Thin body parts like these are the easiest to design. Thicker organs, such as hearts and livers, require a stronger frame. For that, a lattice of sugar—like the haute cuisine sugar cages some chefs confect for desserts—is often used to provide a firm scaffolding, and then cells are layered over it. Sugar is nontoxic and melts in water, so when the organ is finished, the sugar scaffold is rinsed away, leaving hollow vessels for blood flow where they’re needed. The goal isn’t to create an exact replica of a human heart, lung, or kidney—which after all took millions of years to evolve—nor does it need to be. A kidney cleans the toxins from the blood, but it doesn’t have to look like a kidney bean or a kidney-shaped swimming pool. So it could become body art, a sort of interior tattoo: a heart-shaped kidney for a romantic, a football-shaped one for a sports fan. Or would that alter the brain’s mental atlas of the body, a landscape we know by heart, even in the dark? Suppose you have a suitcase. You replace the handle, you replace the lock, you replace the panels. Is it the same suitcase? If we replace enough body parts, or don’t choose exact replicas, will our brain still recognize us as the same self?
THE (3D-PRINTED) EAR
HE LENDS ME
L
awrence Bonassar’s lab in Cornell University’s Weill Hall sits across the street from a jewel of a tiny flower garden, now blanketed in snow. Though Weill’s outside walls are white as the season, it’s one of the “greenest” buildings in the country, which has earned a rare gold LEED rating, thanks to everything from recycled building debris and materials (such as the outer skin’s white aluminum panels) to a cooling roof planted with succulents and flowers, heat-reflective sidewalks, a giant atrium with passive solar heat, and motion sensors that turn on lights, temperature, and air flow only as needed, when people appear.
Opened five years ago, as a state-of-the-art home for the Department of Life Sciences, it’s been designed as an intellectual crucible with large overlapping labs. Long open sunlit rooms, running the length of each floor, share common lounges, corridors, and microscope areas, making it impossible
not
to bump into postdocs in related fields. Even in winter, cross-pollination is encouraged. Just as the planners hoped, many collaborations have ensued, the new
field of regenerative medicine is taking wing, and bioprintmakers are crafting tailor-made body parts.
The principle of “regenerative medicine” is magically simple: if a heart or jaw is damaged, either teach the body to regrow another or print a healthy new one the body will embrace. What Bonassar’s lab regenerates is the body’s vital infrastructure of cartilage: all those cushions (the so-called disks) between the vertebrae in the spine; the easily torn meniscus in the knee; the accordion of semicircular rings that keeps the trachea from collapsing when we breathe, yet allows it to bend forward when we swallow; the external ear, prized by poets and nibblesome lovers, who often describe it as “shell-like.” His goal is to restore lost function to ragged physiques and fix facial defects. To that end, he mingles tools from several disciplines, including biomechanics, biomaterials, cell biology, medicine, biochemistry, robotics, and 3D printing. If your only tool is a ruler, you’ll tend to draw boxes. New tools create new mental playgrounds. On this playground, spare ears abound.
What could you do with a spare ear? If a patient with skin cancer has to have an ear removed, the traditional way to replace it is with a prosthetic, but that has to be donned every day. A young mother in exactly that fix lamented to CBS News, “I could just see my kids running around with it, yelling ‘I have mommy’s ear!’” Instead, surgeons at Johns Hopkins harvested cartilage from her ribs, shaped it into an ear, and implanted it under her forearm skin, where it could be nourished by her own blood vessels. Just four months later, when the ear had grown its own skin, it was removed from her arm and attached to her head. Yet, wonderful as her new homegrown ear was, the process required numerous operations, including breaking open the vault of the chest and stripping cartilage from the ribs, then shaving and shaping the ear to fit. A feat of
subtractive
manufacturing.
Or an ear might rescue the one child out of nine thousand who is born with microtia, a condition in which the external ear hasn’t fully developed, sometimes leaving only a small peanut-shaped vestige behind for classmates to ogle and mock. A father of three young
children—twin six-year-old girls and a five-year-old boy—Bonassar is deeply sympathetic to the condition, and mindful of what early fixes can mean. Unfortunately, children aren’t able to brave an operation like the young mother’s until they’re six to ten years old, because they don’t have enough rib cartilage. Also, the operation is very painful and quite traumatic, and you don’t really want to subject a child to it. How much simpler, less invasive, and cheaper to do an MRI, CT scan, or 3D photograph, then print the cartilage out on demand in the exact shape of each child’s highly personal ear. You’d be able to do it much earlier in a child’s life, and you could photograph the left ear, flip it around to make a right ear, and match the geometry perfectly.
Microtia doesn’t harm hearing, but it often invites the social nightmares of bullying and shunning, just as a child is detailing a sense of self. So, although a new ear is only a cosmetic change, it has an enormous impact on a child’s hope of making friends—which in turn shapes a growing child’s brain. The ability to smile is a child’s coin of the realm, pleasant ears and face its passport. As I learned volunteering for a short spell with Interplast in Central America, the sooner you can repair a harelip, birthmark, or other deformity, the better chance a child has to bond with her parents, let alone strangers.
I don’t really need a new ear. Except for the occasional snare-drum of tinnitus or missed stage whispers, mine are working passably well. And the outer shells fit the size of my head. I could use more cartilage in my left knee, and a new spinal disk one day, but I don’t fancy today’s remedies—a cold metal implant, or a gift from a four-legged animal.
Nonetheless, a homegrown ear is what Lawrence Bonassar offers me, extending it in his open hand, as if it were sprouting out of his palm and shaking hands were just another form of listening. Translucent white, the ear feels smooth and warm as amber, and my thumb automatically plays over its many ridges and folds. I’m surprised by the level of minute detail. It’s quite odd to fondle a disembodied ear. Or a prizewinning one, for that matter. His bioprinting has won first
place in the World Technology Awards in Health and Medicine, the Oscars of the technology world, which celebrate inventions “of the greatest likely long-term significance for the twenty-first century.”
The ear he lends me is solid, yet bendy as a dried apricot, and would flex easily under the skin. But this one isn’t intended for anyone’s head. He returns it to a glass jar of preservative and sets it back on a shelf. His lab looks like the mental crossroads it is: a chemistry lab full of microscopes, workbenches, sinks, glass, and stainless steel. But also a medical facility, complete with large incubators, sterile fields, and countless drawers of parts and molds. And also a tech center equipped with computers, robots, and of course 3D printers. All accompanied by a seemingly endless wall of windows.
Outside there is the frail enchantment of snow, and a school bus creeping by like the orange pupa of some colorful butterfly.
One long ray of sunlight like a pointing finger touches a white desktop box about the size of the first manual typewriter, but less complicated looking. Two steel syringes with nozzles float above a metal warming plate, where they’ll begin hope’s calligraphy. The ink may be living cells of any type, life’s pageant in a polymer. When the nineteenth-century painter Georges Seurat used a similar stipple technique with pure color, his dots seemed to blend, but that was merely sleight of eye. These dots merge because cells fuse freely; they don’t need a human nudge.
As the moving pen writes, it doubles back over each line, stippling new layers, until it creates an outer ear that isn’t exactly organic in the way a wart or an eyelash is. Still, when transplanted, it will twitch with life, feel embodied, and help redefine what we mean by “natural.” Then any tangle of flesh and blood will serve as home, making rejection obsolete. For once in our long-storied evolution, a body part isn’t molded solely by evolution’s blueprint—we can choose its design. And forget years. Once he receives the MRI, CT, or 3D image, Bonassar can grow an ear in fifteen minutes. The time it takes me to walk to my local coffee shop.
Bonassar has mastered the art of training materials to carry cells
and deposit them like puppies exactly where he wants while keeping them alive and happy. And, just like healthy pups, the cells are agile enough to tussle without smooshing, hale enough to tug, eager to curve their tiny mouths inward and eat all the nutrients they need.
The two polymers he prefers are collagen—protein fibers the body uses as gluey twine and mortar—and alginate, a gel found in the brown seaweed I held at Thimble Islands, and used by drive-ins to make milk shakes thick and creamy as they swirl out of the dispenser. My parents had one of the first McDonald’s, where I sometimes poured shakes, and I know the consistency well—between syrup and toothpaste. That’s also the way bioprinters dispense ink, except that the carrier has clusters of living cells embedded in it.
When I ask Bonassar if he makes the scaffolds here, too, a proud smile appears, as he explains that the scaffolding
is
the liquid. This shake contains its own framework, so that an ear fresh from the printer is ready to go. And the ink? Water droplets wouldn’t stick together. Hard marbles would roll off. Instead he uses squishy collagen marbles, which cling to their neighbors. Like eggs or blood, collagen gels when it’s heated and the fibers scramble together. So he stores it cold, allowing it to stiffen only when it falls onto the warming plate.
It’s a technology he hijacked from Hod Lipson, and he began printing in Lipson’s lab with a printer wide as a brick hearth and heavy as an iron cauldron. Now it’s the size of an espresso machine and shockingly simple: load whatever you want into your syringe, place it so that the motor can grab the plunger and print, then adjust the rate ink squeezes out, and set the print head’s path. After that, two more steps remain.
He leads me through an open doorway into a tiny room packed with large machines, including a sterile culture hood with a large window, in which the whole bioprinter can be placed, safe from dust, fungi, and bacteria. It looks like an incubator for preemies.
“No,
this
is the incubator,” he says, turning to peer through a glass door into dimly lit shelves. “Look there. Can you see them?”
Rising on tiptoes, I see two petri dishes holding small strange buttons or perhaps tires. The odd items are spinal implants destined for a bouncing, braying fluff of a dog. Canine arthritis is a big problem for frolicsome dachshunds, hounds, and especially beagles—dogs with short necks and long bodies wear out their cervical disks and develop joint pains just as we do. Working with Cornell’s Veterinary School, Bonassar’s lab created implants with a gel-like core that pushes against a tougher outside ring, pressurizing it very much like blowing up a tire. It’s also a true organ, two different kinds of tissue that work together seamlessly.
In osteoarthritis, cartilage’s cushion wears out like an old pillow, and bone rubs bone raw, producing inflammation and pain. Almost everyone has a creaky-jointed sufferer in the family. Today’s back operations usually remove a damaged disk and fuse the vertebrae together with a metal plate, which creates the rigidity of a poker up the spine, doesn’t always work, and can make adjoining vertebrae weak as loose teeth. An alternative to fusion would be a godsend to sixty or seventy million people in the United States alone. Starting small, Bonassar replaced spinal cartilage in rats with his own lab-grown variety, and the rats lived normal lives, apparently pain-free. Next in line are larger animals—a dog, sheep, or goat—and if that works, then human volunteers will follow.
Bending to examine a smaller chamber alongside the incubator, I spot the next stage in the life of bespoke disks. Since all tissues in the body are weight-bearing and thrive under stress, his lab toughens the tissues, squeezing the implants over and over, as if they were pumping iron. This also quickens their metabolism, squooshing food in and smooshing waste out, making it more efficient. Such bioprinted implants could last longer than natural ones.
“It’s quite realistic to assume,” Bonassar says, hazel eyes sparkling, “that the first stages of the human clinical trials could happen within the next five years.”
When I ask about printing out hearts, lungs, and livers, he leads me to a large computer screen where he summons up a pair of
gloved hands holding what look like pieces of sushi: thick white slices with a thin halo of pink. A closer look reveals a rarer delicacy: ear implants fabricated from 3D photographs of Bonassar’s daughters’ ears. He smiles at them with a love pure as starlight. Then he points out the blood vessels in the thin rind around the implants, and the thicker comma of white tissue that’s quite bare. Yet those bare cells prosper, too.
The challenge with organs isn’t their size, it’s the plumbing. The bigger organs are like Venetian cities, fed by elaborate water streets afloat with gondolas. Many labs around the world are hunting the best ways to mirror those supply lines, and the elusive “aha moment” could be one week away or ten years. But its scent is in the air, and no one doubts it will soon revolutionize medicine with clean, healthy organs on demand. A touch of mental whiplash is to be expected.
It’s a hallmark of the Anthropocene that science and technology are galloping at such a pace that Bonassar’s field didn’t even exist when he was in high school or college. Now he’s among those ringing the biggest changes, including a dramatically new view of the human body and the jostles of cells that inhabit living tissues—even what a cell is and how a cell behaves. Not only do we know about stem cells, we’re starting to wield them in clever ways to mend the body, and it’s not arduous to do; it can be as simple as exposing cells to the right chemicals or stimuli. There’s been a stunning paradigm shift from the rule of
phenotype
—one cell type fated for one job and nothing else—to
phenotypic elasticity
, the idea that cells are far more versatile and can be repurposed, like a hammer used to anchor a kite.