Skip to main content

The Application of Cartilage Tissue Engineering with Cell-Laden Hydrogel in Plastic Surgery: A Systematic Review



As a contour-supporting material, the cartilage has a significant application value in plastic surgery. Since the development of hydrogel scaffolds with sufficient biomechanical strength and high biocompatibility, cell-laden hydrogels have been widely studied for application in cartilage bioengineering. This systematic review summarizes the latest research on engineered cartilage constructed using cell-laden hydrogel scaffolds in plastic surgery.


A systematic review was performed by searching the PubMed and Web of Science databases using selected keywords and Medical Subject Headings search terms.


Forty-two studies were identified based on the search criteria. After full-text screening for inclusion and exclusion criteria, 18 studies were included. Data collected from each study included culturing form, seed cell types and sources, concentration of cells and gels, scaffold materials and bio-printing structures, and biomechanical properties of cartilage constructs. These cell-laden hydrogel scaffolds were reported to show some feasibility of cartilage engineering, including better cell proliferation, enhanced deposition of glycosaminoglycans and collagen type II in the extracellular matrix, and better biomechanical properties close to the natural state.


Cell-laden hydrogels have been widely used in cartilage bioengineering research. Through 3-dimensional (3D) printing, the cell-laden hydrogel can form a bionic contour structure. Extracellular matrix expression was observed in vivo and in vitro, and the elastic modulus was reported to be similar to that of natural cartilage. The future direction of cartilage tissue engineering in plastic surgery involves the use of novel hydrogel materials and more advanced 3D printing technology combined with biochemistry and biomechanical stimulation.

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

Fig. 1


  1. 1.

    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  Article  Google Scholar 

  2. 2.

    Daniel RK. Rhinoplasty: dorsal grafts and the designer dorsum. Clinics Plast Surg. 2010;37:293–300.

    Article  Google Scholar 

  3. 3.

    Zhou F, Hong Y, Zhang X, Yang L, Li J, Jiang D, et al. Tough hydrogel with enhanced tissue integration and in situ forming capability for osteochondral defect repair. Appl Mater Today. 2018;13:32–44.

  4. 4.

    Yang J, Zhang YS, Yue K, Khademhosseini A. Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta Biomater. 2017;57:1–25.

    CAS  Article  Google Scholar 

  5. 5.

    Tanaka Y, Yamaoka H, Nishizawa S, Nagata S, Ogasawara T, Asawa Y, et al. The optimization of porous polymeric scaffolds for chondrocyte/atelocollagen based tissue-engineered cartilage. Biomaterials. 2010;31:4506–16.

  6. 6.

    Bichara DA, Zhao X, Hwang NS, Bodugoz-Senturk H, Yaremchuk MJ, Randolph MA, et al. Porous poly(vinyl alcohol)-alginate gel hybrid construct for neocartilage formation using human nasoseptal cells. J Surg Res. 2010;163:331–6.

  7. 7.

    Reiffel AJ, Kafka C, Hernandez KA, Popa S, Perez JL, Zhou S, et al. High-fidelity tissue engineering of patient-specific auricles for reconstruction of pediatric microtia and other auricular deformities. PloS One. 2013;8:e56506.

  8. 8.

    Chen CH, Shyu VB, Chen JP, Lee MY. Selective laser sintered poly-epsilon-caprolactone scaffold hybridized with collagen hydrogel for cartilage tissue engineering. Biofabrication. 2014;6:015004.

    CAS  Article  Google Scholar 

  9. 9.

    Cohen BP, Hooper RC, Puetzer JL, Nordberg R, Asanbe O, Hernandez KA, et al. Long-term morphological and microarchitectural stability of tissue-engineered, patient-specific auricles in vivo. Tissue Eng Part A. 2016;22:461–8.

  10. 10.

    Zopf DA, Flanagan CL, Mitsak AG, Brennan JR, Hollister SJ. Pore architecture effects on chondrogenic potential of patient-specific 3-dimensionally printed porous tissue bioscaffolds for auricular tissue engineering. Int J Pediatr Otorhinolaryngol. 2018;114:170–4.

    Article  Google Scholar 

  11. 11.

    Visscher DO, Gleadall A, Buskermolen JK, Burla F, Segal J, Koenderink GH, et al. Design and fabrication of a hybrid alginate hydrogel/poly(epsilon-caprolactone) mold for auricular cartilage reconstruction. J Biomed Mater Res B Appl Biomater. 2019;107:1711–21.

  12. 12.

    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  Article  Google Scholar 

  13. 13.

    Xu Y, Xu Y, Bi B, Hou M, Yao L, Du Q, et al. A moldable thermosensitive hydroxypropyl chitin hydrogel for 3D cartilage regeneration in vitro and in vivo. Acta Biomater. 2020;108:87–96.

  14. 14.

    Visscher DO, Lee H, van Zuijlen PPM, Helder MN, Atala A, Yoo JJ, et al. A photo-crosslinkable cartilage-derived extracellular matrix bioink for auricular cartilage tissue engineering. Acta Biomater. 2021;121:193–203.

  15. 15.

    Otto IA, Levato R, Webb WR, Khan IM, Breugem CC, Malda J. Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture. Eur Cell Mater. 2018;35:132–50.

    CAS  Article  Google Scholar 

  16. 16.

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

  17. 17.

    Visscher DO, Bos EJ, Peeters M, Kuzmin NV, Groot ML, Helder MN, et al. Cartilage tissue engineering: preventing tissue scaffold contraction using a 3D-printed polymeric cage. Tissue Eng Part C Methods. 2016;22:573–84.

  18. 18.

    Morrison KA, Cohen BP, Asanbe O, Dong X, Harper A, Bonassar LJ, et al. Optimizing cell sourcing for clinical translation of tissue engineered ears. Biofabrication. 2016;9:015004.

  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.

  20. 20.

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

  21. 21.

    Chang CS, Yang CY, Hsiao HY, Chen L, Chu IM, Cheng MH, et al. Cultivation of auricular chondrocytes in poly(ethylene glycol)/poly(epsilon-caprolactone) hydrogel for tracheal cartilage tissue engineering in a rabbit model. Eur Cell Mater. 2018;35:350–64.

  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.

  23. 23.

    Li D, An Y, Yang X. An overview of asian rhinoplasty. Ann Plast Surg. 2016;77:S22-4.

    CAS  Article  Google Scholar 

  24. 24.

    Idone F. Diced cartilage grafts wrapped in rectus abdominis fascia for nasal dorsum augmentation. Plast Reconstr Surg. 2016;138:762e.

    CAS  Article  Google Scholar 

  25. 25

    Storck K, Staudenmaier R, Buchberger M, Strenger T, Kreutzer K, von Bomhard A, et al. Total reconstruction of the auricle: our experiences on indications and recent techniques. Biomed Res Int. 2014;2014:373286.

  26. 26.

    Nagata S. A new method of total reconstruction of the auricle for microtia. Plast Reconstr Surg. 1993;92:187–201.

    CAS  Article  Google Scholar 

  27. 27.

    Liao J, Chen Y, Chen J, He B, Qian L, Xu J, et al. Auricle shaping using 3D printing and autologous diced cartilage. Laryngoscope. 2019;129:2467–74.

  28. 28.

    Eke G, Mangir N, Hasirci N, MacNeil S, Hasirci V. Development of a UV crosslinked biodegradable hydrogel containing adipose derived stem cells to promote vascularization for skin wounds and tissue engineering. Biomaterials. 2017;129:188–98.

    CAS  Article  Google Scholar 

  29. 29.

    Lam T, Dehne T, Krüger JP, Hondke S, Endres M, Thomas A, et al. Photopolymerizable gelatin and hyaluronic acid for stereolithographic 3D bioprinting of tissue-engineered cartilage. J Biomed Mater Res B Appl Biomater. 2019;107:2649–57.

  30. 30.

    Nemeth CL, Janebodin K, Yuan AE, Dennis JE, Reyes M, Kim DH. Enhanced chondrogenic differentiation of dental pulp stem cells using nanopatterned PEG-GelMA-HA hydrogels. Tissue Eng Part A. 2014;20:2817–29.

    CAS  Article  Google Scholar 

  31. 31.

    Boere KW, Visser J, Seyednejad H, Rahimian S, Gawlitta D, van Steenbergen MJ, et al. Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs. Acta Biomater. 2014;10:2602–11.

  32. 32.

    Shi W, Sun M, Hu X, Ren B, Cheng J, Li C, et al. Structurally and functionally optimized silk-fibroin-gelatin scaffold using 3d printing to repair cartilage injury in vitro and in vivo. Adv Mater. 2017.

  33. 33.

    Levett PA, Melchels FP, Schrobback K, Hutmacher DW, Malda J, Klein TJ. A biomimetic extracellular matrix for cartilage tissue engineering centered on photocurable gelatin, hyaluronic acid and chondroitin sulfate. Acta Biomater. 2014;10:214–23.

  34. 34.

    Yue K, Trujillo-de Santiago G, Alvarez MM, Tamayol A, Annabi N, Khademhosseini A. Synthesis, properties, and biomedical applications of gelatin methacryloyl (GelMA) hydrogels. Biomaterials. 2015;73:254–71.

    CAS  Article  Google Scholar 

  35. 35.

    Ma Q, Liao J, Cai X. Different sources of stem cells and their application in cartilage tissue engineering. Curr Stem Cell Res Ther. 2018;13:568–75.

    CAS  Article  Google Scholar 

  36. 36.

    You Q, Liu Z, Zhang J, Shen M, Li Y, Jin Y, et al. Human amniotic mesenchymal stem cell sheets encapsulating cartilage particles facilitate repair of rabbit osteochondral defects. Am J Sports Med. 2020;48:599–611.

  37. 37.

    Veronesi F, Maglio M, Tschon M, Aldini NN, Fini M. Adipose-derived mesenchymal stem cells for cartilage tissue engineering: state-of-the-art in in vivo studies. J Biomed Mater Res A. 2014;102:2448–66.

    Article  Google Scholar 

  38. 38.

    Bexkens R, Ogink PT, Doornberg JN, Kerkhoffs GMMJ, Eygendaal D, Oh LS, et al. Donor-site morbidity after osteochondral autologous transplantation for osteochondritis dissecans of the capitellum: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2017;25:2237–46.

  39. 39.

    Hurley ET, Yasui Y, Gianakos AL, Seow D, Shimozono Y, Kerkhoffs GMMJ, et al. Limited evidence for adipose-derived stem cell therapy on the treatment of osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2018;26:3499–507.

  40. 40.

    Scioli MG, Bielli A, Gentile P, Cervelli V, Orlandi A. Combined treatment with platelet-rich plasma and insulin favours chondrogenic and osteogenic differentiation of human adipose-derived stem cells in three-dimensional collagen scaffolds. J Tissue Eng Regen Med. 2017;11:2398–410.

    CAS  Article  Google Scholar 

  41. 41.

    Yang Q, Teng BH, Wang LN, Li K, Xu C, Ma XL, et al. Silk fibroin/cartilage extracellular matrix scaffolds with sequential delivery of TGF-beta 3 for chondrogenic differentiation of adipose-derived stem cells. Int J Nanomedicine. 2017;12:6721–33.

  42. 42.

    Cho H, Kim J, Kim S, Jung YC, Wang Y, Kang BJ, et al. Dual delivery of stem cells and insulin-like growth factor-1 in coacervate-embedded composite hydrogels for enhanced cartilage regeneration in osteochondral defects. J Control Release. 2020;327:284–95.

  43. 43.

    Deng ZH, Li YS, Gao X, Lei GH, Huard J. Bone morphogenetic proteins for articular cartilage regeneration. Osteoarthritis Cartilage. 2018;26:1153–61.

    CAS  Article  Google Scholar 

  44. 44.

    Chen Y, Ma M, Teng Y, Cao H, Yang Y, Wang Y, et al. Efficient manufacturing of tissue engineered cartilage in vitro by a multiplexed 3D cultured method. J Mater Chem B. 2020;8:2082–95.

  45. 45.

    De Moor L, Fernandez S, Vercruysse C, Tytgat L, Asadian M, De Geyter N, et al. Hybrid bioprinting of chondrogenically induced human mesenchymal stem cell spheroids. Front Bioeng Biotechnol. 2020;8:484.

  46. 46.

    Vainieri ML, Lolli A, Kops N, D'Atri D, Eglin D, Yayon A, et al. Evaluation of biomimetic hyaluronic-based hydrogels with enhanced endogenous cell recruitment and cartilage matrix formation. Acta Biomater. 2020;101:293–303.

  47. 47.

    Hao J, Zhang Y, Jing D, Shen Y, Tang G, Huang S, et al. Mechanobiology of mesenchymal stem cells: perspective into mechanical induction of MSC fate. Acta Biomater. 2015;20:1–9.

  48. 48.

    Huebsch N, Arany PR, Mao AS, Shvartsman D, Ali OA, Bencherif SA, et al. Harnessing traction-mediated manipulation of the cell/matrix interface to control stem-cell fate. Nat Mater. 2010;9:518–26.

  49. 49.

    Khetan S, Guvendiren M, Legant WR, Cohen DM, Chen CS, Burdick JA. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat Mater. 2013;12:458–65.

    CAS  Article  Google Scholar 

  50. 50.

    Sen B, Xie Z, Case N, Ma M, Rubin C, Rubin J. Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal. Endocrinology. 2008;149:6065–75.

    CAS  Article  Google Scholar 

  51. 51.

    Lee J, Abdeen AA, Zhang D, Kilian KA. Directing stem cell fate on hydrogel substrates by controlling cell geometry, matrix mechanics and adhesion ligand composition. Biomaterials. 2013;34:8140–8.

    CAS  Article  Google Scholar 

  52. 52.

    Dalby MJ, Gadegaard N, Tare R, Andar A, Riehle MO, Herzyk P, et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat Mater. 2007;6:997–1003.

  53. 53.

    Liao S, Nguyen LT, Ngiam M, Wang C, Cheng Z, Chan CK, et al. Biomimetic nanocomposites to control osteogenic differentiation of human mesenchymal stem cells. Adv Healthc Mater. 2014;3:737–51.

  54. 54.

    Kilian KA, Bugarija B, Lahn BT, Mrksich M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc Nat Acad Sci U S A. 2010;107:4872–7.

    CAS  Article  Google Scholar 

  55. 55

    Zhang ZZ, Chen YR, Wang SJ, Zhao F, Wang XG, Yang F, et al. Orchestrated biomechanical structural and biochemical stimuli for engineering anisotropic meniscus. Sci Transl Med. 2019;11:eaao0750.

Download references


This article was funded by China Postdoctoral Science Foundation with the number of 2020M670001ZX.

Author information



Corresponding authors

Correspondence to Hongsen Bi or Zhenmin Zhao.

Ethics declarations

Conflict of interest

The authors declare 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

Wang, G., Zhang, X., Bu, X. et al. The Application of Cartilage Tissue Engineering with Cell-Laden Hydrogel in Plastic Surgery: A Systematic Review. Tissue Eng Regen Med (2021).

Download citation


  • 3D bioprinting
  • Tissue engineering
  • Cartilage
  • Cell-laden hydrogel
  • Plastic surgery