Naturally-Derived Biomaterials for Tissue Engineering Applications

  • Matthew Brovold
  • Joana I. Almeida
  • Iris Pla-Palacín
  • Pilar Sainz-Arnal
  • Natalia Sánchez-Romero
  • Jesus J. Rivas
  • Helen Almeida
  • Pablo Royo Dachary
  • Trinidad Serrano-Aulló
  • Shay SokerEmail author
  • Pedro M. BaptistaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1077)


Naturally-derived biomaterials have been used for decades in multiple regenerative medicine applications. From the simplest cell microcarriers made of collagen or alginate, to highly complex decellularized whole-organ scaffolds, these biomaterials represent a class of substances that is usually first in choice at the time of electing a functional and useful biomaterial. Hence, in this chapter we describe the several naturally-derived biomaterials used in tissue engineering applications and their classification, based on composition. We will also describe some of the present uses of the generated tissues like drug discovery, developmental biology, bioprinting and transplantation.


Naturally-derived materials Tissue decellularization Tissue engineering Protein-based biomaterials Polysaccharide-based biomaterials Glycosaminoglycans Extracellular matrix-derived biomaterials Solid organ bioengineering Regulatory landscape for naturally-derived biomaterials 



This work was supported by Gobierno de Aragón and Fondo Social Europeo through a predoctoral Fellowship DGA C066/2014 (P. S-A), Instituto de Salud Carlos III, through a predoctoral fellowship i-PFIS IFI15/00158 (I. P-P). N. S-R was supported by a POCTEFA/Refbio II research grant and FGJ Gobierno de Aragón. J.I.A was supported by Fundação para a Ciência e a Tecnologia (Portugal), through a predoctoral Fellowship SFRH/BD/116780/2016. PMB was supported with the project PI15/00563 from Instituto de Salud Carlos III, Spain.


  1. 1.
    Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926CrossRefGoogle Scholar
  2. 2.
    Hendow EK, Guhmann P, Wright B, Sofokleous P, Parmar N, Day RM (2016) Biomaterials for hollow organ tissue engineering. Fibrogenesis Tissue Repair 9:3PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Ikada Y (2006) Challenges in tissue engineering. J R Soc Interface 3:589–601PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Mazza G, Rombouts K, Rennie Hall A, Urbani L, Vinh Luong T, Al-Akkad W, Longato L et al (2015) Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation. Sci Rep 5:13079PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Azuma K, Izumi R, Osaki T, Ifuku S, Morimoto M, Saimoto H, Minami S et al (2015) Chitin, chitosan, and its derivatives for wound healing: old and new materials. J Funct Biomater 6:104–142PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Bao Ha TL, Minh T, Nguyen D, Minh D (2013) Naturally derived biomaterials: preparation and application. In: Regenerative medicine and tissue engineering. Scholar
  7. 7.
    Gunatillake PA, Adhikari R (2003) Biodegradable synthetic polymers for tissue engineering. Eur Cell Mater 5:1–16 discussion 16PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Willerth SM, Sakiyama-Elbert SE (2008) Combining stem cells and biomaterial scaffolds for constructing tissues and cell delivery. In: Stem book. Harvard Stem Cell Institute, Cambridge, MAGoogle Scholar
  9. 9.
    Bhat S, Kumar A (2013) Biomaterials and bioengineering tomorrow’s healthcare. Biomatter 3:e24717PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Yannas IV, Lee E, Orgill DP, Skrabut EM, Murphy GF (1989) Synthesis and characterization of a model extracellular matrix that induces partial regeneration of adult mammalian skin. Proc Natl Acad Sci U S A 86:933–937PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB (2006) Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367:1241–1246PubMedCrossRefGoogle Scholar
  12. 12.
    Warnke PH, Springer IN, Wiltfang J, Acil Y, Eufinger H, Wehmoller M, Russo PA et al (2004) Growth and transplantation of a custom vascularised bone graft in a man. Lancet 364:766–770PubMedCrossRefGoogle Scholar
  13. 13.
    Zacchi V, Soranzo C, Cortivo R, Radice M, Brun P, Abatangelo G (1998) In vitro engineering of human skin-like tissue. J Biomed Mater Res 40:187–194PubMedCrossRefGoogle Scholar
  14. 14.
    Kaushal S, Amiel GE, Guleserian KJ, Shapira OM, Perry T, Sutherland FW, Rabkin E et al (2001) Functional small-diameter neovessels created using endothelial progenitor cells expanded ex vivo. Nat Med 7:1035–1040PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Griffith LG, Naughton G (2002) Tissue engineering – current challenges and expanding opportunities. Science 295:1009–1014CrossRefPubMedGoogle Scholar
  16. 16.
    Sivaraman A, Leach JK, Townsend S, Iida T, Hogan BJ, Stolz DB, Fry R et al (2005) A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction. Curr Drug Metab 6:569–591PubMedCrossRefGoogle Scholar
  17. 17.
    Moran EC, Dhal A, Vyas D, Lanas A, Soker S, Baptista PM (2014) Whole-organ bioengineering: current tales of modern alchemy. Transl Res 163:259–267PubMedCrossRefGoogle Scholar
  18. 18.
    Peloso A, Dhal A, Zambon JP, Li P, Orlando G, Atala A, Soker S (2015) Current achievements and future perspectives in whole-organ bioengineering. Stem Cell Res Ther 6:107PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S (2011) The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology 53:604–617CrossRefGoogle Scholar
  20. 20.
    Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA (2008) Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med 14:213–221PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Katari R, Peloso A, Zambon JP, Soker S, Stratta RJ, Atala A, Orlando G (2014) Renal bioengineering with scaffolds generated from human kidneys. Nephron Exp Nephrol 126:119PubMedCrossRefGoogle Scholar
  22. 22.
    Wagner DE, Bonvillain RW, Jensen T, Girard ED, Bunnell BA, Finck CM, Hoffman AM et al (2013) Can stem cells be used to generate new lungs? Ex vivo lung bioengineering with decellularized whole lung scaffolds. Respirology 18:895–911PubMedCrossRefGoogle Scholar
  23. 23.
    Baptista PM, Orlando G, Mirmalek-Sani SH, Siddiqui M, Atala A, Soker S (2009) Whole organ decellularization – a tool for bioscaffold fabrication and organ bioengineering. Conf Proc IEEE Eng Med Biol Soc 2009:6526–6529PubMedGoogle Scholar
  24. 24.
    Bayrak A, Tyralla M, Ladhoff J, Schleicher M, Stock UA, Volk HD, Seifert M (2010) Human immune responses to porcine xenogeneic matrices and their extracellular matrix constituents in vitro. Biomaterials 31:3793–3803PubMedCrossRefGoogle Scholar
  25. 25.
    Bastian F, Stelzmuller ME, Kratochwill K, Kasimir MT, Simon P, Weigel G (2008) IgG deposition and activation of the classical complement pathway involvement in the activation of human granulocytes by decellularized porcine heart valve tissue. Biomaterials 29:1824–1832PubMedCrossRefGoogle Scholar
  26. 26.
    A Brief History of Biomedical Materials (2009) [PDF] DSM, pp 1–2. Available at:
  27. 27.
    Heness G, Ben-Nissan B (2004) Innovative bioceramics. Mat For 27:104–114Google Scholar
  28. 28.
    Pachence JM (1996) Collagen-based devices for soft tissue repair. J Biomed Mater Res 33:35–40PubMedCrossRefGoogle Scholar
  29. 29.
    Sinha VR, Trehan A (2003) Biodegradable microspheres for protein delivery. J Control Release 90:261–280CrossRefPubMedGoogle Scholar
  30. 30.
    Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM (2008) Properties of the amniotic membrane for potential use in tissue engineering. Eur Cell Mater 15:88–99PubMedCrossRefGoogle Scholar
  31. 31.
    Loss M, Wedler V, Kunzi W, Meuli-Simmen C, Meyer VE (2000) Artificial skin, split-thickness autograft and cultured autologous keratinocytes combined to treat a severe burn injury of 93% of TBSA. Burns 26:644–652CrossRefGoogle Scholar
  32. 32.
    Branski LK, Herndon DN, Celis MM, Norbury WB, Masters OE, Jeschke MG (2008) Amnion in the treatment of pediatric partial-thickness facial burns. Burns 34:393–399PubMedCrossRefGoogle Scholar
  33. 33.
    Lee CH, Singla A, Lee Y (2001) Biomedical applications of collagen. Int J Pharm 221:1–22CrossRefPubMedGoogle Scholar
  34. 34.
    Robb K, Shridhar A, Flynn L (2017) Decellularized matrices as cell-instructive scaffolds to guide tissue-specific regeneration. ACS Biomater Sci Eng. Article.
  35. 35.
    Stock P, Winkelmann C, Thonig A, Böttcher G, Wenske G, Christ B (2012) Application of collagen coated silicone scaffolds for the three-dimensional cell culture of primary rat hepatocytes. FASEB J 26:274.272–274.272Google Scholar
  36. 36.
    Wang Y, Gunasekara DB, Reed MI, DiSalvo M, Bultman SJ, Sims CE, Magness ST et al (2017) A microengineered collagen scaffold for generating a polarized crypt-villus architecture of human small intestinal epithelium. Biomaterials 128:44–55PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Echave MC, Saenz del Burgo L, Pedraz JL, Orive G (2017) Gelatin as biomaterial for tissue engineering. Curr Pharm Des 23:3567–3584PubMedCrossRefGoogle Scholar
  38. 38.
    Tayebi L, Rasoulianboroujeni M, Moharamzadeh K, Almela TKD, Cui Z, Ye H (2018) 3D-printed membrane for guided tissue regeneration. Mater Sci Eng C Mater Biol Appl 84:148–158PubMedCrossRefGoogle Scholar
  39. 39.
    Elamparithi A, Punnoose AM, Paul SFD, Kuruvilla S (2017) Gelatin electrospun nanofibrous matrices for cardiac tissue engineering applications. Int J Polym Mater Polym Biomater 66:20–27CrossRefGoogle Scholar
  40. 40.
    Gu Y, Bai Y, Zhang D (2018) Osteogenic stimulation of human dental pulp stem cells with a novel gelatin-hydroxyapatite-tricalcium phosphate scaffold. J Biomed Mater Res A 106:1851–1861PubMedCrossRefGoogle Scholar
  41. 41.
    Gattazzo F, De Maria C, Rimessi A, Dona S, Braghetta P, Pinton P, Vozzi G et al (2018) Gelatin-genipin-based biomaterials for skeletal muscle tissue engineering. J Biomed Mater Res B Appl Biomater 00B:000–000Google Scholar
  42. 42.
    Lewis PL, Green RM, Shah RN (2018) 3D-printed gelatin scaffolds of differing pore geometry modulate hepatocyte function and gene expression. Acta Biomater 69:63–70PubMedCrossRefGoogle Scholar
  43. 43.
    Kilic Bektas C, Hasirci V (2017) Mimicking corneal stroma using keratocyte-loaded photopolymerizable methacrylated gelatin hydrogels. J Tissue Eng Regen Med 12:e1899–e1910CrossRefGoogle Scholar
  44. 44.
    Amer MH, Rose F, Shakesheff KM, White LJ (2018) A biomaterials approach to influence stem cell fate in injectable cell-based therapies. Stem Cell Res Ther 9:39PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Vepari C, Kaplan DL (2007) Silk as a biomaterial. Prog Polym Sci 32:991–1007PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Sawatjui N, Limpaiboon T, Schrobback K, Klein T (2018) Biomimetic scaffolds and dynamic compression enhance the properties of chondrocyte- and MSC-based tissue-engineered cartilage. J Tissue Eng Regen Med 12:1220–1229PubMedCrossRefGoogle Scholar
  47. 47.
    Kim DK, In Kim J, Sim BR, Khang G (2017) Bioengineered porous composite curcumin/silk scaffolds for cartilage regeneration. Mater Sci Eng C Mater Biol Appl 78:571–578PubMedCrossRefGoogle Scholar
  48. 48.
    Warnecke D, Schild NB, Klose S, Joos H, Brenner RE, Kessler O, Skaer N et al (2017) Friction properties of a new silk fibroin scaffold for meniscal replacement. Tribol Int 109:586–592PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Hu Y, Ran J, Zheng Z, Jin Z, Chen X, Yin Z, Tang C et al (2018) Exogenous stromal derived factor-1 releasing silk scaffold combined with intra-articular injection of progenitor cells promotes bone-ligament-bone regeneration. Acta Biomater 71:168–183PubMedCrossRefGoogle Scholar
  50. 50.
    Sack BS, Mauney JR, Estrada CR Jr (2016) Silk fibroin scaffolds for urologic tissue engineering. Curr Urol Rep 17:16PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Ye Q, Zund G, Benedikt P, Jockenhoevel S, Hoerstrup SP, Sakyama S, Hubbell JA et al (2000) Fibrin gel as a three dimensional matrix in cardiovascular tissue engineering. Eur J Cardiothorac Surg 17:587–591PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Seyedi F, Farsinejad A, Nematollahi-Mahani SN (2017) Fibrin scaffold enhances function of insulin producing cells differentiated from human umbilical cord matrix-derived stem cells. Tissue Cell 49:227–232PubMedCrossRefGoogle Scholar
  53. 53.
    Munirah S, Kim SH, Ruszymah BH, Khang G (2008) The use of fibrin and poly(lactic-co-glycolic acid) hybrid scaffold for articular cartilage tissue engineering: an in vivo analysis. Eur Cell Mater 15:41–52PubMedCrossRefGoogle Scholar
  54. 54.
    Khodakaram-Tafti A, Mehrabani D, Shaterzadeh-Yazdi H (2017) An overview on autologous fibrin glue in bone tissue engineering of maxillofacial surgery. Dent Res J (Isfahan) 14:79–86Google Scholar
  55. 55.
    Eo MY, Fan H, Cho YJ, Kim SM, Lee SK (2016) Cellulose membrane as a biomaterial: from hydrolysis to depolymerization with electron beam. Biomater Res 20:16PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Entcheva E, Bien H, Yin L, Chung CY, Farrell M, Kostov Y (2004) Functional cardiac cell constructs on cellulose-based scaffolding. Biomaterials 25:5753–5762PubMedCrossRefGoogle Scholar
  57. 57.
    Svensson A, Nicklasson E, Harrah T, Panilaitis B, Kaplan DL, Brittberg M, Gatenholm P (2005) Bacterial cellulose as a potential scaffold for tissue engineering of cartilage. Biomaterials 26:419–431PubMedCrossRefGoogle Scholar
  58. 58.
    Wang B, Lv X, Chen S, Li Z, Yao J, Peng X, Feng C et al (2018) Use of heparinized bacterial cellulose based scaffold for improving angiogenesis in tissue regeneration. Carbohydr Polym 181:948–956PubMedCrossRefGoogle Scholar
  59. 59.
    Park BK, Kim MM (2010) Applications of chitin and its derivatives in biological medicine. Int J Mol Sci 11:5152–5164PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Venkatesan J, Kim SK (2010) Chitosan composites for bone tissue engineering – an overview. Mar Drugs 8:2252–2266PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Li Z, Ramay HR, Hauch KD, Xiao D, Zhang M (2005) Chitosan-alginate hybrid scaffolds for bone tissue engineering. Biomaterials 26:3919–3928PubMedCrossRefGoogle Scholar
  62. 62.
    Kweon DK, Song SB, Park YY (2003) Preparation of water-soluble chitosan/heparin complex and its application as wound healing accelerator. Biomaterials 24:1595–1601PubMedCrossRefGoogle Scholar
  63. 63.
    Ueno H, Yamada H, Tanaka I, Kaba N, Matsuura M, Okumura M, Kadosawa T et al (1999) Accelerating effects of chitosan for healing at early phase of experimental open wound in dogs. Biomaterials 20:1407–1414PubMedCrossRefGoogle Scholar
  64. 64.
    Yu Y, Chen R, Sun Y, Pan Y, Tang W, Zhang S, Cao L et al (2018) Manipulation of VEGF-induced angiogenesis by 2-N, 6-O-sulfated chitosan. Acta Biomater 71:510–521PubMedCrossRefGoogle Scholar
  65. 65.
    Boucard N, Viton C, Agay D, Mari E, Roger T, Chancerelle Y, Domard A (2007) The use of physical hydrogels of chitosan for skin regeneration following third-degree burns. Biomaterials 28:3478–3488PubMedCrossRefGoogle Scholar
  66. 66.
    Thomas S (2000) Alginate dressings in surgery and wound management – part 1. J Wound Care 9:56–60PubMedCrossRefGoogle Scholar
  67. 67.
    Giri TK, Thakur D, Alexander A, Ajazuddin BH, Tripathi DK (2012) Alginate based hydrogel as a potential biopolymeric carrier for drug delivery and cell delivery systems: present status and applications. Curr Drug Deliv 9:539–555PubMedCrossRefGoogle Scholar
  68. 68.
    Wang Y, Miao Y, Zhang J, Wu JP, Kirk TB, Xu J, Ma D et al (2018) Three-dimensional printing of shape memory hydrogels with internal structure for drug delivery. Mater Sci Eng C Mater Biol Appl 84:44–51PubMedCrossRefGoogle Scholar
  69. 69.
    Smidsrod O, Skjak-Braek G (1990) Alginate as immobilization matrix for cells. Trends Biotechnol 8:71–78PubMedCrossRefGoogle Scholar
  70. 70.
    Gharravi AM, Orazizadeh M, Ansari-Asl K, Banoni S, Izadi S, Hashemitabar M (2012) Design and fabrication of anatomical bioreactor systems containing alginate scaffolds for cartilage tissue engineering. Avicenna J Med Biotechnol 4:65–74PubMedPubMedCentralGoogle Scholar
  71. 71.
    Beigi MH, Atefi A, Ghanaei HR, Labbaf S, Ejeian F, Nasr-Esfahani MH (2018) Activated platelet-rich plasma (PRP) improves cartilage regeneration using adipose stem cells encapsulated in a 3D alginate scaffold. J Tissue Eng Regen Med 12:1327–1338PubMedCrossRefGoogle Scholar
  72. 72.
    Coward SM, Legallais C, David B, Thomas M, Foo Y, Mavri-Damelin D, Hodgson HJ et al (2009) Alginate-encapsulated HepG2 cells in a fluidized bed bioreactor maintain function in human liver failure plasma. Artif Organs 33:1117–1126PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Yajima Y, Lee CN, Yamada M, Utoh R, Seki M (2018) Development of a perfusable 3D liver cell cultivation system via bundling-up assembly of cell-laden microfibers. J Biosci Bioeng 126:1111–1118PubMedCrossRefGoogle Scholar
  74. 74.
    Pipeleers D, Keymeulen B (2016) Boost for alginate encapsulation in Beta cell transplantation. Trends Endocrinol Metab 27:247–248PubMedCrossRefGoogle Scholar
  75. 75.
    Awad HA, Wickham MQ, Leddy HA, Gimble JM, Guilak F (2004) Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 25:3211–3222PubMedCrossRefGoogle Scholar
  76. 76.
    Gao M, Lu P, Bednark B, Lynam D, Conner JM, Sakamoto J, Tuszynski MH (2013) Templated agarose scaffolds for the support of motor axon regeneration into sites of complete spinal cord transection. Biomaterials 34:1529–1536PubMedCrossRefGoogle Scholar
  77. 77.
    Lynam DA, Shahriari D, Wolf KJ, Angart PA, Koffler J, Tuszynski MH, Chan C et al (2015) Brain derived neurotrophic factor release from layer-by-layer coated agarose nerve guidance scaffolds. Acta Biomater 18:128–131PubMedCrossRefGoogle Scholar
  78. 78.
    Zarrintaj P, Bakhshandeh B, Rezaeian I, Heshmatian B, Ganjali MR (2017) A novel electroactive agarose-aniline pentamer platform as a potential candidate for neural tissue engineering. Sci Rep 7:17187PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Han S, Lee JY, Heo EY, Kwon IK, Yune TY, Youn I (2018) Implantation of a matrigel-loaded agarose scaffold promotes functional regeneration of axons after spinal cord injury in rat. Biochem Biophys Res Commun 496:785–791PubMedCrossRefGoogle Scholar
  80. 80.
    Dahlmann J, Kensah G, Kempf H, Skvorc D, Gawol A, Elliott DA, Drager G et al (2013) The use of agarose microwells for scalable embryoid body formation and cardiac differentiation of human and murine pluripotent stem cells. Biomaterials 34:2463–2471PubMedCrossRefGoogle Scholar
  81. 81.
    Roosens A, Puype I, Cornelissen R (2017) Scaffold-free high throughput generation of quiescent valvular microtissues. J Mol Cell Cardiol 106:45–54PubMedCrossRefGoogle Scholar
  82. 82.
    Kim SS, Kang MS, Lee KY, Lee MJ, Wang L, Kim HJ (2012) Therapeutic effects of mesenchymal stem cells and hyaluronic acid injection on osteochondral defects in rabbits’ knees. Knee Surg Relat Res 24:164–172PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Migliore A, Procopio S (2015) Effectiveness and utility of hyaluronic acid in osteoarthritis. Clin Cases Miner Bone Metab 12:31–33PubMedPubMedCentralGoogle Scholar
  84. 84.
    Gold MH (2007) Use of hyaluronic acid fillers for the treatment of the aging face. Clin Interv Aging 2:369–376PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Yoo HS, Lee EA, Yoon JJ, Park TG (2005) Hyaluronic acid modified biodegradable scaffolds for cartilage tissue engineering. Biomaterials 26:1925–1933PubMedCrossRefGoogle Scholar
  86. 86.
    Davidenko N, Campbell JJ, Thian ES, Watson CJ, Cameron RE (2010) Collagen-hyaluronic acid scaffolds for adipose tissue engineering. Acta Biomater 6:3957–3968PubMedCrossRefGoogle Scholar
  87. 87.
    Kushchayev SV, Giers MB, Hom Eng D, Martirosyan NL, Eschbacher JM, Mortazavi MM, Theodore N et al (2016) Hyaluronic acid scaffold has a neuroprotective effect in hemisection spinal cord injury. J Neurosurg Spine 25:114–124PubMedCrossRefGoogle Scholar
  88. 88.
    Mano JF, Silva GA, Azevedo HS, Malafaya PB, Sousa RA, Silva SS, Boesel LF et al (2007) Natural origin biodegradable systems in tissue engineering and regenerative medicine: present status and some moving trends. J R Soc Interface 4:999–1030PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Lee C-T, Kung P-H, Lee Y-D (2005) Preparation of poly(vinyl alcohol)-chondroitin sulfate hydrogel as matrices in tissue engineering. Carbohydr Polym 61:348–354CrossRefGoogle Scholar
  90. 90.
    Bali JP, Cousse H, Neuzil E (2001) Biochemical basis of the pharmacologic action of chondroitin sulfates on the osteoarticular system. Semin Arthritis Rheum 31:58–68PubMedCrossRefGoogle Scholar
  91. 91.
    Henson FM, Getgood AM, Caborn DM, McIlwraith CW, Rushton N (2012) Effect of a solution of hyaluronic acid-chondroitin sulfate-N-acetyl glucosamine on the repair response of cartilage to single-impact load damage. Am J Vet Res 73:306–312PubMedCrossRefGoogle Scholar
  92. 92.
    Liang WH, Kienitz BL, Penick KJ, Welter JF, Zawodzinski TA, Baskaran H (2010) Concentrated collagen-chondroitin sulfate scaffolds for tissue engineering applications. J Biomed Mater Res A 94:1050–1060PubMedPubMedCentralGoogle Scholar
  93. 93.
    Zhou F, Zhang X, Cai D, Li J, Mu Q, Zhang W, Zhu S et al (2017) Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair. Acta Biomater 63:64–75PubMedCrossRefGoogle Scholar
  94. 94.
    Phillips TJ (1998) New skin for old: developments in biological skin substitutes. Arch Dermatol 134:344–349PubMedCrossRefGoogle Scholar
  95. 95.
    Macadam SA, Lennox PA (2012) Acellular dermal matrices: use in reconstructive and aesthetic breast surgery. Can J Plast Surg 20:75–89PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Chang J, DeLillo N Jr, Khan M, Nacinovich MR (2013) Review of small intestine submucosa extracellular matrix technology in multiple difficult-to-treat wound types. Wounds 25:113–120PubMedGoogle Scholar
  97. 97.
    Badylak SF (2004) Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl Immunol 12:367–377CrossRefGoogle Scholar
  98. 98.
    Voytik-Harbin SL, Brightman AO, Kraine MR, Waisner B, Badylak SF (1997) Identification of extractable growth factors from small intestinal submucosa. J Cell Biochem 67:478–491PubMedCrossRefGoogle Scholar
  99. 99.
    Chun SY, Lim GJ, Kwon TG, Kwak EK, Kim BW, Atala A, Yoo JJ (2007) Identification and characterization of bioactive factors in bladder submucosa matrix. Biomaterials 28:4251–4256PubMedCrossRefGoogle Scholar
  100. 100.
    Hodde JP, Record RD, Liang HA, Badylak SF (2001) Vascular endothelial growth factor in porcine-derived extracellular matrix. Endothelium 8:11–24PubMedCrossRefGoogle Scholar
  101. 101.
    Voytik-Harbin S, Brightman AO, Waisner B, Robinson J, Lamar CH (1998) Small intestinal submucosa: a tissue-derived extracellular matrix that promotes tissue-specific growth and differentiation of cells in vitro. Tissue Eng 4:157–174CrossRefGoogle Scholar
  102. 102.
    Lantz GC, Blevins WE, Badylak SF, Coffey AC, Geddes LA (1990) Small intestinal submucosa as a small-diameter arterial graft in the dog. J Investig Surg 3:217–227CrossRefGoogle Scholar
  103. 103.
    Lantz GC, Badylak SF, Coffey AC, Geddes LA, Sandusky GE (1992) Small intestinal submucosa as a superior vena cava graft in the dog. J Surg Res 53:175–181PubMedCrossRefGoogle Scholar
  104. 104.
    Kropp BP, Sawyer BD, Shannon HE, Rippy MK, Badylak SF, Adams MC, Keating MA et al (1996) Characterization of small intestinal submucosa regenerated canine detrusor: assessment of reinnervation, in vitro compliance and contractility. J Urol 156:599–607PubMedCrossRefGoogle Scholar
  105. 105.
    Kropp BP, Rippy MK, Badylak SF, Adams MC, Keating MA, Rink RC, Thor KB (1996) Regenerative urinary bladder augmentation using small intestinal submucosa: urodynamic and histopathologic assessment in long-term canine bladder augmentations. J Urol 155:2098–2104PubMedCrossRefGoogle Scholar
  106. 106.
    Gabouev AI, Schultheiss D, Mertsching H, Koppe M, Schlote N, Wefer J, Jonas U et al (2003) In vitro construction of urinary bladder wall using porcine primary cells reseeded on acellularized bladder matrix and small intestinal submucosa. Int J Artif Organs 26:935–942PubMedCrossRefGoogle Scholar
  107. 107.
    Fiala R, Vidlar A, Vrtal R, Belej K, Student V (2007) Porcine small intestinal submucosa graft for repair of anterior urethral strictures. Eur Urol 51:1702–1708 discussion 1708PubMedCrossRefGoogle Scholar
  108. 108.
    Albers P (2007) Tissue engineering and reconstructive surgery in urology. Eur Urol 52:1579PubMedCrossRefGoogle Scholar
  109. 109.
    Hoeppner J, Crnogorac V, Marjanovic G, Juttner E, Karcz W, Weiser HF, Hopt UT (2009) Small intestinal submucosa as a bioscaffold for tissue regeneration in defects of the colonic wall. J Gastrointest Surg 13:113–119PubMedCrossRefGoogle Scholar
  110. 110.
    Yi J-S, Lee H-J, Lee H-J, Lee I-W, Yang J-H (2013) Rat peripheral nerve regeneration using nerve guidance channel by porcine small intestinal submucosa. J Korean Neurosurg Soc 53:65–71PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Murphy F, Corbally MT (2007) The novel use of small intestinal submucosal matrix for chest wall reconstruction following Ewing’s tumour resection. Pediatr Surg Int 23:353–356PubMedCrossRefGoogle Scholar
  112. 112.
    Kumar V, Ahlawat R, Gupta AK, Sharma RK, Minz M, Sakhuja V, Jha V (2014) Potential of organ donation from deceased donors: study from a public sector hospital in India. Transpl Int 27:1007–1014PubMedCrossRefGoogle Scholar
  113. 113.
    Wainwright DJ (1995) Use of an acellular allograft dermal matrix (AlloDerm) in the management of full-thickness burns. Burns 21:243–248PubMedCrossRefGoogle Scholar
  114. 114.
    Bozuk MI, Fearing NM, Leggett PL (2006) Use of decellularized human skin to repair esophageal anastomotic leak in humans. JSLS 10:83–85PubMedPubMedCentralGoogle Scholar
  115. 115.
    Lin LM, Lin CC, Chen CL, Lin CC (2014) Effects of an education program on intensive care unit nurses’ attitudes and behavioral intentions to advocate deceased donor organ donation. Transplant Proc 46:1036–1040PubMedCrossRefGoogle Scholar
  116. 116.
    Rieder E, Seebacher G, Kasimir MT, Eichmair E, Winter B, Dekan B, Wolner E et al (2005) Tissue engineering of heart valves: decellularized porcine and human valve scaffolds differ importantly in residual potential to attract monocytic cells. Circulation 111:2792–2797PubMedCrossRefGoogle Scholar
  117. 117.
    Granados M, Morticelli L, Andriopoulou S, Kalozoumis P, Pflaum M, Iablonskii P, Glasmacher B et al (2017) Development and characterization of a porcine mitral valve scaffold for tissue engineering. J Cardiovasc Transl Res 10:374–390PubMedCrossRefGoogle Scholar
  118. 118.
    Rana D, Zreiqat H, Benkirane-Jessel N, Ramakrishna S, Ramalingam M (2017) Development of decellularized scaffolds for stem cell-driven tissue engineering. J Tissue Eng Regen Med 11:942–965PubMedCrossRefGoogle Scholar
  119. 119.
    Fang NT, Xie SZ, Wang SM, Gao HY, Wu CG, Pan LF (2007) Construction of tissue-engineered heart valves by using decellularized scaffolds and endothelial progenitor cells. Chin Med J 120:696–702PubMedGoogle Scholar
  120. 120.
    Jaramillo M, Yeh H, Yarmush ML, Uygun BE (2017) Decellularized human liver extracellular matrix (hDLM)-mediated hepatic differentiation of human induced pluripotent stem cells (hIPSCs). J Tissue Eng Regen Med 12:e1962–e1973CrossRefGoogle Scholar
  121. 121.
    Kakabadze Z, Kakabadze A, Chakhunashvili D, Karalashvili L, Berishvili E, Sharma Y, Gupta S (2017) Decellularized human placenta supports hepatic tissue and allows rescue in acute liver failure. Hepatology 67:1956–1969CrossRefGoogle Scholar
  122. 122.
    Kang YZ, Wang Y, Gao Y (2009) Decellularization technology application in whole liver reconstruct biological scaffold. Zhonghua Yi Xue Za Zhi 89:1135–1138PubMedGoogle Scholar
  123. 123.
    Arenas-Herrera JE, Ko IK, Atala A, Yoo JJ (2013) Decellularization for whole organ bioengineering. Biomed Mater 8:014106PubMedCrossRefGoogle Scholar
  124. 124.
    Baptista PM, Vyas D, Moran E, Wang Z, Soker S (2013) Human liver bioengineering using a whole liver decellularized bioscaffold. Methods Mol Biol 1001:289–298PubMedCrossRefGoogle Scholar
  125. 125.
    Ko IK, Peng L, Peloso A, Smith CJ, Dhal A, Deegan DB, Zimmerman C et al (2015) Bioengineered transplantable porcine livers with re-endothelialized vasculature. Biomaterials 40:72–79PubMedCrossRefGoogle Scholar
  126. 126.
    Mao SAGJ, Elgilani FM, De Lorenzo SB, Deeds MC et al (2017) Sustained in vivo perfusion of a re-endothelialized tissue engineered porcine liver. Int J nTransplant Res Med 3:031Google Scholar
  127. 127.
    Gilpin A, Yang Y (2017) Decellularization strategies for regenerative medicine: from processing techniques to applications. Biomed Res Int 2017:9831534PubMedPubMedCentralCrossRefGoogle Scholar
  128. 128.
    Sohlenius-Sternbeck AK (2006) Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements. Toxicol In Vitro 20:1582–1586PubMedCrossRefGoogle Scholar
  129. 129.
    Agmon G, Christman KL (2016) Controlling stem cell behavior with decellularized extracellular matrix scaffolds. Curr Opin Solid State Mater Sci 20:193–201PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Kadota Y, Yagi H, Inomata K, Matsubara K, Hibi T, Abe Y, Kitago M et al (2014) Mesenchymal stem cells support hepatocyte function in engineered liver grafts. Organogenesis 10:268–277PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Hoshiba T, Chen G, Endo C, Maruyama H, Wakui M, Nemoto E, Kawazoe N et al (2016) Decellularized extracellular matrix as an in vitro model to study the comprehensive roles of the ECM in stem cell differentiation. Stem Cells Int 2016:6397820PubMedCrossRefGoogle Scholar
  132. 132.
    Kim M, Choi B, Joo SY, Lee H, Lee JH, Lee KW, Lee S et al (2014) Generation of humanized liver mouse model by transplant of patient-derived fresh human hepatocytes. Transplant Proc 46:1186–1190PubMedCrossRefGoogle Scholar
  133. 133.
    Lee SY, Kim HJ, Choi D (2015) Cell sources, liver support systems and liver tissue engineering: alternatives to liver transplantation. Int J Stem Cells 8:36–47PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Nicolas C, Wang Y, Luebke-Wheeler J, Nyberg SL (2016) Stem cell therapies for treatment of liver disease. Biomedicine 4:E2CrossRefGoogle Scholar
  135. 135.
    AlZoubi AM, Khalifeh F (2013) The effectiveness of stem cell therapies on health-related quality of life and life expectancy in comparison with conventional supportive medical treatment in patients suffering from end-stage liver disease. Stem Cell Res Ther 4:16PubMedPubMedCentralCrossRefGoogle Scholar
  136. 136.
    Sauer V, Roy-Chowdhury N, Guha C, Roy-Chowdhury J (2014) Induced pluripotent stem cells as a source of hepatocytes. Curr Pathobiol Rep 2:11–20PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Moroni F, Mirabella T (2014) Decellularized matrices for cardiovascular tissue engineering. Am J Stem Cells 3:1–20PubMedPubMedCentralGoogle Scholar
  138. 138.
    Methe K, Backdahl H, Johansson BR, Nayakawde N, Dellgren G, Sumitran-Holgersson S (2014) An alternative approach to decellularize whole porcine heart. Biores Open Access 3:327–338PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Taylor DA, Sampaio LC, Gobin A (2014) Building new hearts: a review of trends in cardiac tissue engineering. Am J Transplant 14:2448–2459PubMedCrossRefGoogle Scholar
  140. 140.
    Weymann A, Loganathan S, Takahashi H, Schies C, Claus B, Hirschberg K, Soos P et al (2011) Development and evaluation of a perfusion decellularization porcine heart model – generation of 3-dimensional myocardial neoscaffolds. Circ J 75:852–860PubMedCrossRefGoogle Scholar
  141. 141.
    Manji RA, Menkis AH, Ekser B, Cooper DK (2012) Porcine bioprosthetic heart valves: the next generation. Am Heart J 164:177–185PubMedCrossRefGoogle Scholar
  142. 142.
    Taylor DA, Parikh RB, Sampaio LC (2017) Bioengineering hearts: simple yet complex. Curr Stem Cell Rep 3:35–44PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    Martins AM, Vunjak-Novakovic G, Reis RL (2014) The current status of iPS cells in cardiac research and their potential for tissue engineering and regenerative medicine. Stem Cell Rev 10:177–190PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Al-Awqati Q, Oliver JA (2002) Stem cells in the kidney. Kidney Int 61:387–395PubMedCrossRefGoogle Scholar
  145. 145.
    Bobulescu IA, Moe OW (2006) Na+/H+ exchangers in renal regulation of acid-base balance. Semin Nephrol 26:334–344PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Romagnani P, Remuzzi G, Glassock R, Levin A, Jager KJ, Tonelli M, Massy Z et al (2017) Chronic kidney disease. Nat Rev Dis Primers 3:17088CrossRefGoogle Scholar
  147. 147.
    Peired AJ, Sisti A, Romagnani P (2016) Mesenchymal stem cell-based therapy for kidney disease: a review of clinical evidence. Stem Cells Int 2016:4798639PubMedPubMedCentralGoogle Scholar
  148. 148.
    McKee RA, Wingert RA (2016) Repopulating decellularized kidney scaffolds: an avenue for ex vivo organ generation. Materials (Basel) 9:190CrossRefGoogle Scholar
  149. 149.
    Figliuzzi M, Bonandrini B, Remuzzi A (2017) Decellularized kidney matrix as functional material for whole organ tissue engineering. J Appl Biomater Funct Mater 15:0PubMedGoogle Scholar
  150. 150.
    Yu YL, Shao YK, Ding YQ, Lin KZ, Chen B, Zhang HZ, Zhao LN et al (2014) Decellularized kidney scaffold-mediated renal regeneration. Biomaterials 35:6822–6828PubMedCrossRefGoogle Scholar
  151. 151.
    Du C, Narayanan K, Leong MF, Ibrahim MS, Chua YP, Khoo VM, Wan AC (2016) Functional kidney bioengineering with pluripotent stem-cell-derived renal progenitor cells and decellularized kidney scaffolds. Adv Healthc Mater 5:2080–2091PubMedCrossRefGoogle Scholar
  152. 152.
    Yamanaka S, Yokoo T (2015) Current bioengineering methods for whole kidney regeneration. Stem Cells Int 2015:724047PubMedPubMedCentralCrossRefGoogle Scholar
  153. 153.
    Rawlins MD (2004) Cutting the cost of drug development? Nat Rev Drug Discov 3:360–364PubMedCrossRefGoogle Scholar
  154. 154.
    Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711–715PubMedCrossRefGoogle Scholar
  155. 155.
    Kaplowitz N (2005) Idiosyncratic drug hepatotoxicity. Nat Rev Drug Discov 4:489–499PubMedCrossRefGoogle Scholar
  156. 156.
    Rizzetto M, Ciancio A (2012) Epidemiology of hepatitis D. Semin Liver Dis 32:211–219PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
  158. 158.
    Smith BW, Adams LA (2011) Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol 7:456–465PubMedCrossRefGoogle Scholar
  159. 159.
    Cusi K (2009) Nonalcoholic fatty liver disease in type 2 diabetes mellitus. Curr Opin Endocrinol Diabetes Obes 16:141–149CrossRefPubMedGoogle Scholar
  160. 160.
    Koppe SWP (2014) Obesity and the liver: nonalcoholic fatty liver disease. Transl Res: J Lab Clin Med 164:312–322CrossRefGoogle Scholar
  161. 161.
    McGuire S (2016) World cancer report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO press, 2015. Adv Nutr (Bethesda, MD) 7:418–419CrossRefGoogle Scholar
  162. 162.
    LeCluyse EL, Witek RP, Andersen ME, Powers MJ (2012) Organotypic liver culture models: meeting current challenges in toxicity testing. Crit Rev Toxicol 42:501–548PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Gómez-Lechón MJ, Tolosa L, Conde I, Donato MT (2014) Competency of different cell models to predict human hepatotoxic drugs. Expert Opin Drug Metab Toxicol 10:1553–1568PubMedCrossRefGoogle Scholar
  164. 164.
    Hewitt NJ, Lechón MJG, Houston JB, Hallifax D, Brown HS, Maurel P, Kenna JG et al (2007) Primary hepatocytes: current understanding of the regulation of metabolic enzymes and transporter proteins, and pharmaceutical practice for the use of hepatocytes in metabolism, enzyme induction, transporter, clearance, and hepatotoxicity studies. Drug Metab Rev 39:159–234PubMedCrossRefGoogle Scholar
  165. 165.
    Rowe C, Goldring CEP, Kitteringham NR, Jenkins RE, Lane BS, Sanderson C, Elliott V et al (2010) Network analysis of primary hepatocyte dedifferentiation using a shotgun proteomics approach. J Proteome Res 9:2658–2668PubMedCrossRefGoogle Scholar
  166. 166.
    Bale SS, Golberg I, Jindal R, McCarty WJ, Luitje M, Hegde M, Bhushan A et al (2015) Long-term coculture strategies for primary hepatocytes and liver sinusoidal endothelial cells. Tissue Eng Part C Methods 21:413–422PubMedCrossRefGoogle Scholar
  167. 167.
    Krause P, Saghatolislam F, Koenig S, Unthan-Fechner K, Probst I (2009) Maintaining hepatocyte differentiation in vitro through co-culture with hepatic stellate cells. In Vitro Cell Dev Biol Anim 45:205–212PubMedCrossRefGoogle Scholar
  168. 168.
    Ohno M, Motojima K, Okano T, Taniguchi A (2008) Up-regulation of drug-metabolizing enzyme genes in layered co-culture of a human liver cell line and endothelial cells. Tissue Eng Part A 14:1861–1869PubMedCrossRefGoogle Scholar
  169. 169.
    Tukov FF, Maddox JF, Amacher DE, Bobrowski WF, Roth RA, Ganey PE (2006) Modeling inflammation-drug interactions in vitro: a rat Kupffer cell-hepatocyte coculture system. Toxicol In Vitro: An Int J Publ Assoc BIBRA 20:1488–1499CrossRefGoogle Scholar
  170. 170.
    Luebke-Wheeler JL, Nedredal G, Yee L, Amiot BP, Nyberg SL (2009) E-cadherin protects primary hepatocyte spheroids from cell death by a caspase-independent mechanism. Cell Transpl 18:1281–1287CrossRefGoogle Scholar
  171. 171.
    Sakai Y, Yamagami S, Nakazawa K (2010) Comparative analysis of gene expression in rat liver tissue and monolayer- and spheroid-cultured hepatocytes. Cells Tissues Organs 191:281–288CrossRefGoogle Scholar
  172. 172.
    Godoy P, Hewitt NJ, Albrecht U, Andersen ME, Ansari N, Bhattacharya S, Bode JG et al (2013) Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol 87:1315–1530PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Usta OB, McCarty WJ, Bale S, Hegde M, Jindal R, Bhushan A, Golberg I et al (2015) Microengineered cell and tissue systems for drug screening and toxicology applications: evolution of in-vitro liver technologies. Technology 3:1–26PubMedPubMedCentralCrossRefGoogle Scholar
  174. 174.
    Chan TS, Yu H, Moore A, Khetani SR, Kehtani SR, Tweedie D (2013) Meeting the challenge of predicting hepatic clearance of compounds slowly metabolized by cytochrome P450 using a novel hepatocyte model, HepatoPac. Drug Metab Dispos: The Biol Fate Chem 41:2024–2032CrossRefGoogle Scholar
  175. 175.
    Schütte J, Freudigmann C, Benz K, Böttger J, Gebhardt R, Stelzle M (2010) A method for patterned in situ biofunctionalization in injection-molded microfluidic devices. Lab Chip 10:2551–2558PubMedCrossRefGoogle Scholar
  176. 176.
    Baxter GT (2009) Hurel – an in vivo-surrogate assay platform for cell-based studies. Altern Lab Anim: ATLA 37(Suppl 1):11–18PubMedGoogle Scholar
  177. 177.
    Guillouzo A, Guguen-Guillouzo C (2008) Evolving concepts in liver tissue modeling and implications for in vitro toxicology. Expert Opin Drug Metab Toxicol 4:1279–1294PubMedCrossRefGoogle Scholar
  178. 178.
    Writing Group M, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al (2016) Heart disease and stroke statistics-2016 update: a report from the American heart association. Circulation:133:e38–360Google Scholar
  179. 179.
    Duan SZ, Usher MG, Mortensen RM (2008) Peroxisome proliferator-activated receptor-gamma-mediated effects in the vasculature. Circ Res 102:283–294PubMedCrossRefGoogle Scholar
  180. 180.
    Krentz A (2009) Thiazolidinediones: effects on the development and progression of type 2 diabetes and associated vascular complications. Diabetes Metab Res Rev 25:112–126PubMedCrossRefGoogle Scholar
  181. 181.
    Hernandez AV, Usmani A, Rajamanickam A, Moheet A (2011) Thiazolidinediones and risk of heart failure in patients with or at high risk of type 2 diabetes mellitus: a meta-analysis and meta-regression analysis of placebo-controlled randomized clinical trials. Am J Cardiovasc Drugs 11:115–128PubMedCrossRefGoogle Scholar
  182. 182.
    McNeish J (2004) Embryonic stem cells in drug discovery. Nat Rev Drug Discov 3:70–80PubMedCrossRefGoogle Scholar
  183. 183.
    Lu HR, Vlaminckx E, Hermans AN, Rohrbacher J, Van Ammel K, Towart R, Pugsley M et al (2008) Predicting drug-induced changes in QT interval and arrhythmias: QT-shortening drugs point to gaps in the ICHS7B guidelines. Br J Pharmacol 154:1427–1438PubMedPubMedCentralCrossRefGoogle Scholar
  184. 184.
    Redfern WS, Carlsson L, Davis AS, Lynch WG, MacKenzie I, Palethorpe S, Siegl PK et al (2003) Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 58:32–45PubMedCrossRefGoogle Scholar
  185. 185.
    Hoffmann P, Warner B (2006) Are hERG channel inhibition and QT interval prolongation all there is in drug-induced torsadogenesis? A review of emerging trends. J Pharmacol Toxicol Methods 53:87–105PubMedCrossRefGoogle Scholar
  186. 186.
    Lacerda AE, Kuryshev YA, Chen Y, Renganathan M, Eng H, Danthi SJ, Kramer JW et al (2008) Alfuzosin delays cardiac repolarization by a novel mechanism. J Pharmacol Exp Ther 324:427–433PubMedCrossRefGoogle Scholar
  187. 187.
    Rodriguez-Menchaca AA, Navarro-Polanco RA, Ferrer-Villada T, Rupp J, Sachse FB, Tristani-Firouzi M, Sanchez-Chapula JA (2008) The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel. Proc Natl Acad Sci U S A 105:1364–1368PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Pouton CW, Haynes JM (2007) Embryonic stem cells as a source of models for drug discovery. Nat Rev Drug Discov 6:605–616CrossRefGoogle Scholar
  189. 189.
    Braam SR, Tertoolen L, van de Stolpe A, Meyer T, Passier R, Mummery CL (2010) Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes. Stem Cell Res 4:107–116PubMedCrossRefGoogle Scholar
  190. 190.
    Zwi L, Caspi O, Arbel G, Huber I, Gepstein A, Park IH, Gepstein L (2009) Cardiomyocyte differentiation of human induced pluripotent stem cells. Circulation 120:1513–1523PubMedCrossRefGoogle Scholar
  191. 191.
    Otsuji TG, Minami I, Kurose Y, Yamauchi K, Tada M, Nakatsuji N (2010) Progressive maturation in contracting cardiomyocytes derived from human embryonic stem cells: qualitative effects on electrophysiological responses to drugs. Stem Cell Res 4:201–213PubMedCrossRefGoogle Scholar
  192. 192.
    Yoshida Y, Yamanaka S (2010) Recent stem cell advances: induced pluripotent stem cells for disease modeling and stem cell-based regeneration. Circulation 122:80–87PubMedCrossRefGoogle Scholar
  193. 193.
    Liang P, Lan F, Lee AS, Gong T, Sanchez-Freire V, Wang Y, Diecke S et al (2013) Drug screening using a library of human induced pluripotent stem cell-derived cardiomyocytes reveals disease-specific patterns of cardiotoxicity. Circulation 127:1677–1691PubMedCrossRefGoogle Scholar
  194. 194.
    Chen L, El-Sherif N, Boutjdir M (1999) Unitary current analysis of L-type Ca2+ channels in human fetal ventricular myocytes. J Cardiovasc Electrophysiol 10:692–700PubMedCrossRefGoogle Scholar
  195. 195.
    Eder A, Vollert I, Hansen A, Eschenhagen T (2016) Human engineered heart tissue as a model system for drug testing. Adv Drug Deliv Rev 96:214–224PubMedCrossRefGoogle Scholar
  196. 196.
    Nunes SS, Miklas JW, Liu J, Aschar-Sobbi R, Xiao Y, Zhang B, Jiang J et al (2013) Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes. Nat Methods 10:781–787PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Hansen A, Eder A, Bonstrup M, Flato M, Mewe M, Schaaf S, Aksehirlioglu B et al (2010) Development of a drug screening platform based on engineered heart tissue. Circ Res 107:35–44PubMedCrossRefGoogle Scholar
  198. 198.
    Campion S, Aubrecht J, Boekelheide K, Brewster DW, Vaidya VS, Anderson L, Burt D et al (2013) The current status of biomarkers for predicting toxicity. Expert Opin Drug Metab Toxicol 9:1391–1408PubMedCrossRefGoogle Scholar
  199. 199.
    Formentini I, Bobadilla M, Haefliger C, Hartmann G, Loghman-Adham M, Mizrahi J, Pomposiello S et al (2012) Current drug development challenges in chronic kidney disease (CKD) – identification of individualized determinants of renal progression and premature cardiovascular disease (CVD). Nephrol Dial Transplant 27(Suppl 3):iii81–iii88PubMedCrossRefGoogle Scholar
  200. 200.
    Miyata T, Kikuchi K, Kiyomoto H, van Ypersele de Strihou C (2011) New era for drug discovery and development in renal disease. Nat Rev Nephrol 7:469–477PubMedCrossRefGoogle Scholar
  201. 201.
    Prunotto M, Gabbiani G, Pomposiello S, Ghiggeri G, Moll S (2011) The kidney as a target organ in pharmaceutical research. Drug Discov Today 16:244–259PubMedCrossRefGoogle Scholar
  202. 202.
    Steimer A, Haltner E, Lehr CM (2005) Cell culture models of the respiratory tract relevant to pulmonary drug delivery. J Aerosol Med 18:137–182PubMedCrossRefGoogle Scholar
  203. 203.
    Klein SG, Serchi T, Hoffmann L, Blomeke B, Gutleb AC (2013) An improved 3D tetraculture system mimicking the cellular organisation at the alveolar barrier to study the potential toxic effects of particles on the lung. Part Fibre Toxicol 10:31PubMedPubMedCentralCrossRefGoogle Scholar
  204. 204.
    Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE (2010) Reconstituting organ-level lung functions on a chip. Science 328:1662–1668CrossRefGoogle Scholar
  205. 205.
    Barnes PJ, Bonini S, Seeger W, Belvisi MG, Ward B, Holmes A (2015) Barriers to new drug development in respiratory disease. Eur Respir J 45:1197–1207PubMedCrossRefGoogle Scholar
  206. 206.
    Lancaster MA, Knoblich JA (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:1247125CrossRefGoogle Scholar
  207. 207.
    Medvinsky A, Livesey FJ (2015) On human development: lessons from stem cell systems. Development 142:17–20PubMedCrossRefGoogle Scholar
  208. 208.
    Si-Tayeb K, Lemaigre FP, Duncan SA (2010) Organogenesis and development of the liver. Dev Cell 18:175–189PubMedCrossRefGoogle Scholar
  209. 209.
    Navarro-Alvarez N, Soto-Gutierrez A, Kobayashi N (2010) Hepatic stem cells and liver development. Methods Mol Biol 640:181–236PubMedCrossRefGoogle Scholar
  210. 210.
    Ader M, Tanaka EM (2014) Modeling human development in 3D culture. Curr Opin Cell Biol 31:23–28PubMedCrossRefGoogle Scholar
  211. 211.
    Chistiakov DA (2012) Liver regenerative medicine: advances and challenges. Cells Tissues Organs 196:291–312PubMedCrossRefGoogle Scholar
  212. 212.
    Wang Y, Cui CB, Yamauchi M, Miguez P, Roach M, Malavarca R, Costello MJ et al (2011) Lineage restriction of human hepatic stem cells to mature fates is made efficient by tissue-specific biomatrix scaffolds. Hepatology 53:293–305CrossRefGoogle Scholar
  213. 213.
    Vyas D, Baptista PM, Brovold M, Moran E, Gaston B, Booth C, Samuel M et al (2017) Self-assembled liver organoids recapitulate hepatobiliary organogenesis in vitro. Hepatology 67:750–761Google Scholar
  214. 214.
    Maher JJ, Bissell DM (1993) Cell-matrix interactions in liver. Semin Cell Biol 4:189–201PubMedCrossRefGoogle Scholar
  215. 215.
    Camp JG, Sekine K, Gerber T, Loeffler-Wirth H, Binder H, Gac M, Kanton S et al (2017) Multilineage communication regulates human liver bud development from pluripotency. Nature 546:533–538Google Scholar
  216. 216.
    Ma Z, Wang J, Loskill P, Huebsch N, Koo S, Svedlund FL, Marks NC et al (2015) Self-organizing human cardiac microchambers mediated by geometric confinement. Nat Commun 6:7413PubMedPubMedCentralCrossRefGoogle Scholar
  217. 217.
    Rosenblum ND (2008) Developmental biology of the human kidney. Semin Fetal Neonatal Med 13:125–132PubMedCrossRefGoogle Scholar
  218. 218.
    Reint G, Rak-Raszewska A, Vainio SJ (2017) Kidney development and perspectives for organ engineering. Cell Tissue Res 369:171–183PubMedCrossRefGoogle Scholar
  219. 219.
    Destefani AC, Sirtoli GM, Nogueira BV (2017) Advances in the knowledge about kidney decellularization and repopulation. Front Bioeng Biotechnol 5:34PubMedPubMedCentralCrossRefGoogle Scholar
  220. 220.
    Kaminski MM, Tosic J, Kresbach C, Engel H, Klockenbusch J, Muller AL, Pichler R et al (2016) Direct reprogramming of fibroblasts into renal tubular epithelial cells by defined transcription factors. Nat Cell Biol 18:1269–1280PubMedCrossRefGoogle Scholar
  221. 221.
    Abolbashari M, Agcaoili SM, Lee MK, Ko IK, Aboushwareb T, Jackson JD, Yoo JJ et al (2016) Repopulation of porcine kidney scaffold using porcine primary renal cells. Acta Biomater 29:52–61PubMedCrossRefGoogle Scholar
  222. 222.
    Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC (2013) Regeneration and experimental orthotopic transplantation of a bioengineered kidney. Nat Med 19:646–651PubMedPubMedCentralCrossRefGoogle Scholar
  223. 223.
    Taguchi A, Kaku Y, Ohmori T, Sharmin S, Ogawa M, Sasaki H, Nishinakamura R (2014) Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells. Cell Stem Cell 14:53–67CrossRefGoogle Scholar
  224. 224.
    Dye BR, Miller AJ, Spence JR (2016) How to grow a lung: applying principles of developmental biology to generate lung lineages from human pluripotent stem cells. Curr Pathobiol Rep 4:47–57PubMedPubMedCentralCrossRefGoogle Scholar
  225. 225.
    Metzger RJ, Klein OD, Martin GR, Krasnow MA (2008) The branching programme of mouse lung development. Nature 453:745–750PubMedPubMedCentralCrossRefGoogle Scholar
  226. 226.
    Herriges M, Morrisey EE (2014) Lung development: orchestrating the generation and regeneration of a complex organ. Development 141:502–513PubMedPubMedCentralCrossRefGoogle Scholar
  227. 227.
    Miller AJ, Spence JR (2017) In vitro models to study human lung development, disease and homeostasis. Physiology (Bethesda) 32:246–260Google Scholar
  228. 228.
    Rock JR, Onaitis MW, Rawlins EL, Lu Y, Clark CP, Xue Y, Randell SH et al (2009) Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A 106:12771–12775PubMedPubMedCentralCrossRefGoogle Scholar
  229. 229.
    Ghaedi M, Calle EA, Mendez JJ, Gard AL, Balestrini J, Booth A, Bove PF et al (2013) Human iPS cell-derived alveolar epithelium repopulates lung extracellular matrix. J Clin Invest 123:4950–4962PubMedPubMedCentralCrossRefGoogle Scholar
  230. 230.
    Dye BR, Hill DR, Ferguson MA, Tsai YH, Nagy MS, Dyal R, Wells JM et al (2015) In vitro generation of human pluripotent stem cell derived lung organoids. elife 4:e05098Google Scholar
  231. 231.
    Murphy SV, Atala A (2014) 3D bioprinting of tissues and organs. Nat Biotechnol 32:773–785PubMedPubMedCentralCrossRefGoogle Scholar
  232. 232.
    Klein GT, Lu Y, Wang MY (2013) 3D printing and neurosurgery – ready for prime time? World Neurosurg 80:233–235PubMedCrossRefGoogle Scholar
  233. 233.
    Ozbolat IT, Yu Y (2013) Bioprinting toward organ fabrication: challenges and future trends. IEEE Trans Biomed Eng 60:691–699PubMedCrossRefGoogle Scholar
  234. 234.
    Cui X, Boland T, D’Lima DD, Lotz MK (2012) Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat Drug Deliv Formul 6:149–155PubMedPubMedCentralCrossRefGoogle Scholar
  235. 235.
    Zhang YS, Yue K, Aleman J, Mollazadeh-Moghaddam K, Bakht SM, Yang J, Jia W et al (2017) 3D bioprinting for tissue and organ fabrication. Ann Biomed Eng 45:148–163PubMedCrossRefGoogle Scholar
  236. 236.
    Jana S, Tefft BJ, Spoon DB, Simari RD (2014) Scaffolds for tissue engineering of cardiac valves. Acta Biomater 10:2877–2893PubMedCrossRefGoogle Scholar
  237. 237.
    Chambers J (2014) Prosthetic heart valves. Int J Clin Pract 68:1227–1230PubMedCrossRefGoogle Scholar
  238. 238.
    Sodian R, Weber S, Markert M, Rassoulian D, Kaczmarek I, Lueth TC, Reichart B et al (2007) Stereolithographic models for surgical planning in congenital heart surgery. Ann Thorac Surg 83:1854–1857PubMedCrossRefGoogle Scholar
  239. 239.
    Sodian R, Schmauss D, Markert M, Weber S, Nikolaou K, Haeberle S, Vogt F et al (2008) Three-dimensional printing creates models for surgical planning of aortic valve replacement after previous coronary bypass grafting. Ann Thorac Surg 85:2105–2108PubMedCrossRefGoogle Scholar
  240. 240.
    Sodian R, Weber S, Markert M, Loeff M, Lueth T, Weis FC, Daebritz S et al (2008) Pediatric cardiac transplantation: three-dimensional printing of anatomic models for surgical planning of heart transplantation in patients with univentricular heart. J Thorac Cardiovasc Surg 136:1098–1099PubMedCrossRefGoogle Scholar
  241. 241.
    Sodian R, Schmauss D, Schmitz C, Bigdeli A, Haeberle S, Schmoeckel M, Markert M et al (2009) 3-dimensional printing of models to create custom-made devices for coil embolization of an anastomotic leak after aortic arch replacement. Ann Thorac Surg 88:974–978PubMedCrossRefGoogle Scholar
  242. 242.
    Schmauss D, Schmitz C, Bigdeli AK, Weber S, Gerber N, Beiras-Fernandez A, Schwarz F et al (2012) Three-dimensional printing of models for preoperative planning and simulation of transcatheter valve replacement. Ann Thorac Surg 93:e31–e33PubMedCrossRefGoogle Scholar
  243. 243.
    Schmauss D, Gerber N, Sodian R (2013) Three-dimensional printing of models for surgical planning in patients with primary cardiac tumors. J Thorac Cardiovasc Surg 145:1407–1408PubMedCrossRefGoogle Scholar
  244. 244.
    Sodian R, Loebe M, Hein A, Martin DP, Hoerstrup SP, Potapov EV, Hausmann H et al (2002) Application of stereolithography for scaffold fabrication for tissue engineered heart valves. ASAIO J 48:12–16PubMedCrossRefGoogle Scholar
  245. 245.
    Schaefermeier PK, Szymanski D, Weiss F, Fu P, Lueth T, Schmitz C, Meiser BM et al (2009) Design and fabrication of three-dimensional scaffolds for tissue engineering of human heart valves. Eur Surg Res 42:49–53PubMedCrossRefGoogle Scholar
  246. 246.
    Duan B, Hockaday LA, Kang KH, Butcher JT (2013) 3D bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels. J Biomed Mater Res A 101:1255–1264PubMedCrossRefGoogle Scholar
  247. 247.
    Duan B, Kapetanovic E, Hockaday LA, Butcher JT (2014) Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells. Acta Biomater 10:1836–1846CrossRefPubMedGoogle Scholar
  248. 248.
    Cohen S, Leor J (2004) Rebuilding broken hearts. Biologists and engineers working together in the fledgling field of tissue engineering are within reach of one of their greatest goals: constructing a living human heart patch. Sci Am 291:44–51PubMedCrossRefGoogle Scholar
  249. 249.
    Silvestri A, Boffito M, Sartori S, Ciardelli G (2013) Biomimetic materials and scaffolds for myocardial tissue regeneration. Macromol Biosci 13:984–1019PubMedCrossRefGoogle Scholar
  250. 250.
    Cho GS, Fernandez L, Kwon C (2014) Regenerative medicine for the heart: perspectives on stem-cell therapy. Antioxid Redox Signal 21:2018–2031PubMedPubMedCentralCrossRefGoogle Scholar
  251. 251.
    Radisic M, Malda J, Epping E, Geng W, Langer R, Vunjak-Novakovic G (2006) Oxygen gradients correlate with cell density and cell viability in engineered cardiac tissue. Biotechnol Bioeng 93:332–343PubMedCrossRefGoogle Scholar
  252. 252.
    Yeong WY, Sudarmadji N, Yu HY, Chua CK, Leong KF, Venkatraman SS, Boey YC et al (2010) Porous polycaprolactone scaffold for cardiac tissue engineering fabricated by selective laser sintering. Acta Biomater 6:2028–2034CrossRefPubMedGoogle Scholar
  253. 253.
    Gaetani R, Doevendans PA, Metz CH, Alblas J, Messina E, Giacomello A, Sluijter JP (2012) Cardiac tissue engineering using tissue printing technology and human cardiac progenitor cells. Biomaterials 33:1782–1790CrossRefPubMedGoogle Scholar
  254. 254.
    Pati F, Jang J, Ha DH, Won Kim S, Rhie JW, Shim JH, Kim DH et al (2014) Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun 5:3935PubMedPubMedCentralCrossRefGoogle Scholar
  255. 255.
    Homan KA, Kolesky DB, Skylar-Scott MA, Herrmann J, Obuobi H, Moisan A, Lewis JA (2016) Bioprinting of 3D convoluted renal proximal tubules on perfusable chips. Sci Rep 6:34845PubMedPubMedCentralCrossRefGoogle Scholar
  256. 256.
    Horvath L, Umehara Y, Jud C, Blank F, Petri-Fink A, Rothen-Rutishauser B (2015) Engineering an in vitro air-blood barrier by 3D bioprinting. Sci Rep 5:7974PubMedPubMedCentralCrossRefGoogle Scholar
  257. 257.
    Badawy A, Hamaguchi Y, Satoru S, Kaido T, Okajima H, Uemoto S (2017) Evaluation of safety of concomitant splenectomy in living donor liver transplantation: a retrospective study. Transpl Int 30:914–923PubMedCrossRefGoogle Scholar
  258. 258.
    Athanasiou A, Papalois A, Kontos M, Griniatsos J, Liakopoulos D, Spartalis E, Agrogiannis G et al (2017) The beneficial role of simultaneous splenectomy after extended hepatectomy: experimental study in pigs. J Surg Res 208:121–131PubMedCrossRefGoogle Scholar
  259. 259.
    Troisi RI, Berardi G, Tomassini F, Sainz-Barriga M (2017) Graft inflow modulation in adult-to-adult living donor liver transplantation: a systematic review. Transplant Rev (Orlando) 31:127–135CrossRefGoogle Scholar
  260. 260.
    Okabe H, Yoshizumi T, Ikegami T, Uchiyama H, Harimoto N, Itoh S, Kimura K et al (2016) Salvage splenic artery embolization for saving falling living donor graft due to portal overflow: a case report. Transplant Proc 48:3171–3173PubMedCrossRefGoogle Scholar
  261. 261.
    Scatton O, Cauchy F, Conti F, Perdigao F, Massault PP, Goumard C, Soubrane O (2016) Two-stage liver transplantation using auxiliary laparoscopically harvested grafts in adults: emphasizing the concept of “hypersmall graft nursing”. Clin Res Hepatol Gastroenterol 40:571–574PubMedCrossRefGoogle Scholar
  262. 262.
  263. 263.
    Kinaci E, Kayaalp C (2017) Systematic review for small-for-size syndrome after liver transplantation-chamber of secrets: reply. World J Surg 41:343–344PubMedCrossRefGoogle Scholar
  264. 264.
    Salman A, El-Garem N, Sholkamy A, Hosny K, Abdelaziz O (2016) Exploring portal vein hemodynamic velocities as a promising, attractive horizon for small-for-size syndrome prediction after living-donor liver transplantation: an egyptian center study. Transplant Proc 48:2135–2139PubMedCrossRefGoogle Scholar
  265. 265.
    Ikegami T, Yoshizumi T, Sakata K, Uchiyama H, Harimoto N, Harada N, Itoh S et al (2016) Left lobe living donor liver transplantation in adults: what is the safety limit? Liver Transpl 22:1666–1675PubMedCrossRefGoogle Scholar
  266. 266.
    Ito D, Akamatsu N, Togashi J, Kaneko J, Arita J, Hasegawa K, Sakamoto Y et al (2016) Behavior and clinical impact of ascites after living donor liver transplantation: risk factors associated with massive ascites. J Hepatobiliary Pancreat Sci 23:688–696PubMedCrossRefGoogle Scholar
  267. 267.
    Halazun KJ, Przybyszewski EM, Griesemer AD, Cherqui D, Michelassi F, Guarrera JV, Kato T et al (2016) Leaning to the left: increasing the donor pool by using the left lobe, outcomes of the largest single-center north american experience of left lobe adult-to-adult living donor liver transplantation. Ann Surg 264:448–456PubMedCrossRefGoogle Scholar
  268. 268.
    Pomposelli JJ, Goodrich NP, Emond JC, Humar A, Baker TB, Grant DR, Fisher RA et al (2016) Patterns of early allograft dysfunction in adult live donor liver transplantation: the a2all experience. Transplantation 100:1490–1499PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Matthew Brovold
    • 1
  • Joana I. Almeida
    • 2
  • Iris Pla-Palacín
    • 2
  • Pilar Sainz-Arnal
    • 2
    • 3
  • Natalia Sánchez-Romero
    • 2
  • Jesus J. Rivas
    • 2
  • Helen Almeida
    • 2
  • Pablo Royo Dachary
    • 4
    • 5
  • Trinidad Serrano-Aulló
    • 4
    • 5
  • Shay Soker
    • 1
    Email author
  • Pedro M. Baptista
    • 4
    • 6
    • 7
    • 8
    • 9
    Email author
  1. 1.Wake Forest Institute for Regenerative MedicineWinston-SalemUSA
  2. 2.Health Research Institute of Aragón (IIS Aragón)ZaragozaSpain
  3. 3.Aragon Health Sciences Institute (IACS)ZaragozaSpain
  4. 4.Instituto de Investigación Sanitária de Aragón (IIS Aragón)ZaragozaSpain
  5. 5.Liver Transplant Unit, Gastroenterology DepartmentLozano Blesa University HospitalZaragozaSpain
  6. 6.Center for Biomedical Research Network Liver and Digestive Diseases (CIBERehd)ZaragozaSpain
  7. 7.Instituto de Investigación Sanitaria de la Fundación Jiménez DíazMadridSpain
  8. 8.Biomedical and Aerospace Engineering DepartmentUniversidad Carlos III de MadridMadridSpain
  9. 9.Fundación ARAIDZaragozaSpain

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