Very few infectious diseases in recent years have commanded the kind of attention and concern that Zika Virus has. Although Zika outbreaks have been reported in Africa, Southeast Asia and other parts of the world since the 1952, recent announcement by the Center for Disease Control and Prevention (CDC) confirming its link with microcephaly has forced everyone to sit up and take notice. The CDC estimates that the current pandemic is widespread with at least 50 countries reporting active Zika transmissions at this time. Most people with Zika virus infection will not have any symptoms though some may experience mild fever, conjunctivitis, muscle and joint pain, and headaches.
The virus is primarily transmitted by the Aedes mosquito. However, pregnant women may pass the infection to their babies, which may lead to microcephaly, a neurological condition associated with an abnormally small brain in the infant. The condition can lead to birth defects ranging from hearing loss to poor vision and impaired growth. Prompt diagnosis and treatment of Zika virus infections in pregnant women can, nonetheless, lower the risk of microcephaly to a great extent. Researchers have, therefore, put in a lot of time, money and effort to find a solution, and as always, three-dimensional (3D) medical printing and bioprinting technologies are leading the way.
Understanding the Disease
To begin with, 3D printing has played a crucial role in conclusively establishing the link between Zika virus and microcephaly. Researchers at John Hopkins Medicine used 3D bioprinting technology to develop realistic models of brain that revealed how the virus infects specialized stem cells in the outer layers of the organ, also known as the cortex. The bioprinted models allowed researchers to study the effects of Zika exposure on fetal brain during different stages of pregnancy. The models are also helping the scientists with drug testing, which is the obvious next stage of their research.
Zika Test Kit
Engineers at Penn’s School of Engineering and Applied Science, under the leadership of Professor Changchun Liu and Professor Haim Bau, have developed a simple genetic testing device that helps detect Zika virus in saliva samples. It consists of an embedded genetic assay chip that identifies the virus and turns the color of the paper in the 3D printed lid of the device to blue. This can prompt healthcare professionals to send the patient for further testing and to initiate treatment. Unlike other Zika testing techniques, this screening method does not require complex lab equipment. Each device costs about $2, making Zika screening accessible to pregnant women from the poorest parts of the world.
The scientists at the Autonomous University of the State of Morelos (UAEM) in Mexico are relying on the additive printing technology to create a microvalve that may help treat microcephaly in infants. The valve reduces the impact of the neurological disease and slows its progression by draining out excessive cerebrospinal fluid associated with this disorder. It can be inserted into the infant brain through a small incision to relieve fluid pressure and provide space for normal development. Researchers estimate the device will be available for patient use by 2017. These examples clearly demonstrate the impact of 3D printing on every aspect of the fight against Zika virus from diagnosing the disease to treating it. The results have been extremely promising, and both researchers and healthcare professionals are immensely hopeful that additive printing technology will help them overcome the infection quickly and effectively.
Physicians across the globe have relied on surgical interventions for centuries to treat complex illnesses and injuries. High quality surgical instruments have played an important role in their success. Nonetheless, healthcare professionals are constantly looking for tools that would improve patient outcomes and minimize the risk of unwanted complications. In recent times, three-dimensional (3D) medical printing and bioprinting technologies have allowed doctors and engineers to develop innovative tools that help perform invasive procedures with greater ease.
Robotic Surgical Tools
Mechanical engineering students at Brigham Young University (BYU), under the guidance of their professors Barry Howell, Spencer Magleby, and Brian Jensen, combined additive printing technology and the ancient art of Origami to create surgical tools that can fit through 3mm wide incisions. Inside the body, the tools can unfold and expand into complex devices such as D-core tools. Minute incisions allow for quick healing eliminating the need for sutures and scars. The tools are highly precise and effective as well. Researchers at BYU are now collaborating with California-based Intuitive Surgicals to manufacture their products. The company is using 3D printing to develop both the prototypes and the actual tools. The 3D printing technology is also helping Intuitive Surgicals to create instruments with fewer parts making the entire process more cost-effective and stable.
The Pathfinder ACL Guide
Orthopedic surgeon Dr. Dana Piasecki of the OrthoCarolina Sports Medicine has developed a 3D printed surgical tool to conduct ACL surgeries with improved success. Currently, most surgeons drill a hole in the patient’s tibia to remove the torn anterior cruciate ligament and replace it with a graft. The procedure is painful, and the graft often fails to anchor properly. The Pathfinder ACL Guide, created by Dr. Piasecki in collaboration with Strasys Direct Manufacturing, has a 95 percent chance of placing the graft at the right position and helping it withstand the stress associated with extensive movement. The surgical tool is made from a biocompatible and flexible metal and is significantly cheaper than the existing devices. The Pathfinder ACL Guide has been registered with the FDA as a class I medical device and can now help thousands of amateur and professional athletes to continue playing their game in spite of an ACL tear.
Eyelid Wands and Forceps
Similarly, Dr. Bret Kotlus, a New York-based cosmetic surgeon, has used 3D printing technology to create customized tools for eyelid surgeries. His stainless steel Eyelid Wand helps surgeons lift excess eyelid skin and point it to various facial structures as per the needs of the patient. The handle of the tool consists of a ruler for accurate measurements.
Dr. Kotlus has also developed 3D printed Pinch Blepharoplasty Marking Forceps that allow surgeons to mark excessive skin with a gentle ink. It comes with a round tip and a built-in ruler handle for additional patient comfort. These tools also add some sophistication to the doctor’s office at an affordable price. Close to 50 million surgical inpatient procedures are performed across the United States each year. While recent times have seen a significant improvement in the way these interventions are carried out, a lot can be done to make the process more efficient and safe. This is where 3D printing is bound to make a huge impact in the near future.
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3d printed eyelid instrument designed by Dr. Kotlus
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Since the 1980s, three-dimensional (3D) medical printing and bioprinting technologies have been influencing almost every aspect of the human life. Most people are, however, surprised at the kind of impact additive printing is having in the field of medicine. The technology is helping diagnose and treat complex illnesses ranging from cancer and heart disease to arthritis and infections. In recent months, several innovative 3D tools have also been created to overcome obesity. More than two-thirds of adults in the United States are obese or overweight. The prevalence of obesity has doubled in children and quadrupled in adolescents in the last 30 years. This has increased the risk of Type II diabetes, cancer and other serious conditions in men and women of all ages and abilities. Both government agencies and nonprofit organizations have spent millions of dollars creating awareness about the issue. Consequently, many people now understand the importance of healthy diet and exercise. They, however, lack resources that will help them accomplish such goals. Physicians are also looking for tools that will assist them in treating morbid obesity more effectively. Thankfully, 3D printing technology is offering some novel solutions to everyone, and researchers believe that it will ultimately bolster the efforts aimed at reducing weight and enhancing fitness levels.
BioSculpture Technology, under the leadership of New York Downtown Hospitals and the Presbyterian New York affiliated plastic surgeon Robert Cucin, is relying on 3D printing to develop an innovative line of surgical instruments to perform liposuction. The technology is also allowing surgeons to create exact replicas of the patient’s organs and practice the procedure before the actual intervention. Together, these products are making liposuction more accessible and safe. Liposuction is an invasive procedure that involves removal of excess fat from various parts of the body and is commonly used treat obesity. Close to 400,000 people underwent this surgery in 2015, as per the American Society of Aesthetic Plastic Surgery.
Exertion Games Lab in Melbourne, Australia, has created a simple device that can print 3D models of the user’s physical activity time, sleep time, and heart rate during the week to motivate and encourage them to set new challenges. Unlike smartphones and pedometers, the Exertion Games Lab device caters to the needs of children as it helps them grasp complex fitness-related information with ease. Children can also hold these models in their hands and share their enthusiasm with their peers.
These examples just form the tip of the iceberg. The impact of 3D printing on the fight against obesity is expected to go beyond creating mechanical devices and surgical instruments. Tamara Nair, a Research Fellow at the Centre for Non-traditional Security (NTS) Studies in the S. Rajaratnam School of International Studies (RSIS), believes that the technology can also be used to create food products with higher nutritional value. Such foods may help obese and overweight individuals manage calorie intake according to their activity level. The 3D printing technology can also make nutritious foods more palatable, says Nair. These potential benefits may appear like science fiction to some readers. Nonetheless, if the recent advances in the 3D printing and bioprinting technologies are anything to go by, they may turn into reality very soon.
In spite of extensive research, the medical fraternity has not reached a consensus on what causes cancer and how it should be treated. Nonetheless, almost everyone agrees that early and accurate diagnosis is crucial for successful recovery. In fact, early detection can lead to a 70 percent decline in cervical cancer mortality, as per the Canary Foundation. Early diagnoses of colon cancer can increase the patient’s five-year survival rate from 11 percent to 91 percent. Almost 100 percent of the patients with breast and prostate cancer survive for more than five years when the condition is revealed at an early stage. Consequently, millions of dollars are being spent on developing and improving diagnostic techniques such as MRI scans, CT scans, PAP smears and mammograms. While these procedures have been immensely successful, they can be very expensive and may not be accessible to everyone. Some screening methods are associated with bleeding and other unwanted side effects. They can also lead to false-positive and false-negative reactions. Surprisingly, three-dimensional (3D) medical printing and bioprinting technology is paving the way for newer cancer screening techniques that are more sensitive, specific and cost effective. The technology allows the user to deposit desired materials on a substrate in a specific pattern to create medical devices, implants and prosthetics as per the needs of the patient.
Simplified Blood Testing
Miriam, a 3D printed blood testing device from Miroculus, uses proprietary microRNA detection technology and digital microfluids to identify early stage cancer at the molecular level. The company is focusing on gastric cancer at this time and has collaborated with the National Institute of Health to conduct clinical trials for the diagnostic device. The goal is to provide doctors with a simple tool to identify patients who require additional testing. This can help save thousands of dollars in the long run and make cancer screening available to patients in the poorest parts of the world.
Printing the Ducts
Another major challenge is to identify malignant tumors accurately. Doctors estimate that about 20 to 50 percent of breast tumors become invasive. However, the oncologists cannot determine which ones would worsen with time and hence, end up treating every patient with expensive and harmful medications. Researchers at University of Pittsburgh Medical Center and Carnegie Mellon University are relying on the 3D printing technology to print the duct between the mammary gland and the nipple. They hope to use the duct to grow breast tumors artificially in the lab and detect biomarkers that identify potentially malignant tumors.
Israeli startup MobileODT has developed a 3D printed mobile accessory known as the Mobile Coloscope. The doctors can attach the accessory to any smartphone and use it to click magnified images of the cervix. The images can help diagnose cervical cancer at an early stage. A disproportionately large number of women die of cervical cancer in the developing world due to inaccurate and delayed diagnosis. MobileODT hopes their device will help physicians overcome this hurdle. The success of these prototypes is inspiring other scientists to find novel cancer screening methods using 3D printing. Several projects have received millions of dollars in grant money with both healthcare professionals and scientists betting heavily on this technology. Soon, 3D printed devices may change the way physicians diagnose and treat cancer, and thereby help lower mortality rates significantly.
Significant thinning or loss of hair can have a detrimental impact on the individual’s overall quality of life. Men and women with unhealthy hair often suffer from emotional issues and low self-esteem. The condition may also be indicative of an underlying medical problem. As per the American Hair Loss Association, two-thirds of American men experience some hair loss by the age of 35 and about 80 percent of them have significant thinning of hair by the age of 50. Approximately half of women over the age of 50 also suffer from serious hair loss. Apart from genetics and lifestyle, certain medications and infections can also contribute to the condition. You will find a variety of hair loss treatments in the market today ranging from herbal products to surgical interventions. However, none of these solutions have succeeded in producing dramatic results in a consistent manner. Researchers are, therefore, looking at three-dimensional (3D) medical printing and bioprinting to find products that really work, and their efforts seem to be paying off.
3D Printing Technology to Create Cranial and Hair Implants
AdviHair, a subsidiary of London-based AdviCorp PlC, has developed a unique set of cranial prosthetics known as the CNC Hair Replacement System. The company uses 3D printing technology to create implants that conform to the patient’s scalp measurement and skin color. The product can help conceal partial or full scalp baldness associated with Alopecia. Once the prosthetic scalp is placed in position, it behaves like regular hair. You can swim, wash and style it the way you want. The product is expected to benefit more than 6.8 million Americans suffering from Alopecia, an autoimmune disorder that occurs when the patient’s immune system destroys his own hair follicles. The prosthetics are ideal for individuals who cannot undergo transplantation or other Alopecia treatments. Cosmetic giant L’ Oreal has collaborated with French bioprinting company Poietis to print hair follicles that will enhance their understanding of hair biology. The process involves creation of a digital map that indicates the exact position of the living cells and other tissue fragments. The digital map is used to generate instructions for the printing process. A pulsing laser bounces off a mirror through a lens and knocks one micro-droplet of the bio-ink into its position. Approximately 10,000 such droplets are deposited each second. L’Oreal is hoping to use this technology to create products that will treat and prevent hair loss at a realistic price.
Improved 3D Printing Software for Hair Implants
Although 3D printed cranial prosthetics and hair implants are gaining popularity, many of them take several hours to print. Researchers at Massachusetts Institute of Technology’s Media Lab are, therefore, working on a software platform called Cilllia that allows users to print hair-like structures within minutes. Additionally, researchers at the institute are looking beyond the aesthetics to explore other major functions of the follicles including adhesion, sensing, thermal protection and actuation. Hair loss can be stressful and overwhelming, and the treatments can be expensive. Many patients experience poor results in spite of their best efforts. Scientists are now using 3D printing to overcome the drawbacks associated with conventional treatments, and their recent success is offering hope to the millions of hair loss sufferers across the globe.
Implantable medical devices help diagnose and treat serious health conditions ranging from anatomical abnormalities to cardiovascular illnesses and kidney diseases. Commonly used devices include implantable cardioverter defibrillators, pacemakers, intra-uterine devices, spine crews, hip implants, metal screws, and artificial knees. Recent years have seen a significant increase in the use of such implants, which has led to the creation of several innovative products with improved function. Batteries play a crucial role in the successful operation of certain implantable devices. Most products rely on lithium cells that are powerful and easy to use. These electrochemical power sources can, however, lead to toxic side effects. Some patients may also experience biocompatibility issues. Healthcare professionals, nonetheless, had limited options, at least until now.
The 3D Printed Battery
Researchers at Carnegie Mellon University are aiming to overcome the drawbacks associated with traditional batteries by developing biodegradable versions made from natural ingredients. They have developed a prototype battery that can provide 5 milliWatts of power for up to 18 hours. This energy is enough to deliver medications slowly over a span of several hours or to detect the growth of pathogenic bacteria within the body.
The battery is made from melanin pigment found in skin, hair and nails. The pigment protects the body by absorbing ultraviolet light and toxic free radicals. It also has the ability to bind to metallic ions and can therefore, transform into the perfect battery material. While melanin can form either the anodic or the cathodic terminal of the battery, magnesium oxide is used as the second terminal and the GI fluid comprises the electrolyte. The materials are housed in a three-dimensional (3D) printed capsule made from polylactic acid, or PLA.
A 3D printer allows researchers to deposit the desired materials on a substrate in a specific pattern. It was invented in the 1980s to create engineering prototypes. Soon, researchers began using 3D printers in the field of medicine to improve patient outcomes. The technology helps customize the shape and the size of the outer capsule as per the needs of the consumer. The 3D printed capsule maintains the structural integrity of the battery and allows it to glide smoothly through the device. The capsule can dissolve quickly once it completes the essential functions. Other natural components within the battery can also degrade without producing any toxic side effects.
Currently, most ingestible and degradable probes and drug delivery systems remain in the body for about 20 hours. Although melanin batteries are less powerful when compared to their lithium counterparts, researchers believe that they could work very well with devices that remain in the body for only a few hours. The new battery is in the initial stages of development and will need to undergo extensive clinical testing before actual use. Nonetheless, it is a step in the right direction. Eventually, it may be possible to create more powerful versions of edible batteries that can support all types of medical devices, irrespective of their duration of use.
In August 2015, the U.S. Food and Drug Administration (FDA) approved the first three-dimensional (3D) printed drug for commercial use when it allowed Pennsylvania-based Aprecia Pharmaceuticals to manufacture and market its anti-epileptic pill Spritam. The company relied on additive printing technology to create a rapidly dissolving pill that could be consumed with very little water. One of the main goals was to benefit patients who are unable to swallow medications, especially during an epileptic fit.
The licensed ZipDose technology used by Aprecia Pharmaceuticals combines formulation and material science with additive printing technology. The process involves deposition a thin layer of the powdered medicine on a substrate followed by the addition of a liquid to bind the particles into porous layer. The process is repeated multiple times to create a pill of the desired size and concentration. The success of Spritam has encouraged Aprecia Pharmaceuticals to use ZipDose technology to develop medications for other serious illnesses as well.
Dosage – Additive printing allows pharma companies to print drugs at specific dosages. Consequently, the patients do not have to suffer from poor prognosis associated with low-dose medications or consume high doses of drugs that can lead to unwanted side effects. As 3D printing technology becomes more prevalent in the pharmaceutical world, doctors can request for a specific dose of the drug instead of choosing from the available options.
Solubility – Although rapidly disintegrating, porous pills have been in use for several years, they usually provide lower doses of the active ingredient. Three-dimensional printing technology has allowed Aprecia Pharmaceuticals to add up to 1,000 mg of the potent drug into one Spritam pill while retaining its solubility. This can benefit a large section of the population including young children, elderly, and patients suffering from complex neurological disorders.
Compatible shape – Additive printing also helps produce pills in a variety of shapes and sizes, as per the needs of the consumer. Drug companies can produce small batches of the drug based on specific demand.
Distribution of Production and Distribution – Unlike large machines, 3D printers are easy to setup and operate. The manufacturer can shift the production of the drug to a location that is closer to the consumer and thereby, lower transportation and distribution costs and reduce wait times for patients with potentially life-threatening conditions.
Simplify Research and Development - 3D printing can also simplify research and development of new medications by making the process more efficient and cost-effective. Potential compounds can be printed in the laboratory and tested on 3D printed organs and cell lines for immediate results.
Recent developments in additive printing have forced most drug companies to sit up and take notice. They are investing millions of dollars in the technology to speed up drug development. While the time to replace medication prescriptions with printer algorithms is not yet here, 3D printing is bound to have a huge impact on the way companies develop and manufacture drugs in the near future.
The three-dimensional (3D) medical printing and bioprinting industry is evolving at a rapid pace as 3D printers continue to move beyond research labs into commercial manufacturing facilities and hospitals. The printers are being used to create anatomical models, customized implants and even body parts that help treat, manage and prevent complex illnesses and injuries. The technology has contributed to the success several challenging surgical interventions in the recent times.
Three-dimensional Printing Systems
While scientists are using 3D printers for a variety of purposes, most physicians are relying on them to create patient-specific models of targeted organs and tissues. Healthcare professionals obtain accurate dimensions of the patient’s body parts from radiological images and feed the information into a computer to print exact replicas of the organs. These models help the surgeons assess the abnormality with precision and practice the surgery before the actual procedure.
Several consumer-friendly 3D printing systems have been created to meet these needs. Belgium-based Materialise offers Mimics inPrint system that allows physicians to directly import patient images from hospital PACS and use them for 3D printing. The product comes with DICOM compatibility that supports all types of imaging machines. The semi-automated segmentation and editing tools within the printer’s software system ensure error-free printing and enhanced communication. Materialise sets up the entire system and trains the hospital staff to operate it efficiently.
Stratasys Inc. also offers additive printing technology to hospitals across the globe. It has the widest variety of materials ranging from clear, rubberlike and biocompatible photopolymers to rigid and flexible composite materials in over 360,000 colors. The Medical Innovation Series from Stratsys has been created for physicians, medical device designers, clinical educators and other professionals in the healthcare industry.
Twelve National Health System (NHS) hospitals in the United Kingdom are relying on Stratsys printers to create models that allow surgeons to analyze patients’ condition, test implants and practice surgical interventions for better outcomes. Most popular 3D models at NHS hospitals include jaw bones for facial reconstruction surgeries, hip models for hip replacements, forearms for repairing deformed bones, and cranial plastics for fixing holes in a person’s skull.
Doctors Without Borders, the Italian humanitarian organization, is also using 3D printed replicas of hospital models to setup new ventures in remote areas of the world. The technology allows physicians to have a realistic experience and thereby, improve patient care.
Several other healthcare facilities are also using additive printing technology for increased efficiency. Physicians at Hong Kong’s Queen Elizabeth Hospital used 3D printing technology to help a 77-year-old woman suffering from two damaged valves. The patient had already undergone three open heart surgeries and needed a complex fourth intervention. The 3D printed model helped the doctors complete the surgery in just four hours. In another case, surgeons at Children’s Hospital in Colorado and engineers at Mighty Oak Medical created a 3D model of a patient’s spine to rehearse the surgery. The physicians also used additive printing technology to print customized brackets to treat the patient’s scoliosis.
These success stories are inspiring other hospitals to install 3D printers at their facilities. They would, however, require expertise to handle the printer and tools to eventually use the 3D model for clinical purposes. Several facilities are incorporating 3D printing training programs to build knowledge within the institution and to lower the lead times for the actual procedure. While the initial investment may appear significant, most experts agree that 3D printing technology can be a game changer as it can help physicians improve clinical outcomes and reduce costs associated with complicated surgical interventions.
Advances in science and technology are helping pharmaceutical companies and biotech giants to come up with novel molecules that may help treat serious and life-threatening conditions such as cancer, heart disease, and Alzheimer’s disease. However, bringing a new drug to the market can get complex and exhaustive. While most companies pass through the initial stages of drug development with ease, they face a lot of challenges during pre-clinical and clinical trials. Recent numbers reveal that only one in 5,000 drugs become accessible to patients. The biopharmaceutical industry spends over $31.3 billion on research and development each year. They also face a lot of ethical questions related to animal testing. Nonetheless, this scenario may soon change as additive printing technology becomes more accessible and dependable.
Additive printing, also known as three-dimensional (3D) printing, involves deposition of desired materials on substrates to obtain 3D objects with specific dimensions and characteristics. Many different types of 3D printers are available in the market. Some machines help the user print mechanical and non-living objects. Others can print living tissues and cells when relevant biomaterials are added in controlled environments. Researchers across the globe have already succeeded in printing complex tissue fragments and even small organs such as ears using 3D printers.
3D Printed Systems for Drug Testing
Organovo, a leader in 3D printing technology, has created multicellular, dynamic and functional 3D human tissue models for research and pre-clinical testing. As per the company’s website, the printed tissue will remain viable in vitro for a significant period of time while exhibiting all the structural and functional features of the actual tissue. Pharmaceutical companies can use these fragments to study the impact of new drugs on human cells and to predict the final outcome with greater accuracy. Organovo claims that its exVive3D will help researchers “assess biochemical, genomic, proteomic, and unique histologic endpoints.”
Nano3D BioSciences, a Texas-based startup, has collaborated with AstraZeneca and LC Sciences to develop a cell-based assay system to assess the effects of a panel of vasodilating and vasoconstricting compounds. The company hopes that the assay will soon become a standard in toxicity testing and in the development of cardiovascular drugs.
Similarly, a Canadian company, Aspect Biosystems, allows researchers to create customized tissue fragments for drug testing. The researchers will place specific cells in a hydrogel and print tissue fragments that are allowed to grow in an incubator until they achieve the desired dimensions. The components will resemble the target tissue in structure and function.
Researchers at University of California, San Diego, have printed tissue fragments that closely mimic the human liver. According to Shaochen Chen, a NanoEngineering professor at the University, most companies spend 12 years and about $1.8 billion to create one FDA-approved drug. Their 3D printed liver tissue can help companies to perform pilot studies with minimal effort instead of waiting for animal testing or clinical trials, and thereby save millions of dollars.
Apart from making pre-clinical trials more accessible and efficacious, 3D printed tissues also help drug companies overcome ethical issues associated with animal testing. Most researchers agree that animal testing is expensive, time-consuming and often inhumane. The animals require a lot of care, and this limits the number of tests that can be performed at a time. Additionally, results obtained from animal testing may not correlate with actual results in humans.
The 3D printed tissue fragments help overcome such obstacles and may eventually allow drug companies to simplify research and development. In the long run, it may also help reduce costs and make therapeutics more accessible and effective for everyone.
The three-dimensional (3D) medical printing and bioprinting market has exploded in the last decade with the invention of several new printers that can print everything from anatomical models to living cells. Each new machine has contributed in its own way to the success of this industry. However, only a few of them have impacted the field of medicine the way BioBot 1 has done in the recent years.
BioBots, a Philadelphia-based startup, hopes to use 3D printing technology to cure diseases, eliminate organ transplantation wait times, reverse climate change, and promote life on other planets. Their BioBot 1 desktop 3D printer is capable of printing live tissues from human cells. The low-cost machine is making bioprinting technology accessible to everyone from major universities to small research labs and is thereby, helping transform medicine and biology.
The History of BioBiots
The BioBots printer began as a dorm room project for two of its co-founders who were biology and computer science students at the University of Pennsylvania. Their initial prototype won a university competition and a $50,000 grant through the Dreamit Health program. The team began building smaller, cheaper and more efficient printers and is currently targeting biotech and pharma majors that spend millions of dollars on clinical research. The printer may help the companies generate specific cells lines and tissue fragments to test their therapeutics.
Unique Features of the BioBots Printer
The popularity of the BioBots printer is not without a reason. The machine comes with several novel features and a small footprint. It can essentially fit into most bio-safety hoods and allows the researchers to work in a sterile environment with ease. The printer uses standard petri dishes and 96-well plates to simplify the printing process. The user can upload designs, choose biomaterials and eventually print the tissue fragments with minimal effort.
The BioBots 1 printer uses visible blue light to cure biomaterials quickly without damaging the cells. It includes a compressed air pneumatic system with a pressure range of 0 to 10 PSI that accommodates a variety of viscous materials and helps achieve specific start and stop points. The linear rails guarantee 10-micron precision. The printer also has two heated extruder heads to achieve temperatures between room temperature to 120 degrees.
BioBots 1 printer also differs from its rivals in the type of bioink it uses. The support material maintains the structural integrity of the cells during the printing process and prevents their degradation after the printing is complete. The user also opts for a scaffold or a matrix gel prior to adding the cells and printing the final tissue fragments. BioBots offers a large selection of products for its printers including support bioinks, sacrificial bioinks, matrix base reagents, matrix ECM proteins, matrix print enhancers, and curing bioinks. The company has also created a bioink open source allowing researchers to improve the technology further.
Potential Uses of BioBots Printers
Although BioBots is currently pitching its product to companies and research institutes involved in drug development, most experts are hopeful that the use of this printer will expand further to benefit patients waiting for organ transplants. Researchers at Drexel University are using the BioBots 1 to print bone tissue while University of Michigan professors are using it to print nerve tissue. Physicians may soon be able to print compatible body parts with lower risk of rejection prior to transplantation surgeries for greater success.
BioBots 1 printer definitely holds a competitive edge due to its small foot print, ease of use, wide selection of bioinks, and lower price. The company is investing millions of dollars on improving the performance of the machine, and if recent developments are an indication, the BioBots is bound to play an important role in diagnoses, treatment and prevention of complex diseases in the near future.
Three-dimensional (3D) printing technology was invented in the 1980s to create mechanical prototypes for the manufacturing sector. Healthcare professionals and researchers soon realized the potential of this novel technology in the field of medicine and began depositing desired materials on specific substrates to create anatomical models, surgical instruments, prosthetics and even body parts that could be customized to meet the needs of the user. Scientists rely on MRI and CT scan images of the patients to obtain the exact dimensions for the target object, feed the image data into one or more software programs, and let the 3D printer do its job.
Millions of dollars have been spent on 3D medical printing and bioprinting research in last decade, and such endeavors have led to the creation of several innovative solutions. Nonetheless, many of these products can't benefit the patients until they come with the Food and Drug Administration’s (FDA) seal of approval. Recently, the federal agency woke up to the needs of the 3D medical printing industry and issued guidance for 3D printed medical devices based on design, manufacturing and device testing information. Many 3D printed products have received FDA approval, some of which are highlighted below.
The O2 Vent a 3D Printed Solution for Sleep Apnea In April, 2016, Oventus, an Australian startup, received FDA approval for its titanium mouth device called the O2 Vent. The customizable oral device contains airways that reach the back of the patient’s mouth bypassing obstructions caused by nose, soft palate or tongue. The 3D printed device is expected to benefit over 37 million Americans suffering from sleep apnea while helping Oventus enter the $50 billion global sleep disorder market.
Spritam, the FDA approved 3D Printed Drug In another bold step, the FDA approved a 3D printed drug, Spritam, to treat partial onset seizures, myoclonic seizures and primary generalized tonic-clonic seizures. Its manufacturer, Aprecia Pharmaceuticals, used the ZipDose 3D printing technology to create a pill that disintegrates in the mouth with very little water and is especially beneficial to patients who cannot swallow their medication during seizures. The high-dose drug can impact over 2.4 million American adults with epilepsy, as per an article published in the March, 2016, edition of Forbes.
Lateral Spine Truss System Another innovative product, the Lateral Spine Truss System, also received a go-ahead from the federal agency in 2016. It consists of 3D printed orthopedic implants, manufactured by 4WEB Medical, that allow for integrated instrumentation and customization. They come in sterile packs and can be used with most mainstream spinal surgery techniques. The goal is to deliver functional implants with a structural design.
CASCADIA Cervical and CASCADIA AN Lordotic Oblique Interbody Systems The FDA has also issued a 510 (K) clearance to K2M for CASCADIA Cervical and CASCADIA AN Lordotic Oblique Interbody Systems with Lamellar 3D Titanium technology. While CASCADIA Cervical Interbody System is an intervertebral body fusion device, the CASCADIA AN Lordotic Oblique Interbody System has been designed for transforaminal-lumbar interventions. K2M expects its product to help the approximately 800,000 men and women who undergo cervical fusion each year.
3D Printed Cranial Implants Brazilian and U.S. based BioArchitects collaborated with Swedish 3D printing company ArcamAB to generate patient-specific cranial implants. The company used Electron Beam Melting technology and lightweight titanium alloys to form the implants. Although the FDA approval is restricted to the non-loadbearing bones of the skull and face, healthcare professionals are hopeful that the technology can treat a variety of conditions ranging from trauma to congenital abnormalities.
While 3D printed products with FDA approvals strive to become more accessible to all patients, others are waiting in the pipeline for a green light from the agency. Licensing requirements include extensive lab testing and clinical evaluation. Doctors and scientists are, however, confident the products will meet the criteria and get the necessary endorsements from the FDA to eventually help transform medicine.
When a 77-year-old patient at Hong Kong’s Queen Elizabeth Hospital needed a complex heart surgery, the surgeons at the facility relied on three-dimensional (3D) medical printing for additional support. The patient was suffering from two damaged valves and had already undergone three open heart surgeries. Her body was not ready for a fourth intervention. The doctors decided to replace the damaged valves by making a small incision through her blood vessels. However, such an intervention had never been performed. A 3D printer helped the doctors create an exact replica of the patient’s heart and practice the intervention several times. They completed the actual procedure successfully in just four hours.
3D Printing Heart Helps with Cardiovascular Surgical Planning Surgeons at pediatric cardiac surgery center at the People’s Hospital in China also used a 3D printed model of the patient’s heart to analyze the anatomical abnormalities closely prior to the surgery. Their nine-month-old patient was born with malpositioned pulmonary veins and an atrial septal defect. The surgeons acknowledged that the anatomical model contributed significantly to the success of the intervention.
Researchers in other parts of the world are also looking at additive printing or 3D printing technology to treat and manage cardiovascular illnesses more efficiently. The technique involves deposition of desired materials on a substrate in a predetermined manner to print an object of choice. Healthcare professionals believe that this revolutionary tool will help millions of patients suffering from heart disease and stroke. An estimated 17.5 million people died globally from such conditions in 2012, as per the World Health Organization. They were also responsible for one in four deaths across the United States, as per the Center for Disease Control and Prevention.
3D Printing Blood Vessels The use of 3D printing technology is not limited to the creation of anatomical models. Scientists at Saga University in Japan used the Kenzan method of 3D printing to develop 2mm by 5 mm blood vessels for patients with myocardial infarction. The researchers used tiny vertical spikes to position the cells and form tubular structures in a nutritious broth. Traditionally, cardiologists replaced the damaged blood vessels of the heart with healthy ones from other parts of the body. However, finding compatible replacements without impacting other physiological functions has been a challenge. The 3D printed implants can be customized as per the needs of the patient and can be used to replace the damaged veins and arteries with precision. Cyfuse Biomedical is employing tissue engineering techniques as they work to bring bioprinted nerves, blood vessels, cartilage, liver and heart muscle to the clinic.
3D Printing Heart Valves In another instance, scientists at Denver University custom printed heart valves that are the replicas of the original ones. Researchers obtained specific dimensions of the valves from CT and MRI scans and bioprinted them in just 22 minutes. Denver researchers are currently working to improve the biocompatibility of the 3D printed valves. The ultimate goal is to design patient-specific implants with a low risk of graft rejection.
Given these developments, healthcare professionals and scientists are immensely hopeful about the development of a 3D printed heart. The biggest challenge, lies in creating a network of functional blood vessels that will allow the organ to survive in the body for a prolonged period of time. While the idea of printing a human heart may seem far-fetched, it is evident that 3D printing is influencing cardiovascular disease management in a big way.
Recent developments in the field of three-dimensional (3D) medical printing and bioprinting can revolutionize the way doctors approach ear disorders. The technology, also known as additive printing, allows the user to deposit a desired material on a specific substrate in a pre-determined manner to create 3D prints with definitive shapes and sizes. Scientists and healthcare professionals are already relying on this technology to create surgical instruments, anatomical models, diagnostic tools, prosthetics and even body parts. These novel solutions are offering hope to more than 360 million men, women and children across the globe who suffer from some form of hearing loss.
3D Printing and Smart Phones Make for Easy and Affordable Diagnoses Recently, students of A&M Texas University’s chapter of Engineering World Health used a 3D printer to create LED ostoscope smartphone attachments that take pictures of the patients’ inner ears and help diagnose conditions contributing to hearing loss. Unlike traditional ostoscopes that cost hundreds of dollars, these smartphone attachments can be built for just $6.42. Doctors working in underprivileged areas of South Asia, Asia Pacific and Sub-Saharan Africa can depend on this imaging device for accurate diagnosis, prompt treatment and effective prognosis.
3D Printed Hearing Aids Ontenna, a simple hairclip with a built-in hearing aid, is another glowing example of the way 3D printing technology is impacting Otology. The 3D printed device picks up sounds between 30 and 90 decibles and translates them into 256 different vibrations and light patterns that allow the wearer to actually feel and see the sound. Ontenna was developed by Tatsuya Honda, a researcher and sign language interpreter, who worked closely with the deaf community and understood the drawbacks of traditional hearing aids. The device is currently in the testing phase and may soon be available for commercial use.
3D Printing and Ear Prosthetics In another pioneering attempt, physicians at Royal Hospital for Sick Children in Edinburgh, Scotland, under the supervision of Dr. Ken Stewart, adopted the 3D printing technology to treat microtia, a congenital disorder characterized by underdeveloped ears. Traditionally, children with this condition were required to lay down in an MRI machine for a significant period of time while the doctors obtained a 2D tracing of the normal ear. Understandably, most children were overwhelmed by the process and became fearful of it. Doctors in Edinburgh are now using a 3D scanner to obtain the exact dimensions of the child’s ear. A 3D printer then creates a replica of the organ, which is sterilized and used during the carving process. Dr. Stewart is also working with Edinburgh University’s Centre for Regenerative Medicine and Chemistry Department to bioprint an ear using the patient’s own stem cells and is very excited about the potential of 3D printing in managing hearing loss.
3D Printing the Ear A study published in the October, 2015, edition of the journal Nature Biotechnology revealed that researchers have succeeded in printing human-sized ears with the help of the Integrated Tissue and Organ Printing System (ITOP) and have implanted them into mice. The implanted organs retained their shape over the next two months and formed blood vessels and cartilages. Success of ITOP in animal models is a big step in the right direction as it will allow doctors to print complex ear implants that are stable and functional.
Most people take their sense of hearing for granted. However, many conditions ranging from infections and injuries to fluid problems can impact it. Physicians and patients are looking for treatments that will help overcome deficiencies associated with existing modalities, and 3D printing technology is helping them do just that. Sources: http://thebridge.jp/en/2015/08/ontenna-lets-you-hear-sounds-through-your-hair
Three-dimensional bioprinting and medical printing technologies are influencing the field of ophthalmology in a big way. Quingdao Unique, a Chinese bioprinting company, had announced in 2015 that they will be able to print 3D corneal implants within a year. Their products will be available for animal testing initially, and if everything goes as per plan, their 3D printed human corneas could be ready for clinical trials in the next two to three years. The company’s third generation bioprinter provides optimal conditions for cell growth with a temperature range of 0 to 50 degrees Celsius, humidity regulation range of 80 to 98 percent, and pH of 7.0 to 7.5. Quingdao plans to overcome strength and flexibility issues associated with most human implants by using the patient’s own cells for printing.
Ophthalmologists across the globe are very excited about this development. Corneal transplants help treat vision loss due to infections, congenital deformities and injuries. In fact, cornea is the most commonly transplanted organ in the United States with over 40,000 patients receiving a new one each year, as per the American Transplant Foundation. Yet, 53 percent of the world’s population does not have access to corneal transplantations, as per a global survey published in the February, 2016, edition of the journal JAMA Ophthalmology. Additionally, many patients experience complications when their immune systems reject the transplanted graft.
Three-dimensional bioprinting is, however, expected to change all that. Scientists and healthcare professionals can rely on additive printing technology to deposit patient’s own cells and other compatible materials in a pre-determined manner on a desired substrate to create patient-specific implants with a lower rate of rejection. The 3D bioprinting technology also accounts for the natural anatomical variations that exist among humans. Doctors can refer to radiological images of the patients’ eyes to generate implants that have the same dimensions as the original one. 3D Printing Aids in the Diagnosis of Glaucoma and Other Eye Diseases Dr. Andrew Bastawrous, a Kenya-based eye surgeon, created a smart phone app to diagnose eye diseases such as glaucoma, macular degeneration and diabetic retinopathy. The app relies on the patient’s perception of the various orientations of the letter “E” to provide the diagnoses. A small 3D printed adapter can be added to the camera of the smartphone to obtain an image of the retina on the screen of the phone while administering the test. This technology is helping Dr. Bastawrous diagnose and treat thousands of patients with eye diseases in underprivileged areas of sub-Saharan Africa.
Ophthamology Surgical Planning The use of 3D printing is not limited to corneal transplantations. Surgeons can use this technology to create models of the patient’s eyes and practice the procedure before the actual intervention. This preparation “would allow a full appreciation of the anatomic relationships between the lesions and the complicated surrounding structures,” as per an article published in the journal Investigative Ophthalmology and Visual Science. This invaluable tool has also transformed clinical practice and education. Researchers are using a 3D Systems Z650 printer to produce “highly realistic” 3D prints of orbits that offer enhanced visualization of the delicate nerves of the eye. The 3D models are made from non-human materials and thereby, help avoid the ethical questions associated with cadaver specimens.
These recent developments only form the tip of the iceberg. Nonetheless, they clearly exemplify the limitless possibilities of 3D printing in ophthalmology. The technology is bound to simplify the treatment of eye diseases and improve patient outcomes dramatically.
The knee joint is the strongest and the largest joint of the human body. It consists of the lower end of the thighbone, upper end of the shin bone, and the knee cap. The three bones are connected to each other with articular and meniscal cartilages that act as shock absorbers and help protect and cushion the joint. Degeneration of the knee joint due to age and overuse can cause unwanted friction and bone spurs. The condition, also known as osteoarthritis, is the most prevalent form of arthritis and is often seen in individuals over 50 years of age.
Osteoarthritis develops slowly and leads to worsening pain and stiffness of the knee joint, grinding or clicking noise during movement, and weakness in the knee. Treatment involves lifestyle changes, physical therapy, and viscosupplementation injections. Patients with severe form of the disease may require a surgical intervention. During the process, the doctor may remove cartilage from another part of the body and place it in the knee or may replace the damaged cartilage with plastic and metal implants. Researchers across the globe are now looking at three-dimensional (3D) medical printing and bioprinting technologies to create highly compatible, patient-specific knee implants that will increase the success rates of total knee arthroplasty by improving patient outcomes and lowering the risks of a revision surgery. Unlike traditional implants that come in a few specific shapes and sizes, 3D printed cartilages can be customized as per the needs of the patient. Surgeons can use the additive printing technology to print larger cartilages as well.
The Biopen: A Handheld Bioprinter Used During Operations A team of researchers and surgeons from St. Vincent’s Hospital, Melbourne, developed the Biopen, a type of 3D printer that helps doctors create cartilaginous tissue fragments during the actual surgical intervention. The surgeon can customize the size and the shape of the tissue as per the needs of the patient. Researchers predict that the medical-grade plastic and titanium Biopen will lead to 97 percent survival of the cells and will transform knee surgeries forever.
This technology may, however, have some drawbacks. The human cartilage is made of only one type of cell. Scientists, therefore, tried to grow the tissue by embedding specific cells in a hydrogel but the liquid medium may restrict cell growth and intercellular communication. Consequently, the new implant may not have the desired mechanical integrity. Additionally, the degradation of the hydrogel may lead to the formation of toxins that would inhibit cell growth. Hence, researchers began looking for other materials to create cartilage implants.
A New Bio-ink Holds Promise for Printing Cartilage Scientists at Penn State, under the supervision of Dr. Ibrahim T. Ozbolat, created tiny tubes from algae extracts, injected cow cartilage cells into them, and allowed the tubes to grow for a week to create tiny cartilage strands. A bio-ink made from these strands was fed into a specially designed nozzle of a 3D printer to develop cartilage tissues of the desired size. Although this 3D printed cow cartilage is weaker than its natural counterpart, it is definitely better than the hydrogel version. Dr. Ozbolat believes that the implants will strengthen once they get exposed to the pressure from the joints. His team also hopes to mimic the entire process using human cartilage cells.
The Center for Disease Control and Prevention (CDC) estimates that one in two Americans will be diagnosed with osteoarthritis by the age of 85. An estimated 249,000 children under the age of 18 also suffer from some form of arthritis. Additive printing technology is offering hope to millions of individuals looking to overcome pain and improve quality of life. While most of these products are still at an inceptive stage, researchers are trying to start clinical trials at the earliest and get the required approvals in the not-so-distant future.
Defects and deformities of the vertebral column can have a debilitating impact on the patient’s quality of life. Thirteen-year-old Jocelynn Taylor was no different. She was diagnosed with scoliosis, a condition characterized by an abnormally curved spine that may develop in children during one of their growth spurts. Jocelynn’s condition prevented her from being active in school and at home. Her vertebral column was also pushing her lungs and preventing her from breathing normally.
3D Printing Aids in Complex Spinal Surgery Unlike most scoliosis patients, Jocelynn’s curvature extended past 100 degrees and required a complex surgery. Physicians at Children’s Hospital in Colorado took up the challenge under the supervision of Dr. Sumeet Garg. They worked closely with engineers at Mighty Oak Medical to create a specific three-dimensional (3D) model of Jocelynn’s spine. The model helped Dr. Garg with pre-surgical planning. He also practiced the surgery several times prior to the actual procedure and was prepared for any eventuality that could have crop up during the intervention. The surgeon also relied on additive printing technology to print customized brackets to straighten the vertebral column. Since the surgery, Jocelynn has been able to live life to without any restrictions and is immensely excited about the upcoming school year.
Dr. Ralph Mobbs, a neurosurgeon at the Prince of Wales Hospital in Sydney, worked with an Australian medical device company to print an exact replica of a patient’s cervical spine and its underlying tumor. He used the model to understand the patient’s anatomy and practice the surgical intervention. In the past, doctors usually avoided such procedures as one small mistake could lead to permanent nerve damage and quadriplegia. The 3D model helped Dr. Mobbs successfully remove the patient’s tumor without impacting the surrounding nerves.
Approximately 276,000 people across the United States are living with spinal cord injuries. An estimated 7 million people suffer from scoliosis. About 24,000 men and women have malignant tumors in their spinal cord. People also suffer from other spinal conditions such as spondylosis and intervertebral disc degeneration. Additive printing technology is influencing the way doctors approach these conditions and is helping improve patient outcomes significantly.
3D Printing Spinal Implants Spinal tumors have also received a lot of attention in recent times. While their treatment often involves drastic measures, 3D printing is making it easier for patients to recover and rehabilitate quickly after the intervention. For example, surgeons in China had to remove a significant portion of a patient’s backbone along with the tumor to prevent the spread of his cancer. While the patient was able to beat the disease, he was unable to use his legs. Orthopedic surgeons at Beijing’s Third University Hospital, under the supervision of Dr. Liu Zhongjun, 3D printed patient-specific spinal implants to replace five missing vertebrae. The 7.5-inch long titanium mesh constructs allow the patient’s own spinal cord to grow over time, and the implant will automatically biodegrade over time.
Although some of these cases have received extensive media attention, they are not the only ones. Doctors across the globe are relying on 3D medical printing and bioprinting technologies to treat and manage many types of spinal conditions. In another important step forward,Oxford Performance Materials (OPM) received the Food and Drug Administration (FDA) approval for its spinal implant system designed to replace thoracolumbar vertebrae T10 to L1. The Connecticut-based company is now offering hope to thousands of patients with spinal trauma or cancer. The polymer construct met all the load-bearing and fatigue requirements of the FDA and is now available for patient use through specific distributors. OPM is working to expand its product line to include additional lumbar and cervical vertebrae. Other companies and research organizations are also looking for newer treatments that will help patients lead productive lives, in spite of their spinal problems. Collectively, these attempts will make 3D printing technology indispensable in the not-so-distant future.
The brain is arguably the most important organ within the human body as it controls major physiological and psychological functions responsible for growth and survival. Several conditions, including cancer, stroke, infections, inflammation, congenital deformities, and Alzheimer’s disease, can impair brain function and lead to serious illnesses and disabilities. Treatments may include medications, surgery and physical therapy among other things. Researchers across the globe are spending millions of dollars to improve patient outcomes and to enhance the quality of life of individuals with brain diseases. Three-dimensional (3D) medical printing and bioprinting are playing a crucial role in identifying new treatments and facilitating the implementation of existing ones.
3D Printing Brain Helps Doctors Treat Patients Human brain is a complex organ made up of over 100 billion neurons that form trillions of connections, known as synapses, to send and receive messages. Each neuron plays a specific role in the body, and minor errors during surgical interventions may lead to serious complications and permanent loss of bodily functions. Neurosurgeons often rely on MRI and CT scan images to understand the anatomy of the patient’s brain and the actual defect. While the images are fairly accurate, they provide limited information and tend to miss crucial aspects of the problem that may impact the surgery.
Doctors are looking at 3D printing to increase the chances of a successful outcome. Neurosurgeon Mark Proctor and plastic surgeon John Meara of Boston Children’s Hospital created a 3D model of the brain of an infant, who was born with a part of the tissue outside his skull. The physicians obtained specific measurements of the patient’s brain from scanned images and fed the data into a computer to generate the 3D model. The model helped the doctors study the patient’s abnormality in detail and practice the procedure prior to the actual intervention.
Harvard University researchers studied several MRI scans before printing a three-dimensional smooth brain of a fetus, equivalent to the one at 20 weeks of gestation. The researchers, then, coated the 3D-printed brain with a thin layer of gel to the mimic cerebral cortex and placed it in a liquid to study the formation of folds in the brain. The aim was to understand congenital brain folding abnormalities and to help improve life expectancies of babies born with such defects.
The use of 3D printing is not limited to the treatment of anatomical abnormalities. Researchers at Heriot-Watt University in Edinburgh are printing stem cells and other types of cells found in brain tumors using additive printing technology to recreate tumor-like constructs for the laboratory. The multicellular models are being used to study the anatomy and the physiology of brain tumors. Researchers are also relying on them to test new drugs and therapeutics that may finally help cure for this deadly disease.
3D Printed Microchips and Prosthetics Combine for a Sense of Touch Prosthetic arms and limbs have been in use for several decades. However, most devices were clunky and uncomfortable. Three-dimensional medical printing has helped create prosthetics that can be customized to fit the patient perfectly. Modern, robotic versions can also help the patient move the limb as required. St. Vincent’s Hospital’s Aikenhead Centre for Medical Discovery has coordinated with scientists at University of Melbourne, the University of Wollongong, and several other institutions to take prosthetic arm research to the next level by developing a 3D printed prosthetic arm with a sense of touch. The idea is to establish a direct connection between the prosthetic limb and the patient’s brain.
The researchers are relying on 3D printed muscle cells on microchips to communicate with implanted electrodes, natural tissues and cells. A prototype of this robotic arm is expected by the end of 2017. Apart from producing high quality prosthetic arms, this new technology may also help treat other serious illnesses, including epilepsy, by establishing connections between nerve cells and electrodes to translate brain signals.
Stroke and Alzheimer’s disease are one of the leading causes of death in the United States, as per American Academy of Neurology. Furthermore, 8 out of 10 diseases found in the World Health Organization’s list of three highest disability classes have a neurological origin. Three-dimensional medical printing and bioprinting are offering novel insights into brain diseases and neurological problems and are allowing scientists and physicians to find cures with a lasting impact.
Stem cell research has been plagued with innumerable controversies and ethical questions. Most researchers agree that these undifferentiated embryonic cells have the potential to treat serious conditions such as heart disease, diabetes, stroke, arthritis, and Parkinson’s disease. They may also help evaluate the impact of new drugs and therapies at the cellular level.
Scientists, however, must be able to differentiate the stem cells consistently within a controlled environment to meet their specific needs. Furthermore, obtaining these cells from five to six day old embryos may not be acceptable to everyone. The scientific community is, therefore, looking at three-dimensional (3D) bioprinting to overcome some of the obstacles associated with stem cell research and to make the treatments more accessible, efficient and safe.
3D Printed Stem Cells There have been multiple attempts to print stem cells in the laboratory. Nano Dimension, an Israel-based technology firm, recently filed a patent for 3D printed stem cells. The company collaborated with Accellta, which is known for its stem cell suspension and induced differentiation technologies. Researchers from both organizations worked together to accelerate the printing process with the help of a specially adapted 3D printer that can print billions of high quality stem cells per batch. Nano Dimension believes that its technology can benefit pre-clinical drug discovery and testing, toxicology assays, tissue printing, and transplantation.
Previously, scientists at Heriot-Watt University in Edinburgh created a cell printer that produced living embryonic stem cells. The printer, a modified CNC machine, was fitted with two bio-ink dispensers. The machine dispensed layers of embryonic stem cells and nutrient media in a specific pattern that was ideal for differentiation.
In another study, researchers at Tsingua University in China and Drexel University in Philadelphia developed homogenous embryoid bodies using the 3D printing technology. The process mimicked early stages of embryo formation that involves clumping of the pluripotent stem cells. Researchers of this study believe that these little building blocks will pave way for the creation of larger, heterogeneous embryoid bodies.
Recent Applications of 3D Bioprinting Bioprinted 3D stem cells are also being used to treat a variety of conditions. For example, researchers at ARC Center of Excellence for Electromaterials Science and Orthopedicians at St. Vincent’s Hospital, Melbourne, have developed a 3D printing pen that allows surgeons to create customized cartilage implants from human stem cells during the surgery. The handheld device offers unprecedented control and accuracy. The pen works by extruding the patient’s own stem cells along with a hydrogel. The cartilage tissue has a 97 percent survival rate and can heal the body over time. Researchers believe that this technology can also be used to create skin fragments, muscles and bone structures.
As part of the MESO-BRAIN initiative, led by Aston University, scientists differentiated human pluripotent stem cells into specific neurons on a specially defined 3D printed scaffold. The final structure was based on the outer layer of the cerebrum and included nanoelectrodes that enabled electrophysiological function of the neural network. The technology will help develop cellular structures for pharmacological testing and help find cures for complicated mental illnesses such as Parkinson’s disease and dementia.
Three-dimensional bioprinting technology is growing at a rapid pace, and scientists are using it to print stem cells as well. The 3D printed versions resemble the actual stem cells in structure and function without some of the drawbacks. Scientists and healthcare professionals across the globe are, therefore, excited about the limitless possibilities of 3D printing and its impact on stem cell research. Sources: http://www.tctmagazine.com/3D-printing-news/nano-dimension-accellta-3d-bioprinter-stem-cells/
Close to 26 million people suffer from some form of kidney disease, and one in three Americans are at risk, as per the National Kidney Foundation. Diabetes, high blood pressure, and family history often contribute to chronic kidney disease that can lead to kidney failure. Other conditions include cancer, infections, stones and cysts. Remedies could range from medications and chemotherapy to corrective surgeries and transplantation. Three-dimensional (3D) medical printing and bioprinting are transforming the field of nephrology by facilitating existing treatments and by improving the success rates of difficult surgical interventions.
Kidney Three-dimensional Models The kidneys are two bean-shaped organs consisting of over one million nephrons that filter blood and remove waste from the body. Their intricate structure complicates diagnoses and treatment of kidney diseases. Additionally, the organs are located right below the rib cage and are surrounded by several other sensitive and important body parts. Surgeries can, therefore, get problematic, especially without proper imaging.
Healthcare professionals are trying to manage these issues by generating exact replicas of the patient’s kidneys using 3D printing technology. The models help them understand the anatomy of the patient and the abnormality prior to the actual treatment. Physicians at Department of Urology and Kidney Transplantation at the University Hospital (CHU) de Bordeaux in France scan patients’ kidneys and use the images to obtain specific measurements of the organs. They feed the information into a computer and rely on a Stratasys’ color, multi-material 3D Printer, to print models of the actual organs. These color-coded replicas are assisting the doctors with pre-surgical planning, especially when dealing with inaccessible tumors and kidney sparring surgeries. Researchers believe that the 3D models help prevent nerve and blood vessel damage during the intervention and significantly lower the risk of serious post-surgical complications.
Physicians in other parts of the world have also started using such tools. In a recent case, surgeons at Intermountain Medical Center in Utah studied the 3D printed model of a patient’s kidney and her tumor prior to the surgery to avoid major mistakes during the procedure. The detailed model helped Dr. Bischoff successfully remove the tumor without damaging the kidney. In another pioneering case, surgeons at Great Ormond Street Hospital in London transplanted an adult kidney into a child. Surgeons created 3D printed replicas of the donor kidney and the child’s abdomen to ensure the kidney can fit in properly. They also used the model to practice the surgery prior to the actual procedure. Given the immense impact, researchers are working hard to create machines and materials that make 3D printing more accessible and affordable for everyone.
Can Bioprinting Create Transplantable Kidneys? At Fissell’s Kidney Project, doctors, scientists and bioengineers from a dozen different universities across the United States are collaborating under the supervision of Vanderbilt University Medical Center’s nephrologist and Associate Professor of Medicine Dr. William H. Fissell IV to create the first 3D bioprinted kidney for human transplantation. The goal is to develop a synthetic kidney with a microchip processor that acts as a mini dialysis unit. The implant will be powered by the pressure created due to natural blood flow in the body. The team expects clinical trials to begin by 2017. The National Kidney Foundation states that over 100,000 Americans are waiting for a kidney transplant with an average wait time of 3.6 years. About 13 people die each day waiting for a compatible kidney. If successful, the Fissell’s kidney project will offer hope to thousands of patients looking for a donor.
Kidneys plays a crucial role in waste removal and regulation of the blood pressure, and kidney diseases can have a debilitating impact on the individual’s quality of life. Three-dimensional medical printing and bioprinting are helping overcome some of the drawbacks associated with conventional treatments and are, thereby, helping improve patient outcomes.
Since the 1970s, modern dental implants have helped millions of patients suffering from tooth loss due to periodontal diseases and injuries. Their success encouraged researchers and dental professionals to come up with newer designs to improve patient care. As three-dimensional (3D) printing became more efficient and accessible, dental professionals also began using the technology to create customized dental implants. Recent Developments of 3D Printing in Dentistry Most 3D printers use additive manufacturing technology, which allows dental laboratory technologists to deposit desired materials on a substrate in a specific pattern. The technologists scan the patient’s jaw to obtain specific measurements and enter the data into a computer. The printer uses this data to create customized implants with unprecedented accuracy and fit.
Maxillofacial surgeons at Baruch Padeh Medical Center and A. B. Dental created 3D printed titanium implants to help a 64-year-old man suffering from a metastatic tumor at the back of his jaw. The condition affects 1 to 1.5 percent of people suffering from malignant tumors and is characterized by pain, difficulty chewing and disfigurement. The 3D printed custom-made implants reduced recovery time after the surgery and helped enhance the patient’s quality of life.
As part of another revolutionary research study, scientists from University of Groningen in the Netherlands have developed 3D printed teeth using antimicrobial polymers. These replacement teeth and veneers contain positively charged resin groups that kill the bacteria, Streptococcus mutans, by producing holes in its cell membrane. Analysis within the laboratory indicated that the treated new teeth suppressed the growth of pathogenic bacteria by almost 99 percent when compared to their untreated counterparts. Additionally, these teeth are made from inexpensive polymers that are readily available.
In another pioneering attempt, researchers at University of Louisville recently developed a fully digital dental surgery protocol using 3D scanning, CNC milling and 3D printing to restore lost teeth. This new procedure skipped several steps from the existing implant manufacturing techniques and thereby, made the surgical intervention more efficient and accurate. The researchers used a 3D scan to obtain specific measurements of the missing teeth and relied on a CNC mill to generate the implant. They created an exact replica of the patient’s oral cavity with a 3D printer to guide the dentist during the actual surgery.
Benefits of 3D Printed Implants While the above-mentioned examples offer insights into the rapidly growing field of 3D printed dental implants, multiple new inventions are happening as we speak. The ultimate aim is to overcome the drawbacks associated with traditional dental implants, which involve complex and invasive surgical interventions that are time-consuming and risky. The newer 3D printed implants allow dentists to replace lost teeth with pinpoint accuracy and minimal discomfort. The technology also allows surgeons to customize the implants as per the specific needs of the patient for more aesthetic results. Laboratory professionals can generate dental models and implants at a faster rate, thereby lowering the wait time for the patients.
More than 30 million Americans are missing all teeth from one or both jaws, as per the American Academy of Implant Dentistry. Over 3 million people have dental implants at this time, and this number is increasing by 500,000 each year. Dental surgeons across the globe hope that 3D printed implants will make treatment more accessible, safe and cost-effective for all the patients, and thereby, help them overcome tooth loss with dignity.
Difference Between 3D Medical Printing and Bioprinting The first three-dimensional (3D) printer was invented by Charles Hull in 1984. In the next 30 years, the technology advanced rapidly and evolved into a $3.07 billion industry by the end of 2013. The 2014 Wohler’s report expects this number to grow to $12.8 billion by 2018 and exceed $21 billion by 2020. Unlike the past, the use of 3D printing technology is not limited to prototyping and development of traditional consumer products such as cars and electronics. The technology has also revolutionized the field of medicine as scientists and healthcare professionals are using 3D printing to print everything from prosthetics and surgical instruments to medications and biological tissues. The goal is to develop highly specific therapeutics to manage complex illnesses and injuries.
What is 3D Medical Printing? A variety of 3D printers are available in the market today. While some versions are highly versatile, others have been specifically designed to create a particular type of product. Traditional 3D medical printers use inorganic compounds such as polymer resins, metal, plastic, ceramic and rubber among other things. The printer will deposit the desired materials on a substrate in a specific pattern that is based on the texture and the dimensions of the target object. Users often rely on scanned images of the target to obtain accurate measurements. Research labs, surgeons and corporations have used this technology to create surgical instruments, implants and models of various tissues and organs. How is Bioprinting Different? Traditional 3D medical printing and bioprinting are obviously inter-related and somewhat similar to each other. In fact, many people use the terms interchangeably. While both printers use the same basic additive printing technology, bioprinting and 3D printing differ significantly at the implementation level mainly because of the type of raw materials they use.
Bioprinters have been designed to deposit biological materials such as organic molecules, bone particles, cells and other extracellular matrices on a desired substrate. Unlike traditional 3D medical printing, this process involves complex designing and extensive scaffolding as it aims to generate multicellular structures that mimic the real tissue in structure and function. In most cases, the printer should be maintained within a controlled environment to retain the viability of the product. Organovo is a leading company in the field of bioprinting.
Currently, bioprinting technology is being used to print tissue fragments, dental and bone implants, medications, and prosthetics. The products can be customized as per the specific needs of the patient or the research study. Many pharmaceutical companies are using bioprinted tissue fragments to understand the actual impact of medications and other therapeutics at the cellular level. Surgeons are also hopeful that the highly compatible bioprinted implants and tissues will increase the success rates of transplantation surgeries. In fact, many products are already undergoing clinical trials.
As per TechNavio, a leading market research company, the bioprinting industry will grow at the rate of 14.52 percent between 2013 and 2018. Along with 3D medical printing, it is helping surgeons and other healthcare professionals understand the human body in great detail. The two technologies are complementing each other and are evolving together to change medicine forever. Sources:
In spite of significant improvements in the field of medicine, thousands of women die each year during child birth. In fact, the number of maternal deaths in the United States has increased from 7.2 deaths per 100,000 live births in 1987 to 17.8 deaths per 100,000 live births in 2011. This worsening trend has been a matter of great concern within the medical community. Healthcare professionals and scientists are looking for newer methods to lower the incidence pregnancy-related deaths, and three-dimensional (3D) medical printing and bioprinting are playing an important role.
The 3D Placenta Understanding the anatomy and physiology of the placenta is challenging as the organ appears only after the woman is pregnant. Many obstetricians and gynecologists lack the expertise required to promptly anticipate, diagnose and treat placenta-related conditions such as preeclampsia, which is the leading cause of maternal death across the globe.
Researchers at Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System and the Tissue Engineering & Biomaterials Laboratory, Fischell Department of Bioengineering at the University of Maryland have created a 3D printed placenta that replicates the complex cellular structures and extracellular matrices of the real human version. Scientists are using these 3D models to study special cells known as trophoblasts that bind to the uterine wall and promote the development of blood vessels required to nourish the fetus in the womb. Scientists predict that improper migration of the trophoblasts causes preeclampsia.
For a study published in the April, 2016, edition of American Chemical Society's Biomaterials, Science and Engineering journal, researchers injected a peptide, known as the epidermal growth factor, into a 3D printed placenta and observed its impact on trophoblast migration. Unlike 2D models that only allowed scientists to observe the movement of the cells, the 3D models helped researches analyze how the cells moved, and how they came together to bind to the uterine wall. The epidermal growth factor did produce some encouraging results and is currently undergoing further testing.
Overcoming Fetal Abnormalities The use of 3D printing has not been limited to preeclampsia and maternal well-being. A team of surgeons at Colorado Fetal Care Center used 3D medical printing technology to create a specific model of the fetus based on the MRI scans of the mother's uterus. The model helped them understand the infant's myelomeningocele and treat it in utero. As per the National Institutes of Health, this intervention can significantly lower the need for cerebral shunts after birth.
In another case, doctors at University of Michigan’s C.S. Mott Children's Hospital used 3D medical printing technology to help deliver a baby with a walnut-sized lump around the nose that would prevent it to breathe after birth. The surgeons created a 3D model of the fetus's head using dimensions from the MRI scans of the uterus. Analysis of this model helped the surgeons choose the right method for delivery.
Further advances in 3D medical printing and bioprinting will help scientists and doctors develop innovative solutions to treat and prevent pregnancy-related complications. In the near future, this technology will become more accessible to everyone and will lead to lower maternal and fetal mortality rates.
Broken bones can be immensely painful and debilitating. Broken bones account for over 6.8 million medical treatments each year at various hospitals, emergency rooms and doctor's offices across the United States. Most minor fractures can be treated using casts, braces and traction devices. Occasionally, surgeons also replace the broken or missing bone fragments using bone grafts. Grafts may be derived from the patient's own body (autografts) or from a donor (allografts).
Although autografts and allografts have been in use for decades, they have several disadvantages. It is often difficult to find a compatible bone fragment. Furthermore, these implants degenerate with time, and most patients require a replacement surgery after 10 or 15 years. This surgery can worsen pain and lead to other complications, especially in the elderly.
Three-dimensional Bone Grafts To overcome some of these deficiencies, researchers at University of Toronto, under the supervision of Professor Bob Pilliar, began looking for special compounds that can be used to form artificial bone grafts and fragments. They discovered calcium polyphosphate that makes up approximately 70 percent of a natural bone. Mihaela Vlasea, a mechatronic engineer at University of Waterloo, then developed an indigenous 3D printer that uses ultraviolet rays and light-reactive binding agents to fuse the calcium polyphosphate molecules into bone fragments. The implant has a porous structure that allows the real tissue to grow over time. Subsequently, the implant is broken down naturally in the patient's body. Apart from treating fractures, this technology can also be used to produce replacement joints and cartilages for arthritis patients.
The porous nature of the 3-D printed grafts, however, makes them brittle and unmanageable at times. Researchers at Nottingham Trent University are working to further strengthen the bone implants by growing unique crystal structures within the bone scaffold at sub-zero temperatures. This technique may also reduce the time required to print the bone fragments.
Talus Bone Surgeries Some healthcare professionals are already using 3D printing technology in patients. Dr. Mark Myerson, an orthopedic surgeon at Mercy Hospital, Baltimore, relies on 3D printing services offered by 4Web Medical to create customized ankle bones that can be implanted into the patient's feet to replace a broken ankle. He has used this technology to help patients with talus bone fractures, who tend to lose blood circulation in the area. Consequently, the bone dies and begins to crumble leading to a flat and painful ankle. 4Web Medical uses CT scans of the opposite (normal) foot to get the dimensions and the specific shape of the bone. It feeds this information into a computer and uses a 3D printer to produce a compatible implant. Dr. Myerson places these implants in the patient's ankles. The intervention has helped patients regain 50 to 75 percent of their ankle function.
The field of 3D bioprinting and medical 3D printing is still in its infancy. Scientists across the globe are investing significant amount of time, money and effort to develop more efficient and cost-effective techniques. Many products are undergoing clinical trials. Three-dimensional bones will soon be accessible to millions of patients suffering from bone fractures and bone defects.
Image Credit : mdmercy.com
Three-dimensional medical printing and bioprinting technologies are offering innovative solutions to dentists, orthodontists and other professionals treating complex gum diseases and related oral health problems. These treatments may benefit a significant portion of the 67.4 million American adults that suffer from such conditions.
Gum disease, also known as periodontitis, is characterized by swollen and bleeding gums, persistent bad breath, and loose teeth. If untreated, the condition can lead to serious complications including tooth loss. Many patients with gum diseases may require bone or tissue grafting. Traditionally, bone grafting involves implanting natural or synthetic bone fragments into the affected gums and allowing them to grow in a controlled manner to replace the lost teeth. Patients with damaged gums may require soft tissue grafting. During the process, a dentist will remove tissues from another part of the mouth and place them in the gums to treat them.
Bioprinting Bones and Gums While such treatments may be effective, the challenge lies in finding compatible bone and tissue fragments. Additionally, the transplanted parts may get reabsorbed without producing the desired results. Researchers at Griffith University's Menzies Health Institute in Queensland, Australia, have created an novel solution by regenerating gum and bone tissues using 3-D bioprinters. They have trialed these components in animal models, such as rats, sheep and pigs, and are now focusing on clinical trails in humans. The technology may soon be available for commercial use.
As part of the study, the Australian researchers scanned gums and oral cavities of animals and used the images to obtain specific dimensions of the missing parts. They created computer-aided designs and relied on a 3-D bioprinter to create the models. Cells, extra-cellular matrix and other components of the targeted tissue were fed into the bioprinter, which was maintained at an optimal temperatures for tissue development.
The Benefits of BioPrinting The researchers at Griffith's university have created scaffolds with bone and ligament compartments, and the technology has allowed them to recreate the entire architecture of the missing tissue with unprecedented accuracy. The 3-D printed tissue fragment can be customized according to the patient's specific needs. The researchers believe that this technology will eliminate the need for compatible bone and tissue grafts from the patient's own body. As a result, the surgical intervention will be easy to perform, less invasive, and cost-effective.
The bioprinting industry is evolving at a rapid pace. Researchers from other fields of medicine are also benefiting from this technology. It is only a matter of time before these printers become accessible to millions of patients with gum diseases and other oral conditions.
Organ transplantations and surgical reconstructions using autografts and allografts have always been challenging. Apart from the complexity of the procedure, healthcare professionals also have difficulty finding compatible donors. Autografts derived from one part of the body may not fit in completely at the new location causing instability and discomfort. As per the U.S. Department of Health and Human Services, about 22 people die each day due to a shortage of transplantable organs. Creating more awareness about organ donation is only part of the solution. Researchers have to look for other alternatives, and this is where technologies such as three-dimensional medical printing and bioprinting are making an impact.
Integrated Tissue-Organ Printing System (ITOP) Millions of dollars are being invested to develop technologies that will help healthcare professionals print muscles, bones and cartilages using a printer and transplant them directly into patients. The ITOP system is a big step in that direction. It was developed by researchers at Wake Forest Institute for Regenerative Medicine. They used a special biodegradable plastic material to form the tissue shape, a water-based gel to contain the cells, and a temporary outer structure to maintain shape during the actual printing process. The scientists extracted a small part of tissue from the human body and allowed its cells to replicate in vitro before placing them in the bioprinter to generate bigger structures.
Unlike other 3-D printers, the ITOP system can print large tissues with an internal latticework of valleys that allows the flow nutrients and fluids. As a result, the tissue can survive for months in a nutrient medium prior to implantation. Researchers have used this technology to develop mandible and calvarial bones, cartilages and skeletal muscles. The goal is to create more complex replacement tissues and organs to offset the shortage of transplantable body parts.
Polylaprocaptone Bone Scaffolds Researchers at John Hopkins are also developing 3-D printable bone scaffolds that can be placed in the human body. Their ingredients include a biodegradable polyester, known as Polylaprocaptone, and pulverized natural bone material. Polylaprocaptone has already been approved by the Food and Drug Administration (FDA) for other clinical applications. Researchers combined it with natural bone powder and special nutritional broth for cell development. The cells were added to a 3-D printer to generate bone scaffolds, which have been successfully implanted into animal models. Researchers at John Hopkins are now looking for the perfect ratio of Polylaprocaptone and bone powder that will produce consistent results. They will subsequently test their scaffolds in humans as well.
More studies are being done as we speak. Many surgeons have also started using 3-D printed tissues and bones to help their patients. In the next few years, this technology will become more accessible, affordable and effective and may change medicine forever.
Sources: Photo Credit: Wake Forest Institute for Regenerative Medicine Scientists 3D Print Transplantable Human Bone