By David K. Mills

The future of personalized medicine is closer than we think thanks to three-dimensional (3-D) printing. Advances in materials, equipment, and techniques are already enabling on-demand, highly customized treatments for patients, but there is more progress to be made in the area of additive manufacturing.

Developed in the early 1990s as a powder-based fabrication technology for the rapid prototyping of tools using metals and ceramics, 3-D printing uses a digital file to produce a 3-D object of almost any shape via an additive process that lays down successive layers of material. The availability today of affordable 3-D printers for home use, as well as hundreds of 3-D models on the Internet, has led hobbyists to eagerly adopt it as a convenient means for creating simple plastic objects rapidly, cheaply, and with an amazing degree of accuracy.

But developments over the past five years have shown that the impact of this technology is no longer restricted to simple materials and hobbyists. Thanks to the substitution of bioplastics such as polylactic acid (PLA) and polycaprolactone (PCL) for more commonly used resins and plastics such as acrylonitrile butadiene styrene, 3-D printing is now being used for the rapid printing of medicines, medical devices and prosthetics, and even human tissue.

Perfect for Personalized Medicine

While there are few models relevant to scientific research and medical practice, customizable compounds made with PLA and PCL permit the fabrication of heterogeneous physical objects or structures of high complexity, without loss of resolution, and which give designers control over features such as porosity and composition. The ability to control these features enables the design of unique, patient-specific devices or drug treatment regimes.

Because of its ability to produce patient-specific solutions, 3-D printing is currently being used and studied for a number of personalized medicine applications.

Prosthetic Devices

Today’s commercially available orthopedic prosthetic devices are typically expensive and do not have the requisite anatomical capabilities and features for patients to resume normal functionality after loss of a limb. Often, standardized prosthetic devices lack sophistication and are not customizable.

A team at the University of Michigan’s C.S. Mott Children’s Hospital used 3-D printing to fabricate a customized, bioresorbable splint to fix a patient's life-threatening tracheal defect.

But of the 185,000 amputations that occur in the United States each year, the majority are performed on extremities that vary significantly from one individual to the next, according to the nonprofit Amputee Coalition.

Three-dimensional printing can address the issues of cost and customization with prosthetic designs that are patient-specific and conformable to individuals’ unique needs. Portland, OR-based GRASP, a startup specializing in 3-D printing light, inexpensive, customizable prosthetic, is currently working on a mobile application that will enable individuals to submit photos of their stump so a personalized prosthesis can be fabricated via 3-D printing.

Bioresorbable Medical Implants

Many implantable devices used today are made from materials such as methyl methacrylate that cannot remain in the body indefinitely and therefore require a revision surgery after a certain period of time. But pairing 3-D printing with nontoxic, biocompatible, and bioresorbable bioplastics has enabled the creation of customized implants that can degrade inside the body, eliminating the need for further surgery.

In one example, a surgical team at the University of Michigan’s C.S. Mott Children’s Hospital in Ann Arbor, MI, used a computed tomographic image of a patient’s airway to map a life-threatening tracheal defect. The team then designed and fabricated a tracheal splint made entirely from PCL using laser-based 3-D printing. The device enabled the patient to achieve marked improvement in respiration and will dissolve in the body after once the patient’s own trachea recovers.

While procedures that use 3-D printing to fabricate custom medical implants are still in their infancy, they have gained traction in recent years. South Windsor, CT-based Oxford Performance Materials won FDA clearance for its OsteoFab patient-specific cranial and facial devices in 2013 and 2014, respectively.

Startup organicNANO is using 3-D printing to create customized, controlled drug-delivery devices.

In October 2014, FDA held a public workshop titled “Additive Manufacturing of Medical Devices: An Interactive Discussion on the Technical Considerations of 3D Printing.” As regulation of such devices becomes clearer, more patient-specific 3-D printed implants will likely follow.

Customized Drug Treatments

Three-dimensional printers are also being used to create customized, controlled drug-delivery devices designed to transport therapeutic drugs directly to targeted areas and then degrade safely in the body and be expelled.

Medical-grade, biodegradable, and biocompatible PLA and PCL beads, discs, and filaments can be loaded with antibiotics or chemotherapy drugs for a more focused drug-delivery system. This breakthrough could generate improved drug-delivery devices, implants, and catheters.

Ruston, LA-based organicNANO, a startup spun off from technology developed at Louisiana Tech University, is using this novel 3-D-printing technique to develop a way to reduce infection, deliver chemotherapeutic drugs for use in cancer treatment, and help prevent the spread of disease. The emphasis of the firm’s design is controlled timing and quantity of drug release, and it aims to develop a system that can support any type of drug (e.g., antibiotics, antifungals, chemotherapeutics). The company anticipates FDA approval of its product applications and market launch within two years.

Bioprinting

Organovo's 3-D bioprinter can create functional human tissue from human cells.

Bioprinting , a biological cousin of additive manufacturing that uses a 3-D bioprinter along with living cells and a scaffold to construct human tissue, is also advancing rapidly. During the process, cells and extracellular matrix are combined to make a bioink. Using inkjet printing, photolithography, and syringe-based extrusion, the bioink is deposited in reproducible and defined patterns.

Examples of recent applications of this technology include the printing of microvascular cells in fibrin, cartilage cells deposited within agarose or hyaluronic acid matrices, and aortic cells printed in the shape of a heart valve based on microcomputed tomography scans.1, 2, 3 While bioprinting is still in the development phase, 2014 witnessed the introduction of several 3-D bioprinters by Organovo, BioBot, and Bio-3D technologies. This year will likely see the use of 3-D printed tissues in clinical medicine.

Conclusion

We are in the early stages of a major technology revolution in personalized medicine enabled by 3-D printing. Additive manufacturing applications are expanding annually at a rate akin to those of personal computers during the 1980s or cell phones in the early 1990s, opening the door for on-demand, highly customized medical treatments. While additive manufacturing still must overcome significant regulatory, technical, and business challenges before it becomes mainstream in the medical industry, the technology will likely play a big part in placing personalized medicine within our grasp.

References

1. K. Jakab, et al, “Tissue engineering by self-assembly and bio-printing of living cells,” Biofabrication (2010).Biofabrication 2, no. 2 (2010): 1–14. 
2. Z. Izadifar, et al, “Strategic design and fabrication of engineered scaffolds for articular cartilage repair,” Journal of Functional Biomaterials 3 (2012): 799–838.
3. X. Cui and T. Boland, “Human microvasculature fabrication using thermal inkjet printing technology,” Biomaterials 30 (2009): 6221–6227.
David K. Mills, Ph.D. is a professor in the School of Biological Sciences and the Center for Biomedical Engineering and Rehabilitation Science at Louisiana Tech University. Reach him at dkmills@latech.edu .