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Xiaohong Wang publishes landmark paper “Bioartificial Organ Manufacturing Technologies”

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Xiaohong Wang publishes landmark paper “Bioartificial Organ Manufacturing Technologies”

June 07
08:36 2019

The latest research paper titled, “Bioartificial Organ Manufacturing Technologies” is written by Xiaohong Wang and attempts to review the progress in organ intelligent three-dimensional (3D) printing and other manufacturing technologies. Xiaohong Wang is the Founder and Director of both the School of Fundamental Sciences, China Medical University (CMU), and the Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University (Figure 1).

Organ failure is one of the leading causes of mortality ailing humans worldwide. Despite advances being made in interventional, pharmacological and surgical therapies yet there has not been a significant dip in the numbers of people dying due to organ failure. At present, orthotopic organ transplantation is the only way to expand the life span of humans. However, this method has its own shortcomings viz., high price, immune rejection, donor shortage and ethical conflict.

To put it more simply, an artificial organ is an engineered device that can be implanted or integrated into a human body interfacing with living tissue. This replaces a natural organ, to emulate or augment a specific function or functions to aid in faster recovery of the patient allowing him/her to return to normal life.

It has been observed that according to the materials used, artificial organs can be classified into three main classes. The first one being mechanical, the second one being biomechanical and the third one is biological. Wang describes that normally the former two classes help in only partially and temporary replacement and repair of the failed organs whereas the biological class could permanently restore the defective/failed organs.

In this research study conducted by Professor Wang, only biological (or bioartificial) organ manufacturing technologies are reviewed. According to Wang, the simplest and most direct approach to bioartificial organ manufacturing is to mimic the original counterpart with respect to structures (including primary anatomical architectures), components (including multiple cell types, supportive biomaterials and bioactive agents)  and functions (including physiological and pathological functionalities). Hence, Wang suggests that building a bioartificial organ requires precise control and a detailed understanding of the human body’s fundamental intricate responses to all environmental factors, especially to the implanted biomaterials.

Bioartificial organ manufacturing is an interdisciplinary field that has close inter-relationships with many modern sciences and technologies. Professor Wang’s research showed that advanced technologies for heterogeneous cell/extracellular matrix/growth factor assembly are essential for the successful manufacturing of large scale-up implantable human organs.

In addition to the above, Professor Wang’s findings showed that different organs need different biomaterials and manufacturing technologies. The establishment of a large scaled-up hierarchical vascular network is vital to consistently supply with living cells with nutrients and oxygen to maintain their survival and metabolic function for most of the solid organs. Particularly, post culture is another essential factor for homogeneous/heterogeneous tissue formation, maturation, and coordination in a physiological functional organ substitute. It was also observed that one of the most promising bioartificial organ manufacturing technologies is to use combined multi-nozzle 3D printing techniques, that Professor Wang  has applied for more than 60 international or national patents, and published more than 130 articles; most of them are in the list of Science Citation Index (SCI) (one in Trends inBiotechnologies, impact factor: 13.578, six in Biomaterials, impact factor: 8.806). She is also the author of the book “Organ Manufacturing” published in the US in 2015. With these advanced biotechnologies or high-technologies, Professor Wang has solved all the bottleneck problems perplexed tissue engineers for more than three decades (Figure 2, 3). Undoubtedly, these advanced biotechnologies will significantly improve the quality of human life and prolong the average life-span of human beings.

The combination of advanced technologies has made it possible to construct (or develop) physiologically functional bioartificial organs, such as the vascularized and innervated bioartificial livers. The research by Professor Wang comes at a time when organ failure is extremely common worldwide. This is why it is essential to study organ-manufacturing technologies as they hold the promise to change the destiny of human beings in the near future. Professor Wang has certainly proved her intellect by analysing and establishing a brand new complex field. Like a shining beacon in the dead night, her outstanding research will bring solutions and save humans.

Figure 1. A photo of Professor Xiaohong Wang

Figure 2. A schematic description of several pioneered three-dimensional (3D) bioprinters made in Tsinghua Unversity, Prof. Wang’ laboratory: (A) a single-nozzle 3D bioprinter with large scale-up living tissues in 2004; (B) two cell types in the gelatin-based hydrogels were printed simultaneously into large scale-up organs in 2007; (C) both cell containing natural gelatin-based hydrogel and synthetic polymer systems were printed into large scale-up vascularized tissues with a hierarchical vascular network using the home-made double-nozzle low-temperature deposition manufacturing (DLDM) device (i.e. DLDM 3D bioprinter) in 2009. An ellipticalhybrid hierarchical polyurethane and cell/hydrogel construct was produced using the DLDM 3D bioprinter; (D) modeling and manufacturing four bioartificial livers using a four-nozzle low-temperature 3D bioprinter in 2010. 

Figure 3. A combined four-nozzle organ three-dimensional (3D) bioprinting technology created  in Tsinghua Unversity, Prof. Wang’ laboratory in 2013: (A) equipment of the combined four-nozzle organ 3D bioprinter; (B) working state of the combined four-nozzle organ 3D printer; (C) a computer aided design (CAD) model representing a large scale-up vascularized and innervated hepatic tissue; (D) a semi-ellipse 3D construct containing a poly (lactic acid-co-glycolic acid) (PLGA) overcoat, a hepatic tissue (made from hepatocytes in the gelatin/chitosan hydrogel), a branched vascular network (with a fully confluent endothelialized adipose-derived stem cells (ASCs) on the inner surface of the gelatin/alginate/fibrin hydrogel) and a hierarchical nervous (or innervated) network (made from Shwann cells in the gelatin/hyaluronate hydrogel), the maximal diameter of the semi-ellipse can be adjusted from 1 mm to 2 cm according to the CAD model; (E) a cross section of (D), showing the endothelialized ASCs and Schwann cells around a branched channel; (F) a large bundle of nerve fibers formed in (D);  (G) hepatocytes underneath the PLGA overcoat;  (H) an interface between the endothelialized ASCs and Schwann cells in (D); (I) some thin nerve fibers.

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