3D Bioprinting of Adipose-Derived Stem Cells for Organ Manufacturing

  • Xiaohong WangEmail author
  • Chang Liu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1078)


Organ manufacturing is an attractive high-tech research field which can solve the serious donor shortage problems for allograft organ transplantation, high throughput drug screening, and energy metabolism model establishment. How to integrate heterogeneous cell types along with other biomaterials to form bioartificial organs is one of the kernel issues for organ manufacturing. At present, three-dimensional (3D) bioprinting of adipose-derives stem cell (ADSC) containing hydrogels has shown the most bright futures with respect to overcoming all the difficult problems encountered by tissue engineers over the last several decades. In this chapter, we briefly introduce the 3D ADSC bioprinting technologies for organ manufacturing, especially for the branched vascular network construction.


Organ manufacturing Three-dimensional (3D) bioprintng Rapid prototyping Tissue engineering Biomaterials Stem cells 



The work was supported by grants from the National Natural Science Foundation of China (NSFC) (No. 81571832 & 81271665), the 2017 Discipline Promotion Project of China Medical University (CMU) (No. 3110117049), and the International Cooperation and Exchanges NSFC and Japanese Society for the Promotion of Science (JSPS) (No. 81411140040).


  1. 1.
    Wang X, Yan Y, Lin F, Xiong Z, Wu R, Zhang R, Lu Q (2005) Preparation and characterization of a collagen/chitosan/heparin matrix for an implantable bioartificial liver. J Biomater Sci Polym Ed 16:1063–1080CrossRefGoogle Scholar
  2. 2.
    Wang X, Yan Y, Zhang R (2007) Rapid prototyping as tool for manufacturing bioartificial livers. Trends Biotechnol 25:505–513CrossRefGoogle Scholar
  3. 3.
    Wang X, Yan Y, Zhang R (2016) Recent trends and challenges in complex organ manufacturing. Tissue Eng Part B 16:189–197CrossRefGoogle Scholar
  4. 4.
    Wang X (2012) Intelligent freeform manufacturing of complex organs. Artif Org 36:951–961CrossRefGoogle Scholar
  5. 5.
    Wang X, Huang Y, Liu CA (2015) Combined rotational mold for manufacturing a functional liver system. J Bioact Compat Polym 39:436–451CrossRefGoogle Scholar
  6. 6.
    Lei M, Wang X (2016) Biodegradable polymers and stem cells for bioprinting. Molecules 21:539CrossRefGoogle Scholar
  7. 7.
    Wang X, Yan Y, Pan Y, Xiong Z, Liu H, Cheng J, Liu F, Lin F, Wu R, Zhang R, Lu Q (2006) Generation of three-dimensional hepatocyte/gelatin structures with rapid prototyping system. Tissue Eng 12:83–90CrossRefGoogle Scholar
  8. 8.
    Yan Y, Wang X, Pan Y, Liu H, Cheng J, Xiong Z, Lin F, Wu R, Zhang R, Lu Q (2005) Fabrication of viable tissue-engineered constructs with 3D cell-assembly technique. Biomaterials 26:5864–5871CrossRefGoogle Scholar
  9. 9.
    Xu W, Wang X, Yan Y, Zheng W, Xiong Z, Lin F, Wu R, Zhang R (2007) Rapid prototyping three-dimensional cell/gelatin/fibrinogen constructs for medical regeneration. J Bioact Compat Polym 22:363–377CrossRefGoogle Scholar
  10. 10.
    Zhang T, Yan Y, Wang X, Xiong Z, Lin F, Wu R, Zhang R (2007) Three-dimensional gelatin and gelatin/hyaluronan hydrogel structures for traumatic brain injury. J Bioact Compat Polym 22:19–29CrossRefGoogle Scholar
  11. 11.
    Wang X, Ao Q, Tian X, Fan J, Wei Y, Tong H, Hou W, Bai S (2017) Gelatin-based hydrogels for organ 3D bioprinting. Polymers 9:401. CrossRefGoogle Scholar
  12. 12.
    Wang X, Ao Q, Tian X, Fan J, Wei Y, Hou W, Tong H, Bai S (2016) 3D bioprinting technologies for hard tissue and organ engineering. Materials 9:802. CrossRefPubMedCentralGoogle Scholar
  13. 13.
    Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926CrossRefGoogle Scholar
  14. 14.
    Moniaux N, Faivre JA (2011) Reengineered liver for transplantation. J Hepatol 54:386–387CrossRefGoogle Scholar
  15. 15.
    Mironov V, Boland T, Trusk T, Forgacs G, Markwald RR (2003) Organ printing: computer-aided jet-based 3D tissue engineering. Trends Biotechnol 21:157–161CrossRefGoogle Scholar
  16. 16.
    Xu Y, Li D, Wang X (2015) Current trends and challenges for producing artificial hearts. In: Wang XH (ed) Organ manufacturing. Nova Science Publishers Inc, New York, pp 101–125Google Scholar
  17. 17.
    Zhou X, Wang X (2015) Artificial kidney manufacturing. In: Wang X (ed) Organ manufacturing. Nova Science Publishers Inc, New York, pp 227–244Google Scholar
  18. 18.
    Xu Y, Li D, Wang X (2015) The construction of vascularized pancreas based on 3D printing techniques. In: Wang X (ed) Organ manufacturing. Nova Science Publishers Inc, New York, pp 245–268Google Scholar
  19. 19.
    Wang X, Wang J (2015) Vascularization and adipogenesis of a spindle hierarchical adipose-derived stem cell/collagen/alginate-PLGA construct for breast manufacturing. International Journal of Innovative Technology and Exploring Engineering (IJITEE) 4:1–8Google Scholar
  20. 20.
    Wang X (2015) Editorial: drug delivery design for regenerative medicine. Curr Pharm Des 21(12):1503–1505CrossRefGoogle Scholar
  21. 21.
    Libiao Liu WX (2015) Creation of a vascular system for complex organ manufacturing. Int J Bioprinting 1:77–86Google Scholar
  22. 22.
    Zhao X, Du S, Chai L, Zhou X, Liu L, Xu Y, Wang J, Zhang W, Liu C-H, Wang X (2015) Anti-cancer drug screening based on an adipose-derived stem cell/hepatocye 3D printing technique. J Stem Cell Res Ther 5:273. CrossRefGoogle Scholar
  23. 23.
    Chua CK, Yeong WY (2015) Bioprinting: principles and Applications. World Scientific Publishing Co., Singapore, p 296. isbn:9789814612104 Google Scholar
  24. 24.
    Hendriks J, Willem Visser C, Henke S, Leijten J, Saris DB, Sun C, Lohse D, Karperien M (2015) Optimizing cell viability in droplet-based cell deposition. Sci Rep 11:11304CrossRefGoogle Scholar
  25. 25.
    Cui X, Dean D, Ruggeri ZM, Boland T (2010) Cell damage evaluation of thermal inkjet printed Chinese hamster ovary cells. Biotechnol Bioeng 106:963–969CrossRefGoogle Scholar
  26. 26.
    Singh M, Haverinen HM, Dhagat P, Jabbour GE (2010) Inkjet printing-process and its applications. Adv Mater 22:673–685CrossRefGoogle Scholar
  27. 27.
    Irvine SA, Venkatraman SS (2016) Bioprinting and differentiation of stem cells. Molecules 21:E1188CrossRefGoogle Scholar
  28. 28.
    Panwar A, Tan LP (2016) Current status of bioinks for micro-extrusion-based 3D bioprinting. Molecules 21:E685CrossRefGoogle Scholar
  29. 29.
    Ozbolat IT, Hospodiuk M (2016) Current advances and future perspectives in extrusion-based bioprinting. Biomaterials 76:321–343CrossRefGoogle Scholar
  30. 30.
    Kolesky DB, Truby RL, Gladman AS, Busbee TA, Homan KA, Lewis JA (2014) Bioprinting: 3D bioprinting of vascularized, heterogeneous cell-laden tissue constructs. Adv Mater 26:3124–3130CrossRefGoogle Scholar
  31. 31.
    Jia W, Gungor-Ozkerim PS, Zhang YS, K Y, Zhu K, Liu W, Pi Q, Byambaa B, Dokmeci MR, Shin SR, Khademhosseini A (2016) Direct 3D bioprinting of perfusable vascular constructs using a blend bioink. Biomaterials 106:58–68CrossRefGoogle Scholar
  32. 32.
    Saunders RE, Gough JE, Derby B (2008) Delivery of human fibroblast cells by piezoelectric drop-on-demand inkjet printing. Biomaterials 29:193–203CrossRefGoogle Scholar
  33. 33.
    Guillotin B, Souquet A, Catros S, Duocastella M, Pippenger B, Bellance S, Bareille R, Rémy M, Bordenave L, Amédée J, Guillemot F (2010) Laser assisted bioprinting of engineered tissue with high cell density and microscale organization. Biomaterials 31:7250–7256CrossRefGoogle Scholar
  34. 34.
    Gruene M, Pflaum M, Hess C, Diamantouros S, Schlie S, Deiwick A, Koch L, Wilhelmi M, Jockenhoevel S, Haverich A, Chichkov B (2011) Laser printing of three-dimensional multicellular arrays for studies of cell-cell and cell-environment interactions. Tissue Eng Part C Methods 17:973–982CrossRefGoogle Scholar
  35. 35.
    Guillemot F, Souquet A, Catros S, Guillotin B, Lopez J, Faucon M, Pippenger B, Bareille R, Rémy M, Bellance S, Chabassier P, Fricain JC, Amédée J (2010) High-throughput laser printing of cells and biomaterials for tissue engineering. Acta Biomater 6:2494–2500CrossRefGoogle Scholar
  36. 36.
    Billiet T, Vandenhaute M, Schelfhout J, Van Vlierberghe S, Dubruel P (2012) A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials 33(26):6020–6041CrossRefGoogle Scholar
  37. 37.
    Liu L, Wang X (2015) Hared tissue and organ manufacturing. In: Wang X (ed) Organ manufacturing. Nova Science Publishers Inc, New York, pp 301–333Google Scholar
  38. 38.
    Kim JD, Choi JS, Kim BS et al (2010) Piezoelectric inkjet printing of polymers: stem cell patterning on polymer substrates. Polymer 51:2147–2154CrossRefGoogle Scholar
  39. 39.
    Loo Y, Hauser CA (2015) Bioprinting synthetic self-assembling peptide hydrogels for biomedical applications. Biomed Mater 11:014103CrossRefGoogle Scholar
  40. 40.
    Matias JM, Bartolo PJ, Pontes AV (2009) Modeling and simulation of photofabrication processes using unsaturated polyester resins. J Appl Polym Sci 114:3673–3685CrossRefGoogle Scholar
  41. 41.
    Arcaute K, Mann BK, Wicker RB (2006) Stereolithography of three-dimensional bioative poly(ethylene glycol) constructs with encapsulated cells. Ann Biomed Eng 34:1429–1441CrossRefGoogle Scholar
  42. 42.
    Ng WL, Yeong WY, Naing MW (2017) Polyvinylpyrrolidone-based bio-ink improves cell viability and homogeneity during drop-on-demand printing. Materials 10:190CrossRefGoogle Scholar
  43. 43.
    Kouhi E, Masood S, Morsi Y (2008) Design and fabrication of reconstructive mandibular models using fused deposition modeling. Assem Autom 28:246–254CrossRefGoogle Scholar
  44. 44.
    Ricci JL, Clark EA, Murriky A, Smay JE (2012) Three-dimensional printing of bone repair and replacement materials: impact on craniofacial surgery. J Craniofac Surg 23:304–308CrossRefGoogle Scholar
  45. 45.
    Xue W, Krishna BV, Bandyopadhyay A, Bose S (2007) Processing and biocompatibility evaluation of laser processed porous titanium. Acta Biomater 3:1007–1018CrossRefGoogle Scholar
  46. 46.
    Wang X. (2014) 3D printing of tissue/organ analogues for regenerative medicine, In: Handbook of intelligent Scaffolds for regenerative medicine, G Khang ed, the 2nd, Singapore Pan Stanford Publishing pp.557–570Google Scholar
  47. 47.
    Chi W-J, Chang Y-K, Hong S-K (2012) Agar degradation by microorganisms and agar-degrading enzymes. Appl Microbiol Biotechnol 94:917–930CrossRefGoogle Scholar
  48. 48.
    Zhang L-M, Wu C-X, Huang J-Y, Peng X-H, Chen P, Tang S-Q (2012) Synthesis and characterization of a degradable composite agarose/HA hydrogel. Carbohydr Polym 88:1445–1452CrossRefGoogle Scholar
  49. 49.
    Xu Y, Wang X (2015) Application of 3D biomimetic models for drug delivery and regenerative medicine. Curr Pharm Des 21:1618–1626CrossRefGoogle Scholar
  50. 50.
    Liu L, Zhou X, Xu Y, Zhang W, Liu C-H, Wang X (2015) Controlled release of growth factors for regenerative medicine. Curr Pharm Des 21:1627–1632CrossRefGoogle Scholar
  51. 51.
    Wang J, Wang X (2014) Development of a combined 3D printer and its application in complex organ construction. M. Eng. thesis, Tsinghua University, Beijing, ChinaGoogle Scholar
  52. 52.
    Ma X, Qu X, Zhu W et al (2016) Deterministically patterned biomimetic human iPSC derived hepatic model via rapid 3D bioprinting. PNAS 113:2206–2211CrossRefGoogle Scholar
  53. 53.
    Tricomi BJ, Dias AD, Corr DT (2016) Stem cell bioprinting for applications in regenerative medicine. Ann N Y Acad Sci 1383:115–124CrossRefGoogle Scholar
  54. 54.
    Koch L, Kuhn S, Sorg H et al (2010) Laser printing of skin cells and human stem cells. Tissue Eng Part C Methods 16:847–854CrossRefGoogle Scholar
  55. 55.
    Gu Q, Tomaskovic-Crook E, Lozano R et al (2016) Functional 3D neural mini-tissues from printed gel-based bioink and human neural stem cells. Adv Healthc Mater 5:1429–1438CrossRefGoogle Scholar
  56. 56.
    Hsieh FY, Lin HH, Hsu SH (2015) 3D bioprinting of neural stem cell-laden thermoresponsive biodegradable polyurethane hydrogel and potential in central nervous system repair. Biomaterials 71:48–57CrossRefGoogle Scholar
  57. 57.
    Lee W, Pinckney J, Lee V et al (2009) Three-dimensional bioprinting of rat embryonic neural cells. Neuroreport 20:798–803CrossRefGoogle Scholar
  58. 58.
    Gaebel R, Ma N, Liu J et al (2011) Patterning human stem cells and endothelial cells with laser printing for cardiac regeneration. Biomaterials 32:9218–9230CrossRefGoogle Scholar
  59. 59.
    Skardal A, Mack D, Kapetanovic E et al (2012) Bioprinted amniotic fluid-derived stem cells accelerate healing of large skin wounds. Stem Cells Transl Med 1:792–802CrossRefGoogle Scholar
  60. 60.
    Shi Y, Inoue H, Wu JC, Yamanaka S (2016) Induced pluripotent stem cell technology: a decade of progress. Nat Rev Drug Discov 16:115–130CrossRefGoogle Scholar
  61. 61.
    Phillippi JA, Miller E, Weiss L, Huard J, Waggoner A, Campbell P (2008) Microenvironments engineered by inkjet bioprinting spatially direct adult stem cells toward muscle- and bone-like subpopulations. Stem Cells 26:127CrossRefGoogle Scholar
  62. 62.
    Jung JP, Bhuiyan DB, Ogle BM (2016) Solid organ fabrication: comparison of decellularization to 3D bioprinting. Biomater Res 20:27CrossRefGoogle Scholar
  63. 63.
    Bauwens CL, Peerani R, Niebruegge S et al (2008) Control of human embryonic stem cell colony and aggregate size heterogeneity influences differentiation trajectories. Stem Cells 26:2300–2310CrossRefGoogle Scholar
  64. 64.
    Tasoglu S, Demirci U (2013) Bioprinting for stem cell research. Trends Biotechnol 31:10–19CrossRefGoogle Scholar
  65. 65.
    Hsieh FY, Hsu SH (2015) 3D bioprinting: a new insight into the therapeutic strategy of neural tissue regeneration. Organogenesis 11:153–158CrossRefGoogle Scholar
  66. 66.
    Choi YY, Chung BG, Lee DH, Khademhosseini A, Kim JH, Lee SH (2010) Controlled-size embryoid body formation in concave microwell arrays. Biomaterials 31:4296–4303CrossRefGoogle Scholar
  67. 67.
    Lin X, Shi Y, Cao Y, Liu W (2016) Recent progress in stem cell differentiation directed by material and mechanical cues. Biomed Mater 11:014109CrossRefGoogle Scholar
  68. 68.
    Dimri GP, Lee X, Basile G et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. PNAS 92:9363–9367CrossRefGoogle Scholar
  69. 69.
    Yao R, Zhang R, Yan Y, Wang X (2009) In vitro angiogenesis of 3D tissue engineered adipose tissue. J Bioact Compat Polym 24:5–24CrossRefGoogle Scholar
  70. 70.
    Yao R, Zhang R, Wang X (2009) Design and evaluation of a cell microencapsulating device for cell assembly technology. J Bioact Compat Polym 24:48–62CrossRefGoogle Scholar
  71. 71.
    Xu M, Yan Y, Liu H, Yao Y, Wang X (2009) 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 24:31–47CrossRefGoogle Scholar
  72. 72.
    Xu M, Wang X, Yan Y, Yao R, Ge Y (2010) A cell-assembly derived physiological 3D model of the metabolic syndrome, based on adipose-derived stromal cells and a gelatin/alginate/fibrinogen matrix. Biomaterials 31:3868–3877CrossRefGoogle Scholar
  73. 73.
    Williams SK, Touroo JS, Church KH, Hoying JB (2013) Encapsulation of adipose stromal vascular fraction cells in alginate hydrogel spheroids using a direct-write three-dimensional printing system. Biores Open Access 2:448–454CrossRefGoogle Scholar
  74. 74.
    Ahn SH, Lee HJ, Lee JS, Yoon H, Chun W, Kim GH (2015) A novel cell-printing method and its application to hepatogenic differentiation of human adipose stem cell-embedded mesh structures. Sci Rep 5:13427CrossRefGoogle Scholar
  75. 75.
    Patrick CW Jr (2000) Adipose tissue engineering: the future of breast and soft tissue reconstruction following tumor resection. Semin Sur Oncol 19:302–311CrossRefGoogle Scholar
  76. 76.
    Wang X, Tuomi J, Mäkitie AA, Poloheimo K-S, Partanen J, Yliperttula M (2013) The integrations of biomaterials and rapid prototyping techniques for intelligent manufacturing of complex organs. In: Lazinica R (ed) Advances in biomaterials science and applications in biomedicine. In Tech, Rijeka, pp 437–463Google Scholar
  77. 77.
    Xu Y, Wang X (2015) Fluid and cell behaviors along a 3D printed alginate/gelatin/fibrin channel. Bioeng Biotech 112:1683–1695CrossRefGoogle Scholar
  78. 78.
    Das S, Pati F, Choi YJ, Rijal G, Shim JH, Kim SW, Ray AR, Cho DW, Ghosh S (2015) Bioprintable, cell-laden silk fibroin-gelatin hydrogel supporting multilineage differentiation of stem cells for fabrication of three-dimensional tissue constructs. Acta Biomater 11:233–246CrossRefGoogle Scholar
  79. 79.
    Nickels L (2012) World's first patient-specific jaw implant. Met Powder Rep 67:12CrossRefGoogle Scholar
  80. 80.
    Gaetani R, Doevendans PA, Metz CH et al (2012) Cardiac tissue engineering using tissue printing technology and human cardiac progenitor cells. Biomaterials 33:1782–1790CrossRefGoogle Scholar
  81. 81.
    Kang LH, Armstrong PA, Lee LJ, Duan B, Kang KH, Butcher JT (2017) Optimizing photo-encapsulation viability of heart valve cell types in 3D printable composite hydrogels. Ann Biomed Eng 45:360–377CrossRefGoogle Scholar
  82. 82.
    Zopf DA, Hollister SJ, Nelson ME, Ohye RG, Green GE (2013) Bioresorbable airway splint created with a three-dimensional printer. N Engl J Med 368:2043CrossRefGoogle Scholar
  83. 83.
    Rutz AL, Hyland KE, Jakus AE, Burghardt WR, Shah RN (2015) A multimaterial bioink method for 3D printing tunable, cell-compatible hydrogels. Adv Mater 27:1607–1614CrossRefGoogle Scholar
  84. 84.
    Li S, Yan Y, Xiong Z, Weng C, Zhang R, Wang X (2009) Gradient hydrogel construct based on an improved cell assembling system. J Bioact Compat Polym 24:84–99CrossRefGoogle Scholar
  85. 85.
    Li S, Xiong Z, Wang X, Yan Y, Liu H, Zhang R (2009) Direct fabrication of a hybrid cell/hydrogel construct by a double-nozzle assembling technology. J Bioact Compat Polym 24:249–265CrossRefGoogle Scholar
  86. 86.
    Zhao X, Wang X (2013) Preparation of an adipose-derived stem cell (ADSC)/fibrin-PLGA construct based on a rapid prototyping technique. J Bioact Compat Polym 28:191–203CrossRefGoogle Scholar
  87. 87.
    Zhao X, Liu L, Wang J, Xu YF, Zhang WM, Khang G, Wang X (2014) In vitro vascularization of a combined system based on a 3D bioprinting technique. J Tissue Eng Regen Med 10:833–842CrossRefGoogle Scholar
  88. 88.
    He K, Wang X (2011) Rapid prototyping of tubular polyurethane and cell/hydrogel construct. J Bioact Compat Polym 26:363–374CrossRefGoogle Scholar
  89. 89.
    Zhou X, Wang X (2015) Breast Engineering. In: Wang X (ed) Organ manufacturing. Nova Science Publishers Inc, Hauppauge, pp 357–384Google Scholar
  90. 90.
    Wang X (2013) Overview on biocompatibilities of implantable biomaterials. In: Lazinica R (ed) Advances in biomaterials science and biomedical applications in biomedicine. In Tech, Rijeka, pp 111–155Google Scholar
  91. 91.
    Wang X (2014) Spatial effects of stem cell engagement in 3D printing constructs. J Stem Cells Res Rev Rep 1:5–9Google Scholar
  92. 92.
    Wang X, Yan Y, Zhang R (2010) Gelatin-based hydrogels for controlled cell assembly. In: Ottenbrite RM (ed) Biomedical applications of hydrogels handbook. Springer, New York, pp 269–284CrossRefGoogle Scholar
  93. 93.
    Huang H, Sharma HS (2013) Neurorestoratology: one of the most promising new disciplines at the forefront of neuroscience and medicine. J Neuro-Oncol 1:37–41Google Scholar
  94. 94.
    Huang H, Raisman G, Sanberg PR, Sham HS (2015) Neurorestoratology. Nova Science Publishers, New YorkGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Center of Organ Manufacturing, Department of Tissue EngineeringChina Medical University (CMU)ShenyangPeople’s Republic of China
  2. 2.Center of Organ Manufacturing, Department of Mechanical EngineeringTsinghua UniversityBeijingPeople’s Republic of China
  3. 3.Tianjin Mifang Technology Company LimitedTianjinPeople’s Republic of China

Personalised recommendations