The concept of 3-D printing has become ubiquitous. Numerous retail stores such as Best Buy, Home Depot and Wal-Mart offer a glimpse of these little magical boxes whirring away, building cool tchotchkes. According to a market research company called CONTEXT, over half a million 3-D printers were shipped globally between the 1980s and mid-2015, with the millionth unit on track to ship by 2017. Early 3-D printers, used to build prototypes for industrial use, were expensive and specialized. But in the mid to late 2000s, key patents expired, allowing the low-cost personal/desktop 3-D printer market to expand. In fact, CONTEXT states that 85 percent of the half-million 3-D printers shipped to date fall into this personal/desktop market.
But 3-D printers are for more than just tchotchkes, and their impact in the medical field is beginning to take impressive shape. In 2015, the term bioprinting was officially added to the Oxford English Dictionary, defined as “The use of 3-D printing technology with materials that incorporate viable living cells, e.g. to produce tissue for reconstructive surgery.” Despite the official definition, the term is often used to reflect the use of traditional 3-D printers for medical applications. Indeed, most market research on 3-D bioprinters includes applications beyond tissue engineering. For example, there are more than 10 million 3-D printed hearing aids in circulation worldwide, and 3-D printing has become commonplace in dentistry, where it’s used in dental implants, crowns, veneers, orthodontic devices and more. Smartech predicts the market for 3-D printed dental products will reach $3.1B by 2020. (This does not include sales of the printers, themselves, which they forecast to reach $480M in the same timeframe.) These two industries are examples of the major role 3-D printing can play in improving patients’ quality of life, but the technology has had — and will continue to have — an even bigger impact in surgery and surgical preparation.
Many of today’s surgeries are complicated but, using CT scans and 3-D printers, surgeons can create an exact replica of what a tumor might look like on a kidney, or they can look inside a diseased heart to pinpoint the location and the extent of the damage they need to repair – before they open up a patient!
In 2014, 3-D printing proved vital in the preparation stages of a life saving surgery, as a five-year-old boy from Barcelona, Marc, faced a tumor that would be risky to remove. Marc had been diagnosed with a neuroblastoma, a common form of pediatric cancer that is normally relatively simple to remove. However, due to the network of blood vessels and arteries surrounding Marc’s growth, doctors at Hospital Sant Joan de Déu de Esplugues de Llobregat feared causing damage to his liver, kidney and stomach. After two failed attempts to operate on young Marc, the team spent ten days practicing on a 3-D-printed model before finally performing a two-part surgery and successfully removing the tumor.
Despite growing enthusiasm for the use of 3-D printing in surgical planning and medical training, cost is a significant obstacle. “The disadvantages are that it’s not covered by insurance yet, the software is expensive, you need a lab and you need a strong collaboration between the surgical and radiology departments,” Dr. Frank Rybicki, a radiologist and the director of the Applied Imaging Science Laboratory at Brigham & Women’s Hospital, told Modern Healthcare in 2014.
What about actual bioprinting with living cells? Combining the two emerging fields of tissue engineering and 3-D bioprinting will allow for custom building of bone, cartilage and skin for transplantation. In fact, development of thin non-vascular (without blood vessels) tissue such as cartilage and skin is well under way, with clinical trials in this space anticipated in the next two to five years.
But thick tissues, such as liver and kidneys, present the challenge of needing vasculature to supply nutrients, via blood, to keep grafts alive. To build artificial organs, eliminating the need for donors, is often referred to as the “holy grail” of both bioprinting and tissue engineering. According to the American Transplant Foundation, more than 123,000 people in the United States are currently on the waiting list for a lifesaving organ transplant. Another name is added to the national transplant waiting list every 12 minutes. On average, 21 people die every day from the lack of available organs for transplant. Plenty of research is underway in this space, but a solution is expected to take decades.
There is, however, a compelling use of bioprinted tissues in the process of drug discovery that will have a dramatic impact on medicine in a much shorter timeframe. The cost of bringing a new prescription drug to market is exorbitant, with estimates ranging from $2.5 billion to $5 billion. Enter 3-D printed tissue constructs, which should more closely mimic human tissue and provide more reliable lab results than the current two-dimensional assays and animal models. Any improvement in early stage drug candidate selection or reduction of late stage failure rates can significantly reduce costs and speed up timelines.
For example, imagine you are a pharmaceutical company and you learn that your top drug candidate for heart disease has a potentially fatal side effect on the human liver. You learn this during clinical trials, when you have already spent billions of dollars and exposed human test subjects to the drug. Now imagine learning about the side effect in your pre-clinical testing on 3-D tissue models — no patients will experience devastating results and you have saved five to ten years of effort and resources.
Development and validation of these 3-D assays requires substantial effort, but companies like Organovo are making significant headway, showing data that their 3-D bioprinted liver provides a predictive and reproducible model of human liver biology for preclinical toxicity testing in certain applications. This has the potential to be game changing.
Laura Bosworth is CEO and co-founder of Austin-based TeVido BioDevices, an early stage biotech start-up developing innovative, tissue engineered products for reconstructive surgery, with the first product targeted to improve nipple reconstruction after mastectomy due to breast cancer.