By Mianmian Fei, Junior Project Manager - Academic Relations
3D printing isn’t a new technology. Rather, it has been used for decades. However, its application was very narrow until recent advances made 3D printing a viable industrial-production technology with a myriad of applications. In its current iteration, 3D printing has the ability to create complex 3D geometries with precise microstructures. Taking advantage of sophisticated medical imaging techniques, it might soon be possible to design customized drug formulations and a variety of biomedical devices. In the 5th edition of our Connected Series on September 22nd, 2020, Dr. Yinyin Bao and his student Ms. Nevena Paunović, both from ETH Zürich, introduced to us some cutting-edge 3D printing techniques and their application in biomedicine.
Libing Gu (left), Head of Academic Relations at swissnex China, hosted the webinar with Dr. Bao (middle) and Ms. Paunović (right).
First, Dr. Bao, Senior Scientist at the Institute of Pharmaceutical Sciences at ETH Zürich, gave us a presentation titled “3D Printing with Light”. He kicked off his presentation by giving us examples on the applications of 3D printing to the fight against Covid-19, such as 3D-printed Charlotte valves and respirators. Indeed, 3D printing has great potential in personalized drugs and medical devices, but what exactly is 3D printing? Dr. Bao explained 3D printing as an additive manufacturing method. Different from the traditional subtractive manufacturing method which wastes a lot of materials, and the formative methods where extensive molds must be produced first, additive manufacturing method is straight-forward and neat. It can be divided into three steps as illustrated in the picture below.
Traditional subtractive and formative manufacturing vs. additive manufacturing (3D printing).
In this presentation, Dr. Bao specifically focused on light-based 3D printing, or photopolymerization 3D printing, which is characterized by high resolution and surface quality compared to its extrusion-based counterpart.
Recently, a number of new techniques have been developed, and Dr. Bao introduced a few promising ones to our audience. The most typical technique is stereolithography (SLA, or 立体光刻), which laid the groundwork for commercial additive manufacturing. SLA has been widely used in biomedical research. For example, it is used to produce hydrogel-based tablets and polybills with different geometries and drug components.
While SLA is the most typical light-based 3D printing method, the most widely used one in both industry and scientific research is the second generation of SLA called digital light processing (DLP, or 数字光处理). DLP has an additional digital mirror device (DMD) which converts laser beams into light with different shapes. DLP is used to produce multivascular networks and functional intravascular topologies, an advanced step towards 3D printed organs.
Another technique is continuous liquid interface production (CLIP, or 连续液体界面制造) with an oxygen permeable window which creates a “dead zone” in the printing process. This technique saves time and enables better resolution. One application is the anticancer drug absorber, which is implanted beside a tumor to absorb toxic from anticancer drugs and reduce side effects of patients.
The most recent technique is volumetric 3D printing (容积3D打印), which completely abandons the layer-by-layer method and uses a tomographic reconstruction method. Therefore, the printing time is reduced to less than one minute and can achieve the same resolution as the previous methods. Volumetric 3D printing can be especially useful for bioprinting, since cells growing inside living tissue constructs can maintain very high viability as a result of the short light irradiation.
The last technique Dr. Bao introduced is two-photon micro-SLA (双光子打印), which uses femtosecond laser as the light source. One of its applications is the production of cell-instructive 3D microenvironment, a research led by his colleagues Dr. Xiao-Hua Qin in the Institute for Biomechanics, and it has great potential in future tissue engineering research. However, two-photon micro-SLA requires bulky and expensive instruments as well as long printing time, so its application in biomedical research is still relatively limited.
Dr. Bao concluded his presentation by saying that he believes light-based 3D printing has great potential in clinical applications. However, this is not an easy task and requires scientists from different areas to collaborate. That’s why his collaboration with Ms. Nevena Paunović, PhD student in the Drug Formulation and Delivery group and a licensed pharmacist, is interesting. Together they try to tackle the problem of limited biocompatible and biodegradable materials for the use of light-based 3D printing.
In her presentation, Ms. Paunović gave a brief overview on what they are currently working on as a team. She began by presenting to us the case of the first 3D-printed personalized bioresorbable tracheal splint, which was used on a pediatric patient in the U.S. in 2013. The patient suffered from a disorder called tracheobronchomalacia, which causes a weakness in the system connecting the throat and lungs. While most children grow out of it by age 2-3, 10% of patients’ respiratory tracts collapse and they stop breathing completely. This 3D-printed splint is elastic and flexible and allows tissue to grow around. Most importantly, it will degrade after three years when the patient is able to breath on his own.
Personalized bioresorbable tracheal splints produced by 3D printing was approved by the U.S. Food and Drug Administration and used on a pediatric patient for the first time in 2013.
Seeing the potential of 3D printing for bioresorbable medical devices, the team is working on personalized bioresorbable airway stents by 3D printing to help patients suffering from obstruction in the upper part of their airways. There are two types of stents available in the market. Silicon stents is biocompatible but has a limited number of sizes and shapes, and metallic stent is considered permanent as it is difficult to extract after the implantation. The ideal stent, therefore, is personalized, biocompatible, biodegradable, thin, flexible, and can be quickly produced.
Currently, fused deposition modeling (FDM) 3D printing is used to produce customized airway stents, but the resolution is not so high and metallic properties are not ideal. Plus, it is not biodegradable. Additionally, there are FDM printed molds which can be used to produce personalized silicone stents through injection molding, but this procedure is not convenient in a hospital setting and can take two weeks.
To solve these problems, Dr. Bao and Ms. Paunović’s team is trying to implement digital light processing (DLP) 3D printing as it can produce stents with high resolution and surface quality in a short amount of time, and the small equipment needed is suitable for any hospital setting. However, challenges include low viscosity of resins and lack of biocompatible and biodegradable materials to achieve such high resolution and surface quality. Even when all requirements are satisfied, 3D printed objects are either elastic but weak, or stiff but brittle.
How digital light processing (DLP) 3D printing works.
Ms. Paunović concluded her presentation by saying that the biggest opportunity for 3D printing is personalized medicine, and compared to personalized drugs, personalized medical devices can benefit even more as the technology enables their production with high complexity at low price. She resonated with Dr. Bao that professionals in different areas need to work together to tackle challenges such as the lack of suitable materials as well as difficulty in achieving massive production and regulatory approval, so that patients can benefit from the amazing technology of 3D printing.
The webinar ended by a lively Q&A session in which a number of audiences asked questions regarding the information presented. One interesting question was whether there is a trigger for degradation of biodegradable materials. Ms. Paunović answered by saying that most of the biodegradable material they work on starts degrading immediately, but there are different ways to slow it down. Dr. Bao added that there are also ways to accelerate the degradation, such as adding different PHs or enzymes.
We want to express our thanks and appreciation for Dr. Yinyin Bao and Ms. Nevena Paunović for their interesting and in-depth presentations and thoughtful answers during the Q&A session.
Please find a link to the slides and webinar recording below:
