Current Status and Challenges of Three-Dimensional Modeling and Printing of Tissues and Organs.

The goal of the annual United States–Japan cellular and gene therapy conference is to exchange ideas on cutting edge and diverse areas of biomedical research and enhance opportunities for collaborations among scientists from the United States and Japan. The conference is jointly organized by the Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (FDA), and the Ministry of Education, Culture, Sports, Science and Technology, Japan, under the US–Japan Cooperative Research Program. The 19th annual conference on ‘‘3D Modeling and Printing of Tissues and Organs’’ was held in 2016 at the FDA headquarters located at White Oak Campus, Silver Spring, Maryland. The delegates presented and discussed the current innovations in three-dimensional (3D) bioprinting of various anatomical structures and their potential use in regenerative medicine. Bioprinting involves depositing of biological materials such as extracellular matrix components, biomolecules, and biomaterials to construct living tissues and organs. This special issue is a culmination of talks presented in the meeting. Additive manufacturing (commonly referred to as 3D printing) is driving major innovations in many areas, including regenerative medicines. 3D printing is a set of processes that builds layers to create a 3D physical object from a digital model. The manufacturing typically includes laying down successive thin layers of one or more materials until the 3D object is created. A unique feature of 3D printing, as opposed to other manufacturing methods, is that it permits access to the inside of the object during the printing, allowing complex channels or lattice structures to be made. 3D bioprinting offers great precision and control of the internal architecture and outer shape of a scaffold and allows mimicking complicated structures found in biological tissues. Recent advances have assisted 3D printing of biocompatible materials, cells, and supporting components into complex 3D functional living tissues. In the past few years, the Center of Devices and Radiological Health (CDRH) at FDA has cleared several additively manufactured devices, including orthopedic devices, patient-matched implants, surgical guides, and maxillofacial implants and restorative devices. Research laboratories from around the world have bioprinted a number of prototype medical products such as cartilage and bones, liver, dental and craniofacial spaces, tracheal splints, cardiac myocytes, blood vessels, and pancreatic tissues. Just as the layer-by-layer (LbL) assembly offers potential capabilities to medical devices, the technology does have its own set of challenges. In October of 2014, CDRH hosted a public workshop on 3D printing to have an interactive discussion with industry and academia on the potential concerns involved in additively manufacturing medical devices. Some of these technical considerations are described in FDA documents available on the FDA 3D printing website and a recent technical review. In 2015, the FDA approved Spritam (levetiracetam), the first 3D-printed prescription pill to treat certain types of seizures in epilepsy patients. This oral medication is made through a 3D printing process instead of a stamped pill, which builds the porous pill by spreading layers of the drug on top of one another until the right dosage is reached. The 3D printing allows the pill to deliver a high dosage of medicine while being porous enough to dissolve quickly in the mouth. These attributes can be particularly beneficial for patients who have a hard time swallowing their medications. The speakers at the United States–Japan cellular and gene therapy conference presented talks on 3D bioprinting of different types of regenerative medicine products. They discussed the development of different biocompatible biomaterials to create vascular grafts and fabrication of 3Dprinted scaffolds for craniofacial bone and cartilage regeneration and organ tissues. For the bone defect in oral and maxillofacial region, conventional methods are clinically challenging because of the limited availability of transplantable autologous bone grafts and the complex geometry of the bones. But the advances in 3D printing technologies provide clinicians, engineers, and scientists with the ability to create patient-specific solutions for craniofacial defects. It allowed the fabrication of custom-made artificial bone (CT-bone) using alpha-tricalcium phosphate particles and a printing process based on computed tomography (CT). The clinical research conducted in Japan on patients with facial deformities showed maintenance of the original shape and