THREE-DIMENSIONAL BIOLOGICAL PRINTING OF BONE...

IS THAT POSSIBLE?

"Fractured," has been out for about a year now and since then I've spoken at a number of author events. Invariably someone asks, "Is the science you talk about in the book real?" People want to know if it's possible to "print up" a bone. It seems too fantastic, like something Dr. McCoy would do on an episode of Star Trek. I hope to convince you it's not.

Recall that in the story the two main characters, orthopedic surgeon Mark Thurman and stem cell scientist, Claire Hodgson have discovered a method to make fractured bones heal super fast. We're talking days instead of months. To accomplish this feat they combine several strategies: stem cell manipulation, three-dimensional biological tissue printing (3D bioprinting), and drug therapy. I'll leave the discussion of anabolic drugs for another post and confine our discussion to the first two topics.

So, back to the original question, is this possible? Can we print up bones and make fractures heal over a weekend? Short answer: not quite yet but, we're close. Real progress is being made. Recently, scientists at Johns Hopkins University announced they had discovered a method to drive stem cells to form new bone. Stem cells are regenerative cells. They have the potential to develop into a variety of cells that make up the tissues of our body.

The Johns Hopkins scientists have created bone producing cells by genetically altering the stem cells to produced more of a protein called WISP-1. Cells with this alteration produced bone tissue in culture. When they blocked the production of WISP-1 the stem cells developed into fat producing cells. Then they tried it in bone-fusion experiments (where the goal is to make two or more bones to heal into one solid bone mass). In experimental subjects treated with stem cells containing an elevated amount of WISP-1 the bones fused. Subjects with decreased WISP-1 didn't fuse. They concluded the cell signaling protein WISP-1 controls gene expression causing stem cells to turn into a bone-producing cell, an osteocyte. In earlier work, researchers at the Hospital for Joint Diseases in New York City reported that another family of cell-signaling molecules, Wnt proteins, could cause similar effects in stem cells. So this technology is real, it's not science fiction; progress is being made in the ability to make stem cells preferentially turn into bone producing cells. Unfortunately we can't do it as well as Dr. Hodgson can, yet.

So it looks like we've got part of the problem solved. We can get stem cells to turn into bone producing cells, but can the bone scaffolding be made in a laboratory? You know, the hard stuff. Can they "print up" a bone? There are a number of laboratories working on this problem. In the book I refer to the Wake Forest Institute for Regenerative Medicine. WFIRM has been doing this type of work for a number of years and continues to perform cutting-edge research. However, last week exciting news came from another institution. Scientists from the Penn State College of Medicine and Penn State Biomedical Engineering Department published a paper in the Journal of the American Academy of Orthopedic Surgery about the current state of 3D bioprinting of bone and cartilage.

The authors point out that while notable shortcomings currently exist in available options for reconstruction of bone and articular cartilage defects solutions are on the horizon. They state "three-dimensional printing incorporating viable cells and extracellular matrix, 3D bioprinting, is an additive manufacturing tissue engineering technique that can be used for layer-by-layer fabrication of highly complex tissues such as bone and cartilage." Additive manufacturing refers to manufacturing by adding material to build the desired product. This is in contrast to subtractive manufacturing where material is cut away from a larger block until the desired shape is created. Think of a mason laying bricks to create a building (additive manufacturing) versus a sculpture chipping away at a block of granite to make a statue (subtractive manufacturing). Any type of 3D printing is additive manufacturing.

The researchers from Penn State report successful creation of composite tissues, including vascularized bone, using 3D bioprinting. They go on to say that "as this technology evolves, and we are able to integrate high-quality radiographic imaging, computer-assisted design, computer assisted manufacturing, with real-time 3D bioprinting and ultimately in situ surgical printing, this additive manufacturing technique can be used to reconstruct both bone and articular cartilage and has the potential to succeed where our currently available clinical technologies and tissue manufacturing strategies fail." Thus, at this time scientists are beginning to be able to use 3D bioprinting methods to make bone in the laboratory, but they have a ways to go. They can’t do it as well as Mark and Claire.

In "Fractured" Mark and Claire are able to combine these technologies. They use 3D bioprinters to make bone with stem cells placed within the bone structure. Once the printed bone is implanted in a patient the stem cells are stimulated to differentiate into bone producing cells. When this happens a fractured bone treated with this material heals much faster than expected, literally in days. There are a lot of obvious applications for this marvelous technology but there are some you might not think of off the top of your head, such as, horses.

Wait, what? Horses?

What do horses have to do with stem cells and 3D bone bioprinting? This technology could save a lot of injured horses. Believe it or not, today, in the twenty-first century, when a horse breaks a leg it must be euthanized. There are a number of reasons for this that I won’t go into now (that’s another whole blog post). Unfortunately, a fractured limb in a horse is a mortal injury. How big of a problem is this? It's a big problem, big enough to warrant articles in the New York Times, CNN, NPR last week. Let me pose a few questions to you. What if the three-year-old Thoroughbred favored to win the Kentucky Derby broke one of its limbs in a qualifying race? What if the owners were willing to pay anything to save him? What if an experimental new drug needed to make the process work is stolen and the scientist who discovered it vanishes? If this peaks your interest then look for "Hyperion's Fracture." It'll be available soon. Be sure to sign up for my email list at https://www.thomaskelso.com for upcoming information about the new book. Here's a sneak peak at the cover: