Can Human Organs Be Manufactured or Replicated for Crisis Situations? Can We Extend Human Lifespan?

The possibility of manufacturing or replicating human organs presents a groundbreaking opportunity to address one of the most pressing health crises: organ failure. Despite significant advancements in interventional, pharmacological, and surgical therapies, organ failure remains a leading cause of mortality worldwide. Traditional methods like orthotopic organ transplantation, while effective, face severe limitations, including donor shortages, high costs, immune rejection, and ethical issues. However, recent developments in bioartificial organ manufacturing offer a promising alternative that could revolutionize healthcare and significantly extend human lifespans.

The Dream of Bioartificial Organ Manufacturing

The concept of bioartificial organ manufacturing has been a long-term dream, pursued throughout history by various means to substitute or restore defective organs. Modern technology has brought us closer than ever to realizing this dream. Advanced material processing technologies such as multi-nozzle rapid prototyping (MNRP), additive combined molding, decellularized matrix regeneration, electrophoresis, and magnetic adsorption of cells are making the creation of bioartificial organs increasingly feasible.

These technologies integrate heterogeneous cell types and multiple materials to mimic the geometry, constituents, and functions of native organs. The challenge lies in assembling these living cells into predesigned architectures that include hierarchical vascular, neural, and lymphatic networks, while ensuring the functionality of these structures.

Types of Artificial Organs

Artificial organs can be classified into three main categories based on the materials used:

1. Mechanical: Made of inanimate polymers and/or metals.
2. Biomechanical: Comprised of partially living cells combined with polymers and/or metals.
3. Biological (Bioartificial): Constructed from living cells, biodegradable polymers, and metal elements.

Mechanical and biomechanical organs can only temporarily and partially replace failed organs, while bioartificial organs have the potential to completely and permanently restore the function of defective organs. This makes the development of bioartificial organs particularly exciting.

Definition and Scope of Organ Manufacturing

Organ manufacturing is defined as producing bioartificial organs using living cells (e.g., adult cells, stem cells) and other biomaterials (e.g., polymers, growth factors, bioactive agents), alongside advanced processing technologies. This interdisciplinary field encompasses biology, materials science, chemistry, physics, informatics, mechanics, computing, surgery, and medicine. The goal is to produce organs that can integrate with human tissues and restore organ function, much like natural counterparts.

Advances and Challenges

Since the establishment of the Center of Organ Manufacturing at Tsinghua University in 2003, there have been significant advancements in this field. Technologies such as 3D bioprinting have enabled the creation of vascularized tissues and complex organ structures. For instance, various 3D bioprinters have successfully printed hepatocytes, adipose-derived stem cells, and large-scale vascularized organs.

Despite these advancements, numerous challenges remain. Organ manufacturing requires precise control over multiple cell types and materials, as well as a detailed understanding of the human body’s response to these bioartificial constructs. Ensuring the functionality of these organs and their integration into the human body is complex and requires further research and development.

Extending Human Lifespan

The ability to manufacture organs on demand could drastically reduce mortality rates associated with organ failure. Additionally, it holds the potential to extend human lifespan by providing solutions to age-related organ degradation. By replacing or repairing defective organs, we could improve the quality of life for aging populations and extend the healthy, functional years of individuals.

The manufacturing of bioartificial organs represents a revolutionary advancement in medical science. While challenges remain, the progress in this field offers hope for addressing organ failure crises and potentially extending human lifespans. As technology continues to evolve, the dream of creating fully functional bioartificial organs may soon become a reality, transforming healthcare and enhancing the quality of life for millions around the world.

Pioneering the Future: The Uncharted Territory of Intelligent 3D Printing in Organ Manufacturing

The realm of 3D printing has evolved dramatically, transcending the boundaries of traditional manufacturing and entering the intricate field of organ manufacturing. This advanced technology, often referred to as bioprinting, leverages rapid prototyping techniques and a diverse range of biomaterials to construct complex, functional organ analogues. Researchers like Wang and colleagues have been at the forefront, exploring how to integrate intelligent systems for the precise and scalable creation of organs . The potential of 3D printing to create bioartificial livers and other vital organs presents a revolutionary approach to addressing the critical shortages in organ transplants .

In particular, the development of vascular systems within these printed organs is a key advancement, ensuring that these constructs can sustain the necessary blood flow and nutrient delivery to maintain cell viability . This innovative approach not only offers hope for patients awaiting transplants but also paves the way for more personalized and efficient treatments. As the field progresses, the integration of stem cells, biodegradable polymers, and intelligent scaffolds continues to enhance the functionality and biocompatibility of these printed organs . The future of medicine is being reshaped by these groundbreaking technologies, promising a new era where organ shortages are a relic of the past, and personalized medicine is the norm.

References

1. Liu L, Wang X. Organ manufacturing. In: Wang X.H., editor. Organ Manufacturing Hauppauge (NY): Nova Science Publishers Inc.; 2015;1–28. [Google Scholar]

2. Wang X, Tuomi J, Mäkitie AA, Poloheimo K-S, Partanen J, Yliperttula M. The integrations of biomaterials and rapid prototyping techniques for intelligent manufacturing of complex organs In: Lazinica R, editor. Advances in Biomaterials Science and Applications in Biomedicine. Rijeka, Croatia: InTech; 2013;437–463. [Google Scholar]

3. Wang X, Yan Y, Zhang R. Rapid prototyping as tool for manufacturing bioartificial livers. Trends Biotechnol. 2007;25(11):505–513. [PubMed] [Google Scholar]

4. Wang X, Yan Y, Zhang R. Recent trends and challenges in complex organ manufacturing. Tissue Eng Part B Rev. 2010;16(2):189–197. [PubMed] [Google Scholar]

5. Wang X. Intelligent free form manufacturing of complex organs. Artif Organs. 2012;36(11):951–961. [PubMed] [Google Scholar]

6. Liu L, Wang X. Creation of a vascular system for complex organ manufacturing. Int J Bioprinting. 2015;1(1):77–86. [Google Scholar]

7. Aikawa E, Nahrendorf M, Sosnovik D, Lok VM, Jaffer FA, Aikawa M, Weissleder R. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation. 2007;115(3):377–386. [PubMed] [Google Scholar]

8. Moniaux N, Faivre JA. A reengineered liver for transplantation. J Hepatol. 2011;54(2):386–387. [PubMed] [Google Scholar]

9. Orive G, Hernández RM, Gascón AR. History, challenges and perspectives of cell microencapsulation. Trends Biotechnol. 2004;22(2):87–92. [PubMed] [Google Scholar]

10. Derby B. Printing and prototyping of tissues and scaffolds. Science. 2012;338(6109):921–926. [PubMed] [Google Scholar]

11. Guillotin B, Guillemot F. Cell patterning technologies for organotypic tissue fabrication. Trends Biotechnol. 2011;29(4):183–190. [PubMed] [Google Scholar]

12. Durmus NG, Tasoglu S, Demirci U. Bioprinting: functional droplet networks. Nat Mater. 2013;12(6):478–479. [PubMed] [Google Scholar]

13. Padalino MA, Speggiorin S, Rizzoli G, Crupi G, Vida VL, Bernabei M, Gargiulo G, Giamberti A, Santoro F, Vosa C, Pacileo G, Calabrò R, Daliento L, Stellin G. Midterm results of surgical intervention for congenital heart disease in adults: an Italian multicenter study. J Thorac Cardiovasc Sur. 2007;13 4(1):106–113. [PubMed] [Google Scholar]

14. Myers TJ, Bolmers M, Gregoric ID, Kar B, Frazier OH. Assessment of arterial blood pressure during support with an axial flow left ventricular assist device. J Heart Lung Transplant. 2009;28(5):423–427. [PubMed] [Google Scholar]

15. Copeland JG, Smith RG, Arabia FA. Cardiac replacement with a total artificial heart as a bridge to transplantation. N Engl J Med. 2004;351(9):859–867. [PubMed] [Google Scholar]

16. Catapano G, Verkerke GJ. Chapter 2: Artificial organs. In: Abu-Faraj ZO, editor. Handbook of research on biomedical engineering education and advanced bioengineering learning: interdisciplinary concepts. Hershey, PA: Medical Information Science Reference; 2012:60–95. ISBN 9781466601239. [Google Scholar]

17. Industrial System Research. Manufacturing and investment around the world: an international survey of factors affecting growth and performance, 2nd ed Manchester, UK: ISR Publications/Google Books; 2002. ISBN 978-0-906321-25-6. [Google Scholar]

18. Groover MP. Metal casting processes In: Groover MP, editor. Fundamentals of modern manufacturing, materials, processes and systems 4th ed Hoboken, NJ: John Wiley & Sons; 2010:225–257. [Google Scholar]

19. Wang X. 3D printing of tissue/organ analogues for regenerative medicine In: Gilson K, editor. Handbook of Intelligent Scaffolds for Regenerative Medicine. 2nd ed Pan Stanford Publishing: Palo Alto, CA, USA; 2017;557–570. [Google Scholar]

20. Wang X, Ao Q, Tian X, Fan J, Wei Y, Tong H, Hou W, Bai S. Gelatin-based hydrogels for organ 3D bioprinting. Polymers. 2017;9(9):401. [PMC free article] [PubMed] [Google Scholar]

21. Lei M, Wang X. Biodegradable polymers and stem cells for bioprinting. Molecules. 2016;21(5):539. [PMC free article] [PubMed] [Google Scholar]

22. Wang X. Overview on biocompatibilities of implantable biomaterials In: Lazinica R, editor. Advances in Biomaterials Science and Biomedical Applications in Biomedicine. InTech: Rijeka Croatia; 2013;111–155. [Google Scholar]

23. Yan Y, Wang X, Pan Y, Liu H, Cheng J, Xiong Z, Lin F, Wu R, Zhang R, Lu Q. Fabrication of viable tissue-engineered constructs with 3D cell-assembly technique. Biomaterials. 2005;26(29):5864–5871. [PubMed] [Google Scholar]

24. Li S, Xiong Z, Wang X, Yan Y, Liu H, Zhang R. Direct fabrication of a hybrid cell/hydrogel construct via a double-nozzle assembling technology. J Bioact Compat Polym. 2009;24(3):249–264. [Google Scholar]

25. Xu W, Wang X, Yan Y, Zhang R. A polyurethane-gelatin hybrid construct for the manufacturing of implantable bioartificial livers. J Bioact Compat Polym. 2008;23(5):409–422. [Google Scholar]

26. Huang Y, He K, Wang X. Rapid Prototyping of a hybrid hierarchical polyurethane-cell/hydrogel construct for regenerative medicine. Mater Sci Eng C. 2013;33(6):3220–3229. [PubMed] [Google Scholar]

27. Wang X, Huang Y, Liu C. A combined rotational mold for manufacturing a functional liver system. J Bioact Compat Polym. 2015;30(4):436–451. [Google Scholar]

28. Wang X, Yan Y, Lin F, Xiong Z, Wu R, Zhang R, Lu Q. Preparation and characterization of a collagen/chitosan/heparin matrix for an implantable bioartificial liver. J Biomat Sci Polym E. 2005;16(9):1063–1080. [PubMed] [Google Scholar]

29. Wang X, Li D, Wang W, Feng Q, Cui F, Xu Y, Song X, van der Werf M. Crosslinked collagen/chitosan matrices for artificial livers. Biomaterials. 2003;24(19):3213–3220. [PubMed] [Google Scholar]

30. Xu M, Yan Y, Liu H, Yao Y, Wang X. Control adipose-derived stromal cells differentiation into adipose and endothelial cells in a 3-D structure established by cell-assembly technique. J Bioact Compat Polym. 2009;24(S1):31–47. [Google Scholar]

31. Xu M, Wang X, Yan Y, Yao R, Ge Y. A cell-assembly derived physiological 3D model of the metabolic syndrome, based on adipose-derived stromal cells and a gelatin/alginate/fibrinogen matrix. Biomaterials. 2010;31(14):3868–3877. [PubMed] [Google Scholar]

32. Wang J, Wang X. Vascularization and adipogenesis of a spindle hierarchical adipose-derived stem cell/collagen/ alginate-PLGA construct for breast manufacturing. IJITEE. 2015;4(8):1–8. [Google Scholar]

33. Wang X. Spatial effects of stem cell engagement in 3D printing constructs. J Stem Cells Res Rev Rep. 2014;1(2):5–9. [Google Scholar]

34. Wang X. Editorial: drug delivery design for regenerative medicine. Curr Pharm Des. 2015;21(12):1503–1505. [PubMed] [Google Scholar]

35. Wang J. Development of a combined 3D printer and its application in complex organ construction. Master’s Thesis, Tsinghua University, Beijing, China, 2014. [Google Scholar]

36. Zhao X, Liu L, Wang J, Xu Y, Zhang W, Khang G, Wang X. In vitro vascularization of a combined system based on a 3D printing technique. J Tissue Eng Regen Med. 2016;10(10):833–842. [PubMed] [Google Scholar]

37. Zhao X, Du S, Chai L, Zhou X, Liu L, Xu Y, Wang J, Zhang W, Liu C-H, Wang X. Anti-cancer drug screening based on an adipose-derived stem cell/hepatocye 3D printing technique. J Stem Cell Res Ther. 2015;5:273. [Google Scholar]

38. Zhou X, Wang X. 3D bioprinting liver tumor model for drug screening. World J Pharm Sci. 2016;5(4):196–213. [Google Scholar]

39. Berillis P. The role of collagen in the aorta’s structure. Open Circ Vasc J. 2013;6:1–8. [Google Scholar]

40. ISO/TC 261; ASTM F42. ISO/ASTM 52900:2015(en) Additive Manufacturing–General principles–Terminology; Geneva, Switzerland: ISO/ASME International: 2015. [Google Scholar]

41. Ozbolat IT. Bioprinting scale-up tissue and organ constructs for transplantation. Trends Biotechnol. 2015;33(7):1–6. [PubMed] [Google Scholar]

42. Pati F, Jang J, Ha D-H, Won Kim S, Rhie J-W, Cho DW. Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun. 2014;5:1–11. [PMC free article] [PubMed] [Google Scholar]

43. Akmal JS, Salmi M, Mäkitie A, Björkstrand R, Partanen J. Implementation of industrial additive manufacturing: intelligent implants and drug delivery systems. J Funct Biomater. 2018;9(3):41. [PMC free article] [PubMed] [Google Scholar]

44. Mäkitie AA, Salmi M, Lindford A, Tuomi J, Lassus P. Three-dimensional printing for restoration of the donor face: a new digital technique tested and used in the first facial allotransplantation patient in Finland. J Plast Reconstr Aesthet Surg. 2016;69(12):1648–1652. [PubMed] [Google Scholar]

45. Tuomi JT, Björkstrand RV, Pernu ML, Salmi MVJ, Huotilainen EI, Wolff JEH, Vallittu PK, Mäkitie AA. In vitro cytotoxicity and surface topography evaluation of additive manufacturing titanium implant materials. J Mater Sci Mater Med. 2017;28(3):53. [PubMed] [Google Scholar]

46. Salmi M. Possibilities of preoperative medical models made by 3D printing or additive manufacturing. J Med Eng. 2016;2016:6191526. [PMC free article] [PubMed] [Google Scholar]

47. Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, Chen M, He Q, Liao Y, Yu X, Chen N, Zhang J, Hu Z, Liu F, Hong D, Ma L, Liu H, Zhou X, Chen J, Pan L, Chen W, et al. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet. 2012;379(9818):815–822. [PubMed] [Google Scholar]

48. Huang H, Sharma HS. Neurorestoratology: one of the most promising new disciplines at the forefront of neuroscience and medicine. J Neurorestoratol. 2013;1:37–41. [Google Scholar]

49. Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology. 2011;53(2):604–617. [PubMed] [Google Scholar]

50. Crapo PM, Gilbert TW, Badylak S. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011;32(12):3233–3243. [PMC free article] [PubMed] [Google Scholar]

51. Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis J. 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater. 2014;26(19):3124–3130. [PubMed] [Google Scholar]

52. Yu Y, Zhang Y, Ozbolat IT. A hybrid bioprinting approach for scale-up tissue fabrication. J Manuf Sci Eng. 2014;136(6):1–6. DOI: 10.1115/1.4028511. [Google Scholar]

53. Sahota PS, Burn J L, Heaton M, Freedlander E, Suvarna SK, Brown NJ, Mac Neil S. Development of a reconstructed human skin model for angiogenesis. Wound Repair Regen. 2003;11(4):275–284. [PubMed] [Google Scholar]

54. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotech. 2014;32(8):773–785. [PubMed] [Google Scholar]

55. Vert M, Doi Y, Hellwich K-H, Hess M, Hodge P, Kubisa P, Rinaudo M, Schué F. Terminology for biorelated polymers and applications (IUPAC Recommendations 2012). Pure Appl Chem. 2012;84(2):377–410. [Google Scholar]

56. Gou M, Qu X, Zhu W, Xiang M, Yang J, Zhang K, Wei Y, Chen S. Bio-inspired detoxification using 3D-printed hydrogel nanocomposites. Nat Commun. 2014;5:3774. [PMC free article] [PubMed] [Google Scholar]

57. Ott HC, Matthiesen TS, Goh S-K, Black LD, Kren SM, Netoff TI, Taylor DA. Perfusion decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14(2):213–221. [PubMed] [Google Scholar]

58. Murry C E, Keller G. Differentiation of embryonic stem cells to clinically relevant populations: lessons from embryonic development. Cell. 2008;132(4):661–680. [PubMed] [Google Scholar]

59. Lu T-Y, Lin B, Kim J, Sullivan M, Tobita K, Salama G, Yang L. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nat Commun. 2013;4:2307. [PubMed] [Google Scholar]

60. Uygun BE, Soto-Gutierrez A, Yagi H, Izamis M-L, Guzzardi M, Shulman C, Milwid J, Kobayashi N, Tilles A, Berthiaume F, Hert M, Nahmias Y, Yarmush ML, Uygun K. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med. 2010;16(7):814–820. [PMC free article] [PubMed] [Google Scholar]

61. Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC. Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med. 2013;19(5):646–651. [PMC free article] [PubMed] [Google Scholar]

62. Benders KEM, Van Weeren PR, Badylak SF, Saris DBF, Dhert WJ, Malda J. Extracellular matrix scaffolds for cartilage and bone regeneration. Trends Biotechnol. 2013;31(3):169–176. [PubMed] [Google Scholar]

63. Dvir T, Timko BP, Brigham MD, Naik SR, Karajanagi SS, Levy O, Jin H, Parker KK, Langer R, Kohane DS. Nanowired three-dimensional cardiac patches. Nat Nanotechnol. 2011;6(11):720–725. [PMC free article] [PubMed] [Google Scholar]

64. Xu L, Gutbrod SR, Bonifas AP, Su Y, Sulkin MS, Lu N, Chung H-J, Jang K-I, Liu Z, Ying M, Lu C, Webb R C, Kim J-S, Laughner JI, Cheng H, Liu Y, Ameen A, Jeong J-W, Kim G-T, Huang Y, Efimov IR, Rogers JA. 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium. Nat Commun. 2014;5:3329. [PMC free article] [PubMed] [Google Scholar]

65. Shimizu T. Cell sheet-based tissue engineering for fabricating 3-dimensional heart tissues. Circ J. 2014;78(11):2594–2603. [PubMed] [Google Scholar]

66. Fritzsch B. Electric organs: history and potential. Science. 2014;345(6197):631–632. [PubMed] [Google Scholar]

67. Mannoor MS, Jiang Z, James T, Kong YL, Malatesta KA, Soboyejo WO, Verma N, Gracias DH, McAlpine MC. 3D printed bionic ears. Nano Lett. 2013;13(6):2634–2639. [PMC free article] [PubMed] [Google Scholar]

68. Gallant JR, Traeger LL, Volkening JD, Moffett H, Chen P-H, Novina CD, Phillips GN, Jr, Anand R, Wells GB, Pinch M, Güth R, Unguez GA, Albert JS, Zakon HH, Samanta MP, Sussman MR. Genomic basis for the convergent evolution of electric organs. Science. 2014;344(6191):1522–1525. [PMC free article] [PubMed] [Google Scholar]