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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.
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.
Figure 2. Three-dimensional (3D) bioprinting of cardiomyocytes, hepatocytes and adipose-derived stem cells (ASCs).
Figure 3. A large scale-up 3D printed complex organ with vascularized liver tissue constructed through the double-nozzle 3D bioprinter created in Tsinghua Unversity, Prof. Wang’ laboratory.
Figure 4. Three-dimensional (3D) bioprinting of adipose-derived stem cell (ASC)-laden gelatin/alginate/fibrin hydrogel for complex organ manufacturing.
Figure 5. A large scale-up 3D printed complex organ containing both cell-laden natural polymeric hydrogel and synthetic polyurethane (PU) overcoat created in Tsinghua Unversity, Prof. Wang’ laboratory.
