Three-Dimensional Bioprinting Scaffolding for Nasal Cartilage Defects: A Systematic Review



In recent years, three-dimensional (3D)-printing of tissue-engineered cartilaginous scaffolds is intended to close the surgical gap and provide bio-printed tissue designed to fit the specific geometric and functional requirements of each cartilage defect, avoiding donor site morbidity and offering a personalizing therapy.


To investigate the role of 3D—bioprinting scaffolding for nasal cartilage defects repair a systematic review of the electronic databases for 3D-Bioprinting articles pertaining to nasal cartilage bio-modelling was performed. The primary focus was to investigate cellular source, type of scaffold utilization, biochemical evaluation, histological analysis, in-vitro study, in-vivo study, animal model used, length of research, and placement of experimental construct and translational investigation.


From 1011 publications, 16 studies were kept for analysis. About cellular sources described, most studies used primary chondrocyte cultures. The cartilage used for cell isolation was mostly nasal septum. The most common biomaterial used for scaffold creation was polycaprolactone alone or in combination. About mechanical evaluation, we found a high heterogeneity, making it difficult to extract any solid conclusion. Regarding biological and histological characteristics of each scaffold, we found that the expression of collagen type I, collagen Type II and other ECM components were the most common patterns evaluated through immunohistochemistry on in-vitro and in-vivo studies. Only two studies made an orthotopic placement of the scaffolds. However, in none of the studies analyzed, the scaffold was placed in a subperichondrial pocket to rigorously simulate the cartilage environment. In contrast, scaffolds were implanted in a subcutaneous plane in almost all of the studies included.


The role of 3D—bioprinting scaffolding for nasal cartilage defects repair is growing field. Despite the amount of information collected in the last years and the first surgical applications described recently in humans. Further investigations are needed due to the heterogeneity on mechanical evaluation parameters, the high level of heterotopic scaffold implantation and the need for quantitative histological data.

This is a preview of subscription content, access via your institution.

Fig. 1


  1. 1.

    Hull CW. Inventor; Uvp Inc., original assignee. Apparatus for production of three-dimensional objects by stereolithography. US Patent US4575330A (1986). Accessed 11 Oct 2020.

  2. 2.

    Kruth JP, Leu MC, Nakagawa T. Progress in additive manufacturing and rapid prototyping. CIRP Ann Manuf Technol. 1998;47:525–40.

    Article  Google Scholar 

  3. 3.

    Melchels FP, Domingos MA, Klein TJ, Malda J, Bartolo PJ, Hutmacher DW. Additive manufacturing of tissues and organs. Prog Polym Sci. 2012;37:1079–104.

    CAS  Article  Google Scholar 

  4. 4.

    Bak D. Rapid prototyping or rapid production? 3D printing processes move industry towards the latter. Assem Autom. 2003;23:340–5.

    Article  Google Scholar 

  5. 5.

    Setton LA, Elliott DM, Mow VC. Altered mechanics of cartilage with osteoarthritis: human osteoarthritis and an experimental model of joint degeneration. Osteoarthritis Cartilage. 1999;7:2–14.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Jackson DW, Scheer MJ, Simon TM. Cartilage substitutes: overview of basic science and treatment options. J Am Acad Orthop Surg. 2001;9:37–52.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Rengier F, Mehndiratta A, von Tengg-Kobligk H, Zechmann CM, Unterhinninghofen R, Kauczor HU, et al. 3D printing based on imaging data: review of medical applications. Int J Comput Assist Radiol Surg. 2010;5:335–41.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Kushnaryov A, Yamaguchi T, Briggs K, Reuther MS, Watson D, Masuda K, et al. Evaluation of autogenous engineered septal cartilage grafts in rabbits: a minimally invasive preclinical model. Otolaryngol Head Neck Surg. 2013;149:37–8.

    Article  Google Scholar 

  9. 9.

    Fulco I, Miot S, Haug MD, Barbero A, Wixmerten A, Feliciano S, et al. Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial. Lancet. 2014;384:337–46.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Niermeyer WL, Rodman C, Li MM, Chiang T. Tissue engineering applications in otolaryngology-the state of translation. Laryngoscope Investig Otolaryngol. 2020;5:630–48.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA group. preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    OCEBM Levels of Evidence Working Group. “The Oxford 2011 levels of evidence.” Oxford centre for evidence-based medicine. 2011.

  13. 13.

    Wei D, Tang K, Wang Q, Estill J, Yao L, Wang X, et al. The use of GRADE approach in systematic reviews of animal studies. J Evid Based Med. 2016;9:98–104.

    PubMed  Article  Google Scholar 

  14. 14.

    Shafiee A, Seyedjafari E, Sadat Taherzadeh E, Dinarvand P, Soleimani M, Ai J. Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds. Mater Sci Eng C Mater Biol Appl. 2014;40:445–54.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Zopf DA, Mitsak AG, Flanagan CL, Wheeler M, Green GE, Hollister SJ. Computer aided-designed, 3-dimensionally printed porous tissue bioscaffolds for craniofacial soft tissue reconstruction. Otolaryngol Head Neck Surg. 2015;152:57–62.

    PubMed  Article  Google Scholar 

  16. 16.

    Xu Y, Fan F, Kang N, Wang S, You J, Wang H, et al. Tissue engineering of human nasal alar cartilage precisely by using three-dimensional printing. Plast Reconstr Surg. 2015;135:451–8.

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Kim YS, Shin YS, Park DY, Choi JW, Park JK, Kim DH, et al. The application of three-dimensional printing in animal model of augmentation rhinoplasty. Ann Biomed Eng. 2015;43:2153–62.

    PubMed  Article  Google Scholar 

  18. 18.

    Park SH, Yun BG, Won JY, Yun WS, Shim JH, Lim MH, et al. New application of three-dimensional printing biomaterial in nasal reconstruction. Laryngoscope. 2017;127:1036–43.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Möller T, Amoroso M, Hägg D, Brantsing C, Rotter N, Apelgren P, et al. In vivo chondrogenesis in 3D bioprinted human cell-laden hydrogel constructs. Plast Reconstr Surg Glob Open. 2017;5:e1227.

    PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Apelgren P, Amoroso M, Lindahl A, Brantsing C, Rotter N, Gatenholm P, et al. Chondrocytes and stem cells in 3D-bioprinted structures create human cartilage in vivo. PLoS One. 2017;12:e0189428.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  21. 21.

    Rajzer I, Kurowska A, Jabłoński A, Jatteau S, Śliwka M, Ziąbka M, et al. Layered gelatin/PLLA scaffolds fabricated by electrospinning and 3D printing- for nasal cartilages and subchondral bone reconstruction. Mater Des. 2018;155:297–306.

    CAS  Article  Google Scholar 

  22. 22.

    Morrison RJ, Nasser HB, Kashlan KN, Zopf DA, Milner DJ, Flanangan CL, et al. Co-culture of adipose-derived stem cells and chondrocytes on three-dimensionally printed bioscaffolds for craniofacial cartilage engineering. Laryngoscope. 2018;128:E251–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Kim DH, Lim MH, Jeun JH, Park SH, Lee W, Park SH, et al. Evaluation of polycaprolactone-associated human nasal chondrocytes as a therapeutic agent for cartilage repair. Tissue Eng Regen Med. 2019;16:605–14.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Xia H, Zhao D, Zhu H, Hua Y, Xiao K, Xu Y, et al. Lyophilized scaffolds fabricated from 3D-printed photocurable natural hydrogel for cartilage regeneration. ACS Appl Mater Interfaces. 2018;10:31704–15.

    CAS  PubMed  Article  Google Scholar 

  25. 25.

    Wiggenhauser PS, Schwarz S, Koerber L, Hoffmann TK, Rotter N. Addition of decellularized extracellular matrix of porcine nasal cartilage improves cartilage regenerative capacities of PCL-based scaffolds in vitro. J Mater Sci Mater Med. 2019;30:121.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Yi HG, Choi YJ, Jung JW, Jang J, Song TH, Chae S, et al. Three-dimensional printing of a patient-specific engineered nasal cartilage for augmentative rhinoplasty. J Tissue Eng. 2019;10:2041731418824797.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  27. 27.

    Kim DH, Yun WS, Shim JH, Park KH, Choi D, Park MI, et al. Clinical application of 3-dimensional printing technology for patients with nasal septal deformities: a multicenter study. JAMA Otolaryngol Head Neck Surg. 2018;144:1145–52.

    PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Ruiz-Cantu L, Gleadall A, Faris C, Segal J, Shakesheff K, Yang J. Multi-material 3D bioprinting of porous constructs for cartilage regeneration. Mater Sci Eng C Mater Biol Appl. 2020;109:110578.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Rajzer I, Kurowska A, Jabłoński A, Kwiatkowski R, Piekarczyk W, Hajduga MB, et al. Scaffolds modified with graphene as future implants for nasal cartilage. J Mater Sci. 2020;55:4030–42.

    CAS  Article  Google Scholar 

  30. 30.

    Jodat YA, Kiaee K, Vela Jarquin D, De la Garza Hernández RL, Wang T, Joshi S, et al. A 3D-printed hybrid nasal cartilage with functional electronic olfaction. Adv Sci (Weinh). 2020;7:1901878.

    CAS  PubMed Central  Article  PubMed  Google Scholar 

  31. 31.

    Dhandayuthapani B, Yoshida Y, Maekawa T, Kumar DS. Polymeric scaffolds in tissue engineering application: a review. Int J Polym Sci. 2011;2011:290602.

    Article  Google Scholar 

  32. 32.

    Atala A. Tissue engineering of reproductive tissues and organs. Fertil Steril. 2012;98:21–9.

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Forbes SJ, Rosenthal N. Preparing the ground for tissue regeneration: from mechanism to therapy. Nat Med. 2014;20:857–69.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  34. 34.

    Lindahl A. From gristle to chondrocyte transplantation: treatment of cartilage injuries. Philos Trans R Soc Lond B Biol Sci. 2015;370:20140369.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  35. 35.

    Brent B. The correction of mi-rotia with autogenous cartilage grafts: I. The classic deformity. Plast Reconstr Surg. 1980;66:1–12.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  36. 36.

    Firmin F. State-of-the-art autogenous ear reconstruction in cases of microtia. In: Staudenmaier R, editor. Aesthetics and functionality in ear reconstruction. Basel: Karger Publishers; 2010. p. 25–52.

    Google Scholar 

  37. 37.

    Zopf DA, Iams W, Kim JC, Baker SR, Moyer JS. Full-thickness skin graft overlying a separately harvested auricular cartilage graft for nasal alar reconstruction. JAMA Facial Plast Surg. 2013;15:131–4.

    PubMed  Article  Google Scholar 

  38. 38.

    Firmin F, Marchac A. A novel algorithm for autologous ear reconstruction. Semin Plast Surg. 2011;25:257–64.

    PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Osorno G. Autogenous rib cartilage reconstruction of congenital ear defects: report of 110 cases with Brent’s technique. Plast Reconstr Surg. 1999;104:1951–62.

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Romo T 3rd, Presti PM, Yalamanchili HR. Medpor alternative for microtia repair. Facial Plast Surg Clin North Am. 2006;14:129–36.

    PubMed  Article  Google Scholar 

  41. 41.

    Zhao YY, Zhuang HX, Jiang HY, Jiang WJ, Hu XG, Hu SD, et al. Clinical application of three methods for total ear reconstruction. Zhonghua Zheng Xing Wai Ke Za Zhi. 2008;24:287–90.

    PubMed  PubMed Central  Google Scholar 

  42. 42.

    Tian H, Tang Z, Zhuang X, Chen X, Jing X. Biodegradable synthetic polymers: preparation, functionalization and biomedical application. Prog Polym Sci. 2012;37:237–80.

    CAS  Article  Google Scholar 

  43. 43.

    O’Brien FJ. Biomaterials and scaffolds for tissue engineering. Mater Today (Kidlington). 2011;14:88–95.

    Article  CAS  Google Scholar 

  44. 44.

    Bose S, Vahabzadeh S, Bandyopadhyay A. Bone tissue engineering using 3D printing. Mater Today (Kidlington). 2013;16:496–504.

    CAS  Article  Google Scholar 

  45. 45.

    Gauvin R, Chen YC, Lee JW, Soman P, Zorlutuna P, Nichol JW, et al. Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography. Biomaterials. 2012;33:3824–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Martin JR, Gupta MK, Page JM, Yu F, Davidson JM, Guelcher SA, et al. A porous tissue engineering scaffold selectively degraded by cell-generated reactive oxygen species. Biomaterials. 2014;35:3766–76.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Teh TK, Toh SL, Goh JC. Aligned hybrid silk scaffold for enhanced differentiation of mesenchymal stem cells into ligament fibroblasts. Tissue Eng Part C Methods. 2011;17:687–703.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Unadkat HV, Hulsman M, Cornelissen K, Papenburg BJ, Truckenmüller RK, Carpenter AE, et al. An algorithm-based topographical biomaterials library to instruct cell fate. Proc Natl Acad Sci U S A. 2011;108:16565–70.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Thomas V, Jose MV, Chowdhury S, Sullivan JF, Dean DR, Vohra YK. Mechano-morphological studies of aligned nanofibrous scaffolds of polycaprolactone fabricated by electrospinning. J Biomater Sci Polym Ed. 2006;17:969–84.

    CAS  PubMed  Article  Google Scholar 

  50. 50.

    Bedi A, Feeley BT, Williams RJ 3rd. Management of articular cartilage defects of the knee. J Bone Joint Surg Am. 2010;92:994–1009.

    PubMed  Article  Google Scholar 

  51. 51.

    Discher DE, Janmey P, Wang YL. Tissue cells feel and respond to the stiffness of their substrate. Science. 2005;310:1139–43.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Homicz MR, McGowan KB, Lottman LM, Beh G, Sah RL, Watson D. A compositional analysis of human nasal septal cartilage. Arch Facial Plast Surg. 2003;5:53–8.

    PubMed  Article  Google Scholar 

  53. 53.

    Bas O, De-Juan-Pardo EM, Meinert C, D’Angella D, Baldwin JG, Bray LJ, et al. Biofabricated soft network composites for cartilage tissue engineering. Biofabrication. 2017;9:025014.

    PubMed  Article  CAS  Google Scholar 

  54. 54.

    Kafienah W, Jakob M, Démarteau O, Frazer A, Barker MD, Martin I, et al. Three-dimensional tissue engineering of hyaline cartilage: comparison of adult nasal and articular chondrocytes. Tissue Eng. 2002;8:817–26.

    CAS  PubMed  Article  Google Scholar 

  55. 55.

    Rotter N, Bonassar LJ, Tobias G, Lebl M, Roy AK, Vacanti CA. Age dependence of biochemical and biomechanical properties of tissue-engineered human septal cartilage. Biomaterials. 2002;23:3087–94.

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    Tay AG, Farhadi J, Suetterlin R, Pierer G, Heberer M, Martin I. Cell yield, proliferation, and postexpansion differentiation capacity of human ear, nasal, and rib chondrocytes. Tissue Eng. 2004;10:762–70.

    PubMed  Article  Google Scholar 

  57. 57.

    Liu X, Sun H, Yan D, Zhang L, Lv X, Liu T, et al. In vivo ectopic chondrogenesis of BMSCs directed by mature chondrocytes. Biomaterials. 2010;31:9406–14.

    CAS  PubMed  Article  Google Scholar 

  58. 58.

    Keller B, Yang T, Chen Y, Munivez E, Bertin T, Zabel B, et al. Interaction of TGFbeta and BMP signaling pathways during chondrogenesis. PLoS One. 2011;6:e316421.

    Google Scholar 

  59. 59.

    Kim JS, Ryoo ZY, Chun JS. Cytokine-like 1 (Cytl1) regulates the chondrogenesis of mesenchymal cells. J Biol Chem. 2007;282:29359–67.

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Choi YS, Lim SM, Shin HC, Lee CW, Kim SL, Kim DI. Chondrogenesis of human periostiumderived progenitor cells in atelocollagen. Biotechnol Lett. 2007;29:323–9.

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Mo XT, Guo SC, Xie HQ, Deng L, Zhi W, Xiang Z, et al. Variations in the ratios of co-cultured mesenchymal stem cells and chondrocytes regulate the expression of cartilaginous and osseous phenotype in alginate constructs. Bone. 2009;45:42–51.

    PubMed  Article  Google Scholar 

  62. 62.

    Shieh SJ, Terada S, Vacanti JP. Tissue engineering auricular reconstruction: in vitro and in vivo studies. Biomaterials. 2004;25:1545–57.

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Zhou L, Pomerantseva I, Bassett EK, Bowley CM, Zhao X, Bichara DA, et al. Engineering ear constructs with a composite scaffold to maintain dimensions. Tissue Eng Part A. 2011;17:1573–81.

    CAS  PubMed  Article  Google Scholar 

  64. 64.

    Xue J, Feng B, Zheng R, Lu Y, Zhou G, Liu W, et al. Engineering earshaped cartilage using electrospun fibrous membranes of gelatin/polycaprolactone. Biomaterials. 2013;34:2624–31.

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Ruszymah BH, Chua KH, Mazlyzam AL, Aminuddin BS. Formation of tissue engineered composite construct of cartilage and skin using high density polyethylene as inner scaffold in the shape of human helix. Int J Pediatr Otorhinolaryngol. 2011;75:805–10.

    CAS  PubMed  Article  Google Scholar 

  66. 66.

    Yanaga H, Imai K, Fujimoto T, Yanaga K. Generating ears from cultured autologous auricular chondrocytes by using two-stage implantation in treatment of microtia. Plast Reconstr Surg. 2009;124:817–25.

    CAS  PubMed  Article  Google Scholar 

  67. 67.

    von der Mark K, Gauss V, von der Mark H, Müller P. Relationship between cell shape and type of collagen synthesised as chondrocytes lose their cartilage phenotype in culture. Nature. 1977;267:531–2.

    PubMed  Article  Google Scholar 

  68. 68.

    Kusuhara H, Isogai N, Enjo M, Otani H, Ikada Y, Jacquet R, et al. Tissue engineering a model for the human ear: assessment of size, shape, morphology, and gene expression following seeding of different chondrocytes. Wound Repair Regen. 2009;17:136–46.

    PubMed  Article  Google Scholar 

  69. 69.

    Tsutsumi S, Shimazu A, Miyazaki K, Pan H, Koike C, Yoshida E, et al. Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun. 2001;288:413–9.

    CAS  PubMed  Article  Google Scholar 

  70. 70.

    Martin I, Shastri VP, Padera RF, Yang J, Mackay AJ, Langer R, et al. Selective differentiation of mammalian bone marrow stromal cells cultured on three-dimensional polymer foams. J Biomed Mater Res. 2001;55:229–35.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  71. 71.

    Hwang NS, Elisseeff J. Application of stem cells for articular cartilage regeneration. J Knee Surg. 2009;22:60–71.

    PubMed  Article  Google Scholar 

  72. 72.

    Hickok NJ, Haas AR, Tuan RS. Regulation of chondrocyte differentiation and maturation. Microsc Res Tech. 1998;43:174–90.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  73. 73.

    Merceron C, Vinatier C, Portron S, Masson M, Amiaud J, Guigand L, et al. Differential effects of hypoxia on osteochondrogenic potential of human adipose-derived stem cells. Am J Physiol Cell Physiol. 2010;298:C355–64.

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Zhang L, Hu J, Athanasiou KA. The role of tissue engineering in articular cartilage repair and regeneration. Crit Rev Biomed Eng. 2009;37:1–57.

    PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Ferril GR, Wudel JM, Winkler AA. Management of complications from alloplastic implants in rhinoplasty. Curr Opin Otolaryngol Head Neck Surg. 2013;21:372–8.

    PubMed  Google Scholar 

  76. 76.

    Glasgold MJ, Kato YP, Christiansen D, Hauge JA, Glasgold AI, Silver FH. Mechanical properties of septal cartilage homografts. Otolaryngol Head Neck Surg. 1988;99:374–9.

    CAS  PubMed  Article  Google Scholar 

  77. 77.

    Li X, Cui R, Sun L, Aifantis KE, Fan Y, Feng Q, et al. 3D-printed biopolymers for tissue engineering application. Int J Polym Sci. 2014;2014:829145.

    CAS  Article  Google Scholar 

  78. 78.

    Dang JM, Leong KW. Natural polymers for gene delivery and tissue engineering. Adv Drug Deliv Rev. 2006;58:487–99.

    CAS  PubMed  Article  Google Scholar 

  79. 79.

    Liu M, Zeng X, Ma C, Yi H, Ali Z, Mou X, et al. Injectable hydrogels for cartilage and bone tissue engineering. Bone Res. 2017;5:17014.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  80. 80.

    Wiggenhauser PS, Schantz JT, Rotter N. Cartilage engineering in reconstructive surgery: auricular, nasal and tracheal engineering from a surgical perspective. Regen Med. 2017;12:303–14.

    CAS  PubMed  Article  Google Scholar 

  81. 81.

    Elsaesser AF, Bermueller C, Schwarz S, Koerber L, Breiter R, Rotter N. In vitro cytotoxicity and in vivo effects of a decellularized xenogeneic collagen scaffold in nasal cartilage repair. Tissue Eng Part A. 2014;20:1668–78.

    CAS  PubMed  Article  Google Scholar 

  82. 82.

    Goldberg-Bockhorn E, Schwarz S, Elsässer A, Seitz A, Körber L, Dürselen L, et al. Physical characterization of decellularized cartilage matrix for reconstructive rhinosurgery. Laryngorhinootologie. 2014;93:756–63.

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Schwarz S, Elsaesser AF, Koerber L, Goldberg-Bockhorn E, Seitz AM, Bermueller C, et al. Processed xenogenic cartilage as innovative biomatrix for cartilage tissue engineering: effects on chondrocyte differentiation and function. J Tissue Eng Regen Med. 2015;9:E239–51.

    CAS  PubMed  Article  Google Scholar 

  84. 84.

    Schwarz S, Koerber L, Elsaesser AF, Goldberg-Bockhorn E, Seitz AM, Durselen L, et al. Decellularized cartilage matrix as a novel biomatrix for cartilage tissue-engineering applications. Tissue Eng Part A. 2012;18:2195–209.

    CAS  PubMed  Article  Google Scholar 

  85. 85.

    Guillotin B, Guillemot F. Cell patterning technologies for organotypic tissue fabrication. Trends Biotechnol. 2011;29:183–90.

    CAS  PubMed  Article  Google Scholar 

  86. 86.

    Frampton JP, Hynd MR, Shuler ML, Shain W. Fabrication and optimization of alginate hydrogel constructs for use in 3D neural cell culture. Biomed Mater. 2011;6:015002.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  87. 87.

    Martínez Ávila H, Feldmann EM, Pleumeekers MM, Nimeskern L, Kuo W, de Jong WC, et al. Novel bilayer bacterial nanocellulose scaffold supports neocartilage formation in vitro and in vivo. Biomaterials. 2015;44:122–33.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  88. 88.

    Wu L, Leijten JC, Georgi N, Post JN, van Blitterswijk CA, Karperien M. Trophic effects of mesenchymal stem cells increase chondrocyte proliferation and matrix formation. Tissue Eng Part A. 2011;17:1425–36.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  89. 89.

    Zuo Q, Cui W, Liu F, Wang Q, Chen Z, Fan W. Co-cultivated mesenchymal stem cells support chondrocytic differentiation of articular chondrocytes. Int Orthop. 2013;37:747–52.

    PubMed  PubMed Central  Article  Google Scholar 

  90. 90.

    Wu L, Prins HJ, Helder MN, van Blitterswijk CA, Karperien M. Trophic effects of mesenchymal stem cells in chondrocyte co-cultures are independent of culture conditions and cell sources. Tissue Eng Part A. 2012;18:1542–51.

    CAS  PubMed  Article  Google Scholar 

  91. 91.

    de Windt TS, Hendriks JA, Zhao X, Vonk LA, Creemers LB, Dhert WJ, et al. Concise review: unraveling stem cell cocultures in regenerative medicine: which cell interactions steer cartilage regeneration and how? Stem Cells Transl Med. 2014;3:723–33.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  92. 92.

    Leijten JC, Georgi N, Wu L, van Blitterswijk CA, Karperien M. Cell sources for articular cartilage repair strategies: shifting from monocultures to cocultures. Tissue Eng Part B Rev. 2013;19:31–40.

    CAS  PubMed  Article  Google Scholar 

  93. 93.

    Chiesa-Estomba C, González-Fernández I, Iglesias-Otero M. 3D printing for biomedical applications: where arewe now? Eur Med J. 2017;2:16–22.

    Google Scholar 

Download references


Conceptualization, C.M.C.E. and A.A.; methodology, C.M.C.E.; validation, A.I., X.A. and I.G.; formal analysis, C.M.C.E. and R.H; investigation, C.R. and A.D.; data curation, J.P. and J.A; writing—original draft preparation, C.M.C.E.; writing—review and editing, C.M.C.E.; supervision. All authors have read and agreed to the published version of the manuscript.

Author information



Corresponding author

Correspondence to Carlos M. Chiesa-Estomba.

Ethics declarations

Conflict of interest

The authors declares that they don’t have any conflict of interest.

Ethical statement

There are no animal experiments carried out for this article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chiesa-Estomba, C.M., Aiastui, A., González-Fernández, I. et al. Three-Dimensional Bioprinting Scaffolding for Nasal Cartilage Defects: A Systematic Review. Tissue Eng Regen Med (2021).

Download citation


  • Cartilage
  • Nasal
  • Bioprinting
  • Chondrocytes
  • Polycaprolactone