Medical 3D printing has spawned a prototype industry chain in medical models, diagnostic and treatment instruments, rehabilitation aids, prosthetic limbs, teeth and artificial joints. There are heavy problems regarding the approval of 3D printing products, national policy decisions on such products, and the technology and materials encountered during the rise of the products. How to break through these bottlenecks and master the entire market direction and core technology has become the key to the long-term foothold of enterprises, and is also a common concern of clinicians and researchers.
The TCT Asia Perspectives team communicated with Professor Wang Jinwu of the Ninth People's Hospital of Shanghai Jiaotong University School of Medicine on this series of issues through an online interview during the epidemic. The interview was conducted by
The digital medicine team of Academician Dr. Kerong Dai and Professor Jinwu Wang has long been dedicated to medical 3D printing research, which mainly includes 3D printing preoperative models, surgical guides, orthopedic implants and biological 3D printing around the clinical needs of bone and joint. In response to the current development trend of the bone and joint field toward minimally invasive, personalized and precise, Prof. Wang's team is also committed to the standard development, registration and regulation of 3D printed medical devices to bring them into the ranks of approval levels and meet clinical needs. The development of metal 3D printing standards, biological 3D printing standards and 3D printing standards for rehabilitation aids have been completed and released as group standards.
"Based on the development of the standards, the team has also obtained the first 3D printing medical device registration certificate in China, and the first medical device registration certificate obtained by a wholly owned subsidiary of a university under the registrar system." Prof. Wang Jinwu introduced, "With the support of Shanghai Jiao Tong University, we established a medical device trial base and set up Shanghai Jiao Tong University Medical Device Registration and Innovation Service Center, which mainly undertakes the work of medical device testing, registration service and regulatory scientific research."
Compared with mass-produced artificial joints as well as traditional medical devices, 3D printed medical devices have relatively high costs in clinical applications and little room for corporate profitability when producing personalized bone and joint products. For this reason, with the support of the key special project of the Ministry of Science and Technology, Shanghai Jiao Tong University has established a medical device intelligent manufacturing cloud platform. Professor Wang illustrated to us the significance of establishing the platform through a simple example: a company may not necessarily make money by printing a tooth for 10,000 RMB, but the situation will be different if 200 personalized teeth are printed at once through 3D printing.
At the beginning of the medical device cloud platform, the personalized patient's disease database and the medical device template database of medical-industrial crossover are established. +The model of "Internet of Things + Artificial Intelligence". On the basis of artificial intelligence, it is possible to quickly and accurately screen out medical-industrial cross-templates that are close to personalized patient needs, after which only some simple planning and design are required. Such an intelligent manufacturing cloud platform can greatly save time, reduce enterprise costs, and facilitate future personalized medical device registration and certification and clinical application translation.
"Bio-3D printing has become an extremely promising technology for clinical translation in creating tissues and organs with physiological structural functions and capable of self-repair." Prof. Jinwu Wang said, "Thanks to bio-3D printing, we can now perform high-throughput drug screening through 3D printed organoids. For example, tumor cells of tumor patients are printed into multiple small units of the same tumor, so that the most effective personalized drug for treating patients with that tumor can be screened." With the support of the Key R&D Program of the Ministry of Science and Technology, Prof. Jinwu Wang's team has also developed a bio-3D printing robot using the technology combination of bio-3D printing and robotics, which has prepared the experimental research aspect for the future entry of bio-3D printing into the field of minimally invasive treatment for bone and joint cartilage repair.
The main applications of Prof. Wang's team in the medical field are preoperative models and guides, 3D printed endoprosthesis and rehabilitation aids. Prof. Wang Jinwu focused on the application of orthopedic devices in the field of rehabilitation aids, which is summarized as "one old and one small".
The term "one old" refers to the fact that most people will develop inversion or valgus of the knee joint after the age of 60. The two main causes of knee pain are mechanical and inflammatory factors, of which mechanical factors can be treated with orthotics. Personalized 3D printed orthoses are lightweight, safe and effective for every patient who needs treatment. For some patients with early and mid-stage knee pain, it can significantly slow down the time to joint replacement or even eliminate the need for joint replacement. The 3D-printed knee orthosis developed by the team has not only obtained the medical device registration certificate, but also has been clinically applied in some hospitals in Shanghai and other provinces and cities.
The "one small" refers to the skeletal deformities that arise during the development of children can also be treated by 3D printed orthoses. There are two typical examples of orthotic applications, both of which are currently being researched by Prof. Wang Jinwu's team. One is scoliosis orthopedics, scoliosis in children was pointed out in the 2020 session of the two sessions has become the third "killer" after obesity, myopia, China's child and adolescent health, it is recommended that the prevention and control of scoliosis in children and adolescents as soon as possible.
The incidence of scoliosis is 3%-5% in the literature, but in recent years, many scholars have found through research and screening of a large sample of children that the incidence actually exceeds 10%. While it is possible to correct the scoliosis during development with the use of 3D printed orthoses, if left untreated, surgery is required after the scoliosis reaches approximately 40°. Surgery is expensive and traumatic for children and adolescents, and post-operative complications can result in paraplegia, which can have a significant impact on society and families.
Other problems in children are malocclusions, such as misalignment, retrusion, crowding or malocclusion, with a prevalence of over 80%. This condition can also be treated with 3D printed invisible braces. Above, thanks to the 3D printed medical appliance intelligent manufacturing cloud platform developed by the team, 3D printed orthodontic appliances can be made for children and elderly people quickly and easily.
The team of key R&D projects of the Ministry of Science and Technology led by Academician Dai Kerong and Professor Wang Jinwu has also achieved clinical translation through drug screening by bio-3D printing technology, which can clarify whether some drugs are hepatotoxic and nephrotoxic, in addition to personalized screening of tumor and other drugs.
Nature reported the bio-3D printing project by Prof. Wang Jinwu's team of Academician Dai Kerong of the Ninth People's Hospital of Shanghai Jiaotong University School of Medicine. The development of the technology and the realization of the final clinical translation application are inseparable from the digital design, personalized 3D manufacturing and cloud platform of artificial intelligence and intelligent manufacturing. Shanghai Jiao Tong University has completed the initial construction of the disease library and expert template library, which will be maintained by dedicated AI and software engineers, doctors and related researchers.
Bio-3D printing is the crown jewel of the 3D printing field, and it uses a 3D printing material we call bio-ink. Bio-ink contains cells, factors, and some mechanisms composed of biological materials. In the field of cellular drugs, no cellular drugs have been approved in our country yet, and even for stem cells, they are mostly at the stage of clinical trials. Therefore, only when cellular drugs are approved first, bio-3D printing can achieve zero breakthrough in terms of registration certificate. At the same time, the preservation, quality control, pollution prevention and regulation of bio-ink are facing bottlenecks of safety and efficacy, all of which are currently difficult in clinical translation.
Professor Wang added: "Of course, our national Sichuan University academician Zhang Xingdong proposed the use of animal-derived type I collagen or bioactive materials with a certain structure as the main component, without additional growth factors and drugs, to induce the differentiation of stem cells into chondrocyte cell lines, and ultimately achieve the regeneration of articular cartilage, suitable for the treatment of focal articular cartilage defects caused by trauma, degeneration regenerative repair. If we use it as a biomaterial to print through bio-3D printing, it can be clinically translated as a bio-3D printed product in the future. Regarding this research direction, our team is also assisting the participating units of the relevant Ministry of Science and Technology projects to jointly promote the clinical translation work, and we have already completed the relevant animal tests and are also making relevant preparations before the clinical GCP at the Ninth Hospital, which is expected to enter the clinical trial stage soon."
Many stem cell drugs have already entered the clinic in Europe, America and Japan, and Prof. Wang believes that China will soon achieve a breakthrough from zero to one in this area as well. Especially in the field of digital medicine, China has gone from following Europe and the United States to running neck and neck with them, and now we have achieved overtaking in some fields.
With the continuous development of digital technologies such as 5G, artificial intelligence and metaverse in recent years, the whole medical field is also developing in the direction of informatization, intelligence and digitalization. In particular, medical devices are developing towards personalization and minimally invasive, especially with the breakthrough research progress of absorbable biomaterials, the development from inactive endophytes to biologically active personalized endophytes will be a major development trend in the future.
Professor Wang believes that digital medical technology, 3D printed medical devices and biological 3D printing will be a future direction in clinical translation, and the rate of future market development will be an accelerated process. With the development of technology and the deepening of aging, the application of personalized medicine will become more and more widespread. In particular, biological 3D printing robots, high throughput screening of 3D printed organoid drugs, and the development of 3D printed personalized medical device intelligent manufacturing cloud platform will all help to realize personalized, minimally invasive and intelligent medical treatment to better benefit the disabled and society.