Skip to main content

Advertisement

SpringerLink
Log in

Whole-Organ Tissue Engineering: No Longer Just a Dream

  • Tissue Engineering and Regenerative Medicine: Organogenesis (Bryan Brown and Christopher L. Dearth,Section Editors)
  • Published:
Current Pathobiology Reports

Abstract

Purpose of Review

The true potential of the field of transplant surgery remains limited due to shortages of available transplantable allografts and, following transplantation, acute and chronic rejection with need for lifelong immune suppression. An alternative approach is to bioengineer organs to be utilized in vivo, replacing diseased or malfunctioning human organs. This revolutionary step in medicine could have virtually unlimited therapeutic potential.

Recent Findings

Multiple strategies have been used to replicate functional transplantable organs without deleterious host immune response. Common approaches include the use of decellularized tissue scaffolds and of 3D bioprinting. Continuing challenges include engraftment and maturation of recipient cells, and long-term tissue viability and function.

Summary

We will review in brief the history of the field and the progress to date with multiple organ systems, highlighting our personal experience in lung regeneration. Finally, we will discuss the challenges that lie ahead to reach the dream of fully functional and transplantable bioengineered organs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

TE:

Tissue Engineering

RM:

Regenerative medicine

TEM:

Transmission electron microscopy

3D:

Three Dimensional

ECM:

Extracellular matrix

HUVEC:

Human umbilical vein endothelial cells

FLC:

Fetal lung cells

MS1:

Murine endothelial cells

NKC:

Neonatal kidney cells

HBE:

Human Bronchial Epithelial cells

hMSC:

Human bone-marrow-derived mesenchymal stromal cells

HLF:

Human lung fibroblasts

CBF:

Human vascular endothelial cells

ESLD:

End-Stage Liver Disease

iPSC:

Induced pluripotent stem cells

References

Papers of particular interest, published recently, have been highlighted as • Of importance •• Of major importance

  1. Arulraj R, Neuberger J (2011) Liver transplantation: filling the gap between supply and demand. Clin Med (Lond) 11:194–198

    Article  Google Scholar 

  2. Barnieh L, Gill JS, Klarenbach S, Manns BJ (2013) The cost-effectiveness of using payment to increase living donor kidneys for transplantation. Clin J Am Soc Nephrol 8:2165–2173. doi:10.2215/CJN.03350313

    Article  PubMed  PubMed Central  Google Scholar 

  3. Macchiarini P, Jungebluth P, Go T et al (2008) Clinical transplantation of a tissue-engineered airway. Lancet 372:2023–2030. doi:10.1016/S0140-6736(08)61598-6

    Article  PubMed  Google Scholar 

  4. Macchiarini P, Walles T, Biancosino C, Mertsching H (2004) First human transplantation of a bioengineered airway tissue. J Thorac Cardiovasc Surg 128:638–641. doi:10.1016/j.jtcvs.2004.02.042

    Article  PubMed  Google Scholar 

  5. Atala A, Bauer SB, Soker S et al (2006) Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367:1241–1246. doi:10.1016/S0140-6736(06)68438-9

    Article  PubMed  Google Scholar 

  6. Tu DD, Chung YG, Gil ES et al (2013) Bladder tissue regeneration using acellular bi-layer silk scaffolds in a large animal model of augmentation cystoplasty. Biomaterials 34:8681–8689. doi:10.1016/j.biomaterials.2013.08.001

    Article  CAS  PubMed  Google Scholar 

  7. Jednak R (2014) The evolution of bladder augmentation: from creating a reservoir to reconstituting an organ. Front Pediatr 2:10. doi:10.3389/fped.2014.00010

    Article  PubMed  PubMed Central  Google Scholar 

  8. Orabi H, Bouhout S, Morissette A et al (2013) Tissue engineering of urinary bladder and urethra: advances from bench to patients. Sci World J 2013:154564. doi:10.1155/2013/154564

    Article  Google Scholar 

  9. Shin’oka T, Imai Y, Ikada Y (2001) Transplantation of a tissue-engineered pulmonary artery. N Engl J Med 344:532–533. doi:10.1056/NEJM200102153440717

    Article  PubMed  Google Scholar 

  10. L’Heureux N, McAllister TN, de la Fuente LM (2007) Tissue-engineered blood vessel for adult arterial revascularization. N Engl J Med 357:1451–1453. doi:10.1056/NEJMc071536

    Article  PubMed  Google Scholar 

  11. McAllister T, Maruszewski M, Garrido S et al (2009) Effectiveness of haemodialysis access with an autologous tissue-engineered vascular graft: a multicentre cohort study. The Lancet 373:1440–1446. doi:10.1016/S0140-6736(09)60248-8

    Article  Google Scholar 

  12. Badylak S, Taylor D, Uygun K (2011) Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. Annu Rev Biomed Eng 13:27–53. doi:10.1146/annurev-bioeng-071910-124743

    Article  CAS  PubMed  Google Scholar 

  13. Basu J, Mihalko KL, Payne R et al (2012) Extension of bladder-based organ regeneration platform for tissue engineering of esophagus. Med Hypotheses 78:231–234. doi:10.1016/j.mehy.2011.10.032

    Article  PubMed  Google Scholar 

  14. Peloso A, Katari R, Zambon J, Orlando G (2013) Sisyphus, the Giffen’s paradox and the Holy Grail: time for organ transplantation to transition toward a regenerative medicine-focused type of research. Expert Rev Clin Immunol 9:883–885. doi:10.1586/1744666X.2013.828887

    Article  CAS  PubMed  Google Scholar 

  15. Uygun B, Soto-Gutierrez A, Yagi H et al (2010) Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med 16:814–820. doi:10.1038/nm.2170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nelson CM, Bissell MJ (2006) Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Ann Rev Cell Dev Biol 22:287. doi:10.1146/annurev.cellbio.22.010305.104315

    Article  CAS  Google Scholar 

  17. Galili U (2015) Avoiding detrimental human immune response against Mammalian extracellular matrix implants. Tissue Eng Part B 21:231–241. doi:10.1089/ten.TEB.2014.0392

    Article  CAS  Google Scholar 

  18. Bader A, Schilling T, Teebken OE (1998) Tissue engineering of heart valves–human endothelial cell seeding of detergent acellularized porcine valves. Euro J Cardio-Thorac Surg 14(3):279–284. doi:10.1016/S1010-7940(98)00171-7

    Article  CAS  Google Scholar 

  19. Yannas IV (2013) Emerging rules for inducing organ regeneration. Biomaterials 34:321–330. doi:10.1016/j.biomaterials.2012.10.006

    Article  CAS  PubMed  Google Scholar 

  20. Lin Y-Q, Wang L-R, Pan L-L et al (2016) Kidney bioengineering in regenerative medicine: an emerging therapy for kidney disease. Cytotherapy 18:186–197. doi:10.1016/j.jcyt.2015.10.004

    Article  CAS  PubMed  Google Scholar 

  21. Crapo PM, Gilbert TW, Badylak SF (2011) An overview of tissue and whole organ decellularization processes. Biomaterials 32:3233–3243. doi:10.1016/j.biomaterials.2011.01.057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Brown BN, Freund JM, Han L et al (2011) Comparison of three methods for the derivation of a biologic scaffold composed of adipose tissue extracellular matrix. Tissue Eng Part C 17:411–421. doi:10.1089/ten.tec.2010.0342

    Article  CAS  Google Scholar 

  23. Badylak SF, Valentin JE, Ravindra AK et al (2008) Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A 14:1835–1842. doi:10.1089/ten.tea.2007.026

    Article  CAS  PubMed  Google Scholar 

  24. Liu Y, Yang R, He Z, Gao W-Q (2013) Generation of functional organs from stem cells. Cell Regeneration 2:1. doi:10.1186/2045-9769-2-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Guyette JP, Charest JM, Mills RW et al (2016) Bioengineering human myocardium on native extracellular matrix. Circ Res 118:56–72. doi:10.1161/CIRCRESAHA.115.306874

    Article  CAS  PubMed  Google Scholar 

  26. Ott HC, Matthiesen TS, Goh S-KK et al (2008) Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med 14:213–221. doi:10.1038/nm1684

    Article  CAS  PubMed  Google Scholar 

  27. Wainwright JM, Czajka CA, Patel UB et al (2010) Preparation of cardiac extracellular matrix from an intact porcine heart. Tissue Eng Part 16:525–532. doi:10.1089/ten.TEC.2009.0392

    Article  CAS  Google Scholar 

  28. Collin de l’Hortet A, Takeishi K, Guzman-Lepe J et al (2015) Liver regenerative-transplantation: regrow and reboot. Am J Transplant. doi:10.1111/ajt.13678

    Google Scholar 

  29. Orman E, Mayorga M, Wheeler S et al (2015) Declining liver graft quality threatens the future of liver transplantation in the United States. Liver Transplant 21:1040–1050. doi:10.1002/lt.24160

    Article  Google Scholar 

  30. Zhang H, Zhang Y, Ma F et al (2015) Orthotopic transplantation of decellularized liver scaffold in mice. Int J Clin Exp Med 8:598–606

    PubMed  PubMed Central  Google Scholar 

  31. Palakkan AA, Hay DC, Anil Kumar PR et al (2013) Liver tissue engineering and cell sources: issues and challenges. Liver Int 33:666–676. doi:10.1111/liv.12134

    Article  CAS  PubMed  Google Scholar 

  32. De Kock J, Ceelen L, De Spiegelaere W et al (2011) Simple and quick method for whole-liver decellularization: a novel in vitro three-dimensional bioengineering tool? Arch Toxicol 85:607–612. doi:10.1007/s00204-011-0706-1

    Article  Google Scholar 

  33. •• Ko I, Peng L, Peloso A, et al. (2015) Bioengineered transplantable porcine livers with re-endothelialized vasculature. Biomaterials 40:72–79. doi: 10.1016/j.biomaterials.2014.11.027. This article performs de and re-cellularization of porcine liver, and performs both in and ex vivo experiments to show clinical feasibility of a clinically relevant sized-match engineered liver

  34. Rogers J, Katari R, Gifford S et al (2015) Kidney transplantation, bioengineering and regeneration: an originally immunology-based discipline destined to transition towards ad hoc organ manufacturing and repair. Expert Rev Clin Immunol. doi:10.1586/1744666X.2016.1112268

    PubMed  Google Scholar 

  35. Petrosyan A, Zanusso I, Lavarreda-Pearce M et al (2016) Decellularized renal matrix and regenerative medicine of the kidney: a different point of view. Tissue Eng Part B . doi:10.1089/ten.TEB.2015.0368

    Google Scholar 

  36. •• Song JJ, Guyette JP, Gilpin SE, et al. (2013) Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nature medicine 19:646–651. doi:10.1038/nm.3154. This study demonstrates the feasibility of utilizing the decellularization-recellularization approach for kidney bioengineering, including the in vivo efficacy of implanted rat kidneys able to produce urine

  37. Orlando G, Bendala JD, Shupe T et al (2013) Cell and organ bioengineering technology as applied to gastrointestinal diseases. Gut 62:774–786. doi:10.1136/gutjnl-2011-301111

    Article  CAS  PubMed  Google Scholar 

  38. Merani S, Shapiro AM (2006) Current status of pancreatic islet transplantation. Clin Sci 110:611–625. doi:10.1042/CS20050342

    Article  CAS  PubMed  Google Scholar 

  39. Bellin MD, Kandaswamy R, Parkey J et al (2008) Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes. Am J Transplant 8:2463–2470. doi:10.1111/j.1600-6143.2008.02404.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Orlando G, Wood KJ, Coppi P et al (2012) Regenerative medicine as applied to general surgery. Ann Surg 255:867. doi:10.1097/SLA.0b013e318243a4db

    Article  PubMed  PubMed Central  Google Scholar 

  41. De Carlo E, Baiguera S, Conconi MT et al (2010) Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: in vitro and in vivo studies. Int J Mol Med 25:195–202

    PubMed  Google Scholar 

  42. Weiss DJ, Elliott M, Jang Q et al (2014) Tracheal bioengineering: the next steps. Proceeds of an international society of cell therapy pulmonary cellular therapy signature series workshop, Paris, France, April 22, 2014. Cytotherapy 16:1601–1613. doi:10.1016/j.jcyt.2014.10.012

    Article  PubMed  Google Scholar 

  43. Martinod E, Seguin A, Radu DM, Boddaert G (2013) Airway transplantation: a challenge for regenerative medicine. Eur J Med Res 18(1):1

    Article  Google Scholar 

  44. Martinod E, Radu DM, Chouahnia K et al (2011) Human transplantation of a biologic airway substitute in conservative lung cancer surgery. Ann Thorac Surg 91:837–842. doi:10.1016/j.athoracsur.2010.11.013

    Article  PubMed  Google Scholar 

  45. Martinod E, Zegdi R, Zakine G et al (2001) A novel approach to tracheal replacement: the use of an aortic graft. J Thorac Cardiovasc Surg 122:197–198. doi:10.1067/mtc.2001.114346

    Article  CAS  PubMed  Google Scholar 

  46. • Zopf DA, Hollister SJ, Nelson ME, et al. (2013) Bioresorbable airway splint created with a three-dimensional printer. N Engl J Med 368:2043–5. doi:10.1056/NEJMc1206319. This article showcases the clinical use of a tissue engineered airway splint created using a 3D printer for a newborn with severe tracheobronchomalacia

  47. Chen MK, Badylak SF (2001) Small bowel tissue engineering using small intestinal submucosa as a scaffold. J Surg Res 99:352–358. doi:10.1006/jsre.2001.6199

    Article  CAS  PubMed  Google Scholar 

  48. Grikscheit TC, Siddique A, Ochoa ER et al (2004) Tissue-engineered small intestine improves recovery after massive small bowel resection. Ann Surg 240:748–754. doi:10.1097/01.sla.0000143246.07277.73

    Article  PubMed  PubMed Central  Google Scholar 

  49. Sala FGG, Kunisaki SM, Ochoa ER et al (2009) Tissue-engineered small intestine and stomach form from autologous tissue in a preclinical large animal model. J Surg Res 156:205–212. doi:10.1016/j.jss.2009.03.062

    Article  PubMed  Google Scholar 

  50. Grikscheit TC, Ochoa ER, Ramsanahie A et al (2003) Tissue-engineered large intestine resembles native colon with appropriate in vitro physiology and architecture. Ann Surg 238:35–41. doi:10.1097/01.SLA.0000074964.77367.4a

    PubMed  PubMed Central  Google Scholar 

  51. Somara S, Gilmont RR, Dennis RG, Bitar KN (2009) Bioengineered internal anal sphincter derived from isolated human internal anal sphincter smooth muscle cells. Gastroenterology 137:53–61. doi:10.1053/j.gastro.2009.03.036

    Article  CAS  PubMed  Google Scholar 

  52. Nakase Y, Nakamura T, Kin S, Nakashima S (2008) Intrathoracic esophageal replacement by in situ tissue-engineered esophagus. J thorac cardiovasc surg 136:850–859. doi:10.1016/j.jtcvs.2008.05.027

    Article  PubMed  Google Scholar 

  53. Hori Y, Nakamura T, Kimura D et al (2002) Functional analysis of the tissue-engineered stomach wall. Artif Organs 26:868–872

    Article  PubMed  Google Scholar 

  54. Maemura T, Shin M, Kinoshita M et al (2008) A tissue-engineered stomach shows presence of proton pump and G-cells in a rat model, resulting in improved anemia following total gastrectomy. Artif Organs 32:234–239. doi:10.1111/j.1525-1594.2007.00528.x

    Article  PubMed  Google Scholar 

  55. Speer AL, Sala FG, Matthews JA, Grikscheit TC (2011) Murine tissue-engineered stomach demonstrates epithelial differentiation. J Surg Res 171:6–14. doi:10.1016/j.jss.2011.03.062

    Article  CAS  PubMed  Google Scholar 

  56. Heimbach D, Luterman A, Burke J, Cram A (1988) Artificial dermis for major burns. A multi-center randomized clinical trial. Ann Surg 208(3):313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. MacNeil S (2007) Progress and opportunities for tissue-engineered skin. Nature 445(7130):874–880

    Article  CAS  PubMed  Google Scholar 

  58. Algzlan H, Varada S (2015) Three-dimensional printing of the skin. JAMA Dermatol 151:207. doi:10.1001/jamadermatol.2014.1198

    Article  PubMed  Google Scholar 

  59. Scuderi N, Onesti MG, Bistoni G et al (2008) The clinical application of autologous bioengineered skin based on a hyaluronic acid scaffold. Biomaterials 29:1620–1629. doi:10.1016/j.biomaterials.2007.12.024

    Article  CAS  PubMed  Google Scholar 

  60. Ma X, He Z, Han F et al (2016) Preparation of collagen/hydroxyapatite/alendronate hybrid hydrogels as potential scaffolds for bone regeneration. Colloids Surf B Biointerfaces 143:81–87. doi:10.1016/j.colsurfb.2016.03.025

    Article  CAS  PubMed  Google Scholar 

  61. Ducheyne P, Qiu Q (1999) Bioactive ceramics: the effect of surface reactivity on bone formation and bone cell function. Biomaterials 20(23):2287–2303

    Article  CAS  PubMed  Google Scholar 

  62. Peng H, Liu X, Wang R et al (2014) Emerging nanostructured materials for musculoskeletal tissue engineering. J Mater Chem B 2:6435–6461. doi:10.1039/C4TB00344F

    Article  CAS  Google Scholar 

  63. Deepthi S, Venkatesan J, Kim S-KK et al (2016) An overview of chitin or chitosan/nano ceramic composite scaffolds for bone tissue engineering. Int J Biol Macromol. doi:10.1016/j.ijbiomac.2016.03.041

    Google Scholar 

  64. Venkatesan J, Kim S-K (2010) Chitosan composites for bone tissue engineering—an overview. Mar drugs 8:2252–2266. doi:10.3390/md8082252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Warnke PH, Springer IN, Wiltfang J et al (2004) Growth and transplantation of a custom vascularised bone graft in a man. Lancet 364:766–770. doi:10.1016/S0140-6736(04)16935-3

    Article  CAS  PubMed  Google Scholar 

  66. Quarto R, Mastrogiacomo M, Cancedda R et al (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344:385–386. doi:10.1056/NEJM200102013440516

    Article  CAS  PubMed  Google Scholar 

  67. Borschel G, Dennis R, Kuzon W (2004) Contractile skeletal muscle tissue-engineered on an acellular scaffold. Plast Reconstr Surg 113:595. doi:10.1097/01.PRS.0000101064.62289.2F

    Article  PubMed  Google Scholar 

  68. Kroehne V, Heschel I, Schügner F et al (2008) Use of a novel collagen matrix with oriented pore structure for muscle cell differentiation in cell culture and in grafts. J Cell Mol Med 12:1640–1648. doi:10.1111/j.1582-4934.2008.00238.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Qazi T, Mooney D, Pumberger M et al (2015) Biomaterials based strategies for skeletal muscle tissue engineering: existing technologies and future trends. Biomaterials 53:502–521. doi:10.1016/j.biomaterials.2015.02.110

    Article  CAS  PubMed  Google Scholar 

  70. Liao IC, Liu JB, Bursac N, Leong KW (2008) Effect of electromechanical stimulation on the maturation of myotubes on aligned electrospun fibers. Cell Mol Bioeng 1(2–3):133–145. doi:10.1007/s12195-008-0021-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Langelaan M, Boonen K (2011) Advanced maturation by electrical stimulation: differences in response between C2C12 and primary muscle progenitor cells. J Tissue Eng Regen Med 5(7):529–539. doi:10.1002/term.345

    Article  PubMed  Google Scholar 

  72. Guillemette MD, Gauvin R, Perron C (2010) Tissue-engineered vascular adventitia with vasa vasorum improves graft integration and vascularization through inosculation. Tissue Eng Part A 16(8):2617–2626. doi:10.1089/ten.tea.2009.0612

    Article  CAS  PubMed  Google Scholar 

  73. Wagner DE, Bonenfant NR, Sokocevic D et al (2014) Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration. Biomaterials 35:2664–2679. doi:10.1016/j.biomaterials.2013.11.078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Zvarova B, Uhl FE, Uriarte JJ et al (2016) Residual detergent detection method for non-destructive cytocompatibility evaluation of decellularized whole lung scaffolds. Tissue Eng Part C. doi:10.1089/ten.TEC.2015.0439

    Google Scholar 

  75. Crabbé A, Liu Y, Sarker SF et al (2015) Recellularization of decellularized lung scaffolds is enhanced by dynamic suspension culture. PLoS ONE 10:e0126846. doi:10.1371/journal.pone.0126846

    Article  PubMed  PubMed Central  Google Scholar 

  76. Booth AJ, Hadley R, Cornett AM, Dreffs AA (2012) Acellular normal and fibrotic human lung matrices as a culture system for in vitro investigation. Am J Resp Criti Care Med 186(9):866–876. doi:10.1164/rccm.201204-0754OC

    Article  CAS  Google Scholar 

  77. Godin LM, Sandri BJ, Wagner DE et al (2016) Decreased laminin expression by human lung epithelial cells and fibroblasts cultured in acellular lung scaffolds from aged mice. PLoS ONE 11:e0150966. doi:10.1371/journal.pone.0150966

    Article  PubMed  PubMed Central  Google Scholar 

  78. Cruz FF, Borg ZD, Goodwin M et al (2015) Freshly thawed and continuously cultured human bone marrow-derived mesenchymal stromal cells comparably ameliorate allergic airways inflammation in immunocompetent mice. Stem Cells Transl Med 4:615–624. doi:10.5966/sctm.2014-0268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Wagner DE, Fenn SL, Bonenfant NR et al (2014) Design and synthesis of an artificial pulmonary pleura for high throughput studies in acellular human lungs. Cell Mol Bioeng 7:184–195. doi:10.1007/s12195-014-0323-1

    Article  PubMed  PubMed Central  Google Scholar 

  80. Sokocevic D, Bonenfant NR, Wagner DE et al (2013) The effect of age and emphysematous and fibrotic injury on the re-cellularization of de-cellularized lungs. Biomaterials 34:3256–3269. doi:10.1016/j.biomaterials.2013.01.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. La Francesca S, Ting AE, Sakamoto J et al (2014) Multipotent adult progenitor cells decrease cold ischemic injury in ex vivo perfused human lungs: an initial pilot and feasibility study. Trans Res 3:19. doi:10.1186/2047-1440-3-19

    Google Scholar 

  82. Collin de l’Hortet A, Takeishi K, Guzman-Lepe J et al (2015) Liver regenerative-transplantation: regrow and reboot. Am J Transplant. doi:10.1111/ajt.13678

    Google Scholar 

  83. Yoo S-S (2015) 3D-printed biological organs: medical potential and patenting opportunity. Expert Opin Ther Pat 25:507–511. doi:10.1517/13543776.2015.1019466

    Article  CAS  PubMed  Google Scholar 

  84. Murphy SV, Skardal A, Atala A (2013) Evaluation of hydrogels for bio-printing applications. J Biomed Mater Res A 101:272–284. doi:10.1002/jbm.a.3432

    Article  PubMed  Google Scholar 

  85. Markstedt K, Mantas A, Tournier I et al (2015) 3D Bioprinting human chondrocytes with nanocellulose-alginate bioink for cartilage tissue engineering applications. Biomacromolecules 16:1489–1496. doi:10.1021/acs.biomac.5b00188

    Article  CAS  PubMed  Google Scholar 

  86. Pati F, Jang J, Ha D-H et al (2014) Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun 5:3935. doi:10.1038/ncomms4935

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhao Y, Li Y, Mao S et al (2015) The influence of printing parameters on cell survival rate and printability in microextrusion-based 3D cell printing technology. Biofabrication 7:045002. doi:10.1088/1758-5090/7/4/045002

    Article  PubMed  Google Scholar 

  88. Wiles KL, Fishman JM, De Coppi P, Birchall M (2015) The host immune response to tissue-engineered organs: current problems and future directions. Tissue Eng Part B. doi:10.1089/ten.TEB.2015.0376

    Google Scholar 

  89. Soto-Gutierrez A, Wertheim J, Ott H, Gilbert T (2012) Perspectives on whole-organ assembly: moving toward transplantation on demand. J Clin Investig 122:3817–3823. doi:10.1172/JCI61974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Daly K, Stewart-Akers A, Hara H et al (2009) Effect of the αgal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model. Tissue Eng Part A 15:3877–3888. doi:10.1089/ten.tea.2009.0089

    Article  CAS  PubMed  Google Scholar 

  91. Galili U, Shohet SB, Kobrin E, Stults CL (1988) Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. J Biol 263(33):17755–17762

    CAS  Google Scholar 

  92. Spiller K, Freytes D, Vunjak-Novakovic G (2014) Macrophages modulate engineered human tissues for enhanced vascularization and healing. Ann Biomed Eng. doi:10.1007/s10439-014-1156-8

    PubMed  PubMed Central  Google Scholar 

  93. Badylak SF, Valentin JE, Ravindra AK et al (2008) Macrophage phenotype as a determinant of biologic scaffold remodeling. Tissue Eng Part A 14:1835–1842. doi:10.1089/ten.tea.2007.0264

    Article  CAS  PubMed  Google Scholar 

  94. Dylak S (2002) In vivo studies to evaluate tissue engineering techniques. Ann N Y Acad Sci 961:302–304. doi:10.1111/j.1749-6632.2002.tb03107.x

    Article  Google Scholar 

  95. Jeyaraj R, Natasha G, Kirby G et al (2015) Vascularisation in regenerative therapeutics and surgery. Mater Sci Eng 54:225–238. doi:10.1016/j.msec.2015.05.045

    Article  CAS  Google Scholar 

  96. Phelps E, García A (2010) Engineering more than a cell: vascularization strategies in tissue engineering. Curr Opin Biotechnol 21:704–709. doi:10.1016/j.copbio.2010.06.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Murphy SV, Skardal A, Atala A (2013) Evaluation of hydrogels for bio-printing applications. J Biomed Mater Res A 101:272–284. doi:10.1002/jbm.a.34326

    Article  PubMed  Google Scholar 

  98. • Hooper R, Hernandez K, Boyko T, et al. (2014) Fabrication and In Vivo Microanastomosis of Vascularized Tissue-Engineered Constructs. Tissue Eng Pt A 20:2711–2719. doi:10.1089/ten.TEA.2013.0583. This article demonstrates the feasibility of vascularizing bioengineered hydrogels in an in vivo model utilizing endothelialized micro-channels, thus overcoming a major hurdle for use of this material in whole organ engineering

  99. Bishop A, Sharland A, Ierino F et al (2011) Operational tolerance in organ transplantation versus tissue engineering: into the future. Transplantation 92:e39. doi:10.1097/TP.0b013e31822f59ff

    Article  Google Scholar 

  100. Orlando G, Wood KJ, Soker S, Stratta RJ (2011) How regenerative medicine may contribute to the achievement of an immunosuppression-free state. Transplantation 92:e36–8; author reply e39. doi:10.1097/TP.0b013e31822f59d8

  101. Petersen TH, Calle EA, Zhao L et al (2010) Tissue-engineered lungs for in vivo Implantation. Science 329:538–541. doi:10.1126/science.1189345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Ott HC, Clippinger B, Conrad C et al (2010) Regeneration and orthotopic transplantation of a bioartificial lung. Nat Med 16:927–933. doi:10.1038/nm.2193

    Article  CAS  PubMed  Google Scholar 

  103. Chouillard E, Chahine E, Allaire E et al (2016) Small bowel in vivo bioengineering using an aortic matrix in a porcine model. Surg Endosc. doi:10.1007/s00464-016-4815-z

    PubMed  Google Scholar 

  104. Shin’oka T, Imai Y, Ikada Y (2001) Transplantation of a tissue-engineered pulmonary artery. N Engl J Med 344:532–533. doi:10.1056/NEJM200102153440717

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Bryan Brown for his insight and collaboration with the Weiss lab. Further, we thank Franzi Uhl, Amy Coffey, Jacob Dearborn, and all members of the Weiss Lab who contributed to our prior research. We would like to acknowledge the giants who came before us in the field, and those who continue to push the field forward to this day. Finally, we would like to acknowledge our families, particularly Lia Nelson Wrenn, for their support. No writing assistance was utilized in the creation of this manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Vermont Medical Center, 111 Colchester Avenue, Burlington, VT, 05401, USA

    Sean M. Wrenn

  2. Department of Medicine, Vermont Lung Center, Health Science Research Facility, University of Vermont College of Medicine, Rm 226 149 Beaumont Avenue, Burlington, VT, 05405, USA

    Daniel J. Weiss

Authors
  1. Sean M. Wrenn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel J. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sean M. Wrenn.

Ethics declarations

Conflict of interest

Sean M. Wrenn declares that he has no conflict of interest. Daniel Weiss receives research funding from Athersys Inc. and from United Therapeutics Inc. In addition, Dr. Weiss has a patent Provisional Patent Application No. 61/810,966 pending, a patent Provisional Patent Application No. 62/147,943 pending, and a patent null pending.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical collection on Tissue Engineering and Regenerative Medicine: Organogenesis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wrenn, S.M., Weiss, D.J. Whole-Organ Tissue Engineering: No Longer Just a Dream. Curr Pathobiol Rep 4, 87–98 (2016). https://doi.org/10.1007/s40139-016-0110-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40139-016-0110-x

Keywords

Search

Navigation