries not to lose sight of the ultimate goal. Every day, he says, he and his research team \u201cnever forget why we do the research.\u201d<\/p>\n

\u201cThis is going to revolutionize [life for] cancer patients, trauma victims, soldiers coming back from wars, accident victims, or even children with missing bones,\u201d Grayson says. \u201cWe are going to change the face of medicine.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"

By creating ready-to-implant plastic bone that can turn into living tissue, Warren Grayson and his team aim to improve life dramatically for patients undergoing facial reconstructive surgery. by Douglas Birch photos by Howard Korn Close your eyes and try to think of a friend or family member, says Warren Grayson. What do you see in…<\/p>\n","protected":false},"author":4,"featured_media":4614,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[28],"tags":[121,285,286,287],"class_list":["post-4498","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-features","tag-department-of-biomedical-engineering","tag-warren-grayson","tag-johns-hopkins-face-transplant-program","tag-craniofacial-bone-surgery","issue-summer-2016"],"acf":[],"yoast_head":"\nFacing the Future - JHU Engineering Magazine<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/engineering.jhu.edu\/magazine-archive\/2016\/06\/facing-the-future\/\" \/>\n<link rel=\"next\" href=\"https:\/\/engineering.jhu.edu\/magazine-archive\/2016\/06\/facing-the-future\/2\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Facing the Future - JHU Engineering Magazine\" \/>\n<meta property=\"og:description\" content=\"By creating ready-to-implant plastic bone that can turn into living tissue, Warren Grayson and his team aim to improve life dramatically for patients undergoing facial reconstructive surgery. by Douglas Birch photos by Howard Korn Close your eyes and try to think of a friend or family member, says Warren Grayson. 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