The new research paper titled, “Intelligent Freedom Manufacturing of Complex Organs” is written by professor Xiaohong Wang (Figure 1), Founder and Director of both the Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, and the School of Fundamental Sciences, China Medical University (CMU). This research work reviews the pros and cons of the existing cell-laden rapid prototyping (RP) techniques for complex organ manufacturing.
Complex organ manufacturing is a new, high-level interdisciplinary field that requires the integration of knowledge and talents of various fields such as cell biology, computer, information, chemistry, mechanics, engineering, manufacture, biomaterials, and medicine. One can say that complex organ manufacturing is not an easy procedure. Wang compares this to building a nuclear plant as it requires intermingling of intricate architectural design, appropriate biomaterial selection, multiple cell type incorporation, advanced manufacture techniques, stem cell induction strategies and the means of coordinating these different procedures to form a large scale-up functioning organism.
According to professor Wang, the functions of a complex organ substitute rely upon its major constituent cellular types, bioactive agents, supportive structures and overall organization. Importantly, findings showed that a successful organ manufacturing technology depends largely on the natural polymeric hydrogel selection and design, and on the synthetic polymer integration and performance with respect to some specific mechanical and biological properties.
Until present, professor Wang is the first and only scientist who knows the significant gaps between simple tissue engineering approaches and complex organ manufacturing technologies. With the pluridisciplinary knowledge of biology, materials, chemistry, mechanics, and medicine, she has created several series of organ three-dimensional (3D) printing technologies and achieved numerous number one landmarks in this field (Figure 2-5). Each of them has advanced at least 10-20 years to other pertinent groups all over the world with respect to biomaterial selections, technical advantages and clinical practicabilities for complex organ manufacturing. Some intrinsic shortcomings in her home-made single-nozzle, double nozze, double-nozzle low-temperature deposition manufacturing (DLDM) RP devices for complex organ manufacturing have been demonstrated in this research. Wang suggests that multi-nozzle rapid prototyping (MNRP) equipments will eventually lead to the revolution of complex organ manufacturing (Figure 6). According to professor Wang, MNRP will make it possible to manufacture complex organs for clinical use in an easy, fast and reliable fashion.
Furthermore, findings showed the importance of a synthetic polymer necessary for supporting the whole 3D printed constructs, the anti-suture vascular networks, as well as other anti-stress structures. She is also the first one printing both cell-laden natural polymers and synthetic polymers into organic entities. Using a pioneered stem cell induction protocol, Wang has induced stem cells to differentiate into various complex organs according to different spacial effects. The complex organs she has made can be long-term preserved under low temperature. Wang points that stem cell induction protocols, multiple tissue maturation paces, and organ function preservation skills are critical factors that affect final results of complex organ manufacturing. The MNRP equipment has been stressed upon as it holds the promise to provide an accurate method for automatically manufacturing complex organs in which the multi-cellular biochemistry, key anatomical geometry and clincial treatment, from micro, to meso, and to macro at every scale, are fully controlled.
Professor Wang has suggested further studies in this field. According to Wang, “it is expected that the intelligent freeform complex manufacturing products will be outstanding synergic ‘nuclear power plants’ of many interdisciplinary experts and technicians in the fields of biology, material(s), engineering, and medicine.” The multidisciplinary efforts will reap great benefits and the resulted organ substitutes will virtually replace the functions of a solid complex organ, such as the liver, kidney and heart, in the near future.
This will eventually lead to a prolonged life span and will also help in improving the quality of life. With organ failure being a leading cause of mortality it is vital that there is extensive research in this field. This will help bring about a significant decrease in the number of people who fall prey to organ failure.
Figure 1. Two photos of Professor Xiaohong Wang
Figure 2. Three-dimensional (3D) bioprinting of cardiomyocytes, hepatocytes and adipose-derived stem cells (ASCs): (a) a pioneered 3D bioprinter made in Tsinghua Unversity, Prof. Wang’ laboratory; (b) schematic description of the large scale-up 3D constructs printed by the single-nozzle 3D bioprinter; (c) a grid 3D construct made from the cardiomyocyte-laden gelatin-based hydrogel; (d) cardiomyocytes encapsulated in a gelatin-based hydrogel; (e) hepatocytes in a gelatin-based hydrogel after 3D printing; (f) hepatocytes in a gelatin-based hydrogel after 3D printing; (g-l) hepatocytes in some gelatin-based hydrogels after certain periods of in vitro culture.
Figure 4. Three-dimensional (3D) bioprinting of adipose-derived stem cell (ASC)-laden gelatin/alginate/fibrin hydrogel for complex organ manufacturing: (a) a pioneered double-nozzle 3D bioprinter made in Tsinghua Unversity, Prof. Wang’s laboratory; (b) schematic description of the cell-laden gelatin/alginate/fibrin hydrogel and pancreatic islets being printed into a grid construct using the 3D bioprinter; (c) a large scale-up 3D printed grid construct being cultured in a plate for 5 days; (d) a grid ASCs and pancreatic islets-laden gelatin/alginate/fibrin construct after being cultured for 10 days; (e-k) ASCs in the gelatin/alginate/fibrin hydrogel after growth factor or no growth factor induction; (l) a control, showing ASCs cultured on a two-dimensional plate and induced into endothelial cells.
Figure 6. Schematic description of liver manufacturing using a home made four-nozzle 3D bioprinter, created in Tsinghua Unversity, Prof. Wang’ laboratory.