**4. Limitations**

While 3D printing in healthcare is becoming more prevalent and technological advancements appear promising across a wide spectrum of applications, there are some drawbacks which must be taken into consideration. The technology is evolving and long-term evidence for the benefit of 3D printing for various applications is unknown. The potential risks of basing decisions on or carrying out procedures with poorly executed models (due to errors at any stage of the model production pipeline) is yet unknown. Another challenge is the considerable time it takes to complete the pre-print component of the pipeline. While surgery is the most complicated and expensive part of the treatment process, the increase in pre-surgical time may outweigh some of the costs saved in reducing surgery. Detailed cost effectiveness studies, which consider the increase in manufacturing capabilities and pre surgical time, as well as the reduction in operation time and improved patient outcomes, are necessary to truly evaluate the impact of 3D printing on healthcare costs. Improving the segmentation and model design stages of the pipeline will strengthen the case for 3D printing as a cost effective healthcare technology and are therefore crucial areas of research. For example, when stateof-the-art convolutional neural networks for automatic organ segmentation are packaged for non-expert users [65] model production time may decrease. A final consideration is the range of materials available for 3D printing. Currently materials often lack the ability to mimic both the mechanical and imaging (ultrasound, optical, electrical and X-ray) properties of biological structures. Tuning the electrical or optical properties during phantom construction has been demonstrated in rigid plastic, are not readily transferrable to flexible materials. Further the choice between these properties is mutually exclusive, as the additives used control one property change the other [66–70]. Multimodal phantoms are an area of active research and gel wax which can be tuned to have specific optical and ultrasound imaging properties looks to be a promising material [71].

Obtaining regulatory approval has been previously outlined as a significant barrier for the widespread implementation of 3D printing technologies in medicine [72]. While these challenges are still largely in place, the publication of the FDA guidance [48] has shown a clear pathway for full regulatory approval with these devices, with over 100 devices having undergone pre-market approval.
