Skip to main content
SpringerLink
Log in

Combining Diced Cartilage with Chondrocyte Spheroids in GelMA Hydrogel: An Animal Study in Diced Cartilage Grafting Technique

  • Original Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

BACKGROUND:

The phenotype maintenance of diced cartilage is a very important factor to reduce cartilage absorption rate in augmentation rhinoplasty. A novel method which combined diced cartilage with chondrocyte spheroids in gelatin methacrylate (GelMA) hydrogel may have potentially good performance in phenotype maintenance, and is worth exploring.

METHODS:

The complex grafts formed by loading diced cartilage with chondrocyte spheroids into GelMA hydrogel were used as the experimental group, and the grafts formed of diced cartilage in GelMA were used as the control group. The two groups of grafts were implanted subcutaneously in nude mice. After 1 month and 3 months, the grafts were taken for general observation and histological analysis. The diameter changes of cartilage, the nuclei loss of chondrocyte, and glycosaminoglycan secretion were analyzed.

RESULTS:

Chondrocyte spheroids with obvious proliferation can be seen in the experimental group. Some diced cartilages had become a whole through the interconnection of chondrocyte spheroids. In addition, the diameter of the chondrocyte spheroids—diced cartilage complex in the experimental group increased significantly, and its nuclei loss rate was less than 1/2 of that in the control group. The maintenance of proteoglycans in diced cartilages in the experimental group was significantly better than that in the control group.

CONCLUSION:

The combination of diced cartilage with chondrocyte spheroids in GelMA hydrogel can significantly reduce the absorption of cartilage extracellular matrix, enhance phenotype maintenance during subcutaneous ectopic implantation, and can produce inter-chondral connections.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Yoo SH, Jang YJ. Rib cartilage in Asian rhinoplasty: new trends. Curr Opin Otolaryngol Head Neck Surg. 2019;27:261–6.

    Article  Google Scholar 

  2. Na HG, Jang YJ. Dorsal augmentation using alloplastic implants. Facial Plast Surg. 2017;33:189–94.

    Article  CAS  Google Scholar 

  3. Kridel RWH, Sturm AK. Dorsal augmentation with homologous rib. Facial Plast Surg. 2017;33:195–201.

    Article  CAS  Google Scholar 

  4. Li J, Sang C, Fu R, Liu C, Suo L, Yan Y, et al. Long-term complications from diced cartilage in rhinoplasty: a meta-analysis. Facial Plast Surg Aesthet Med. 2022;24:221–7.

    Article  Google Scholar 

  5. Firat C, Gurlek A, Aydin NE. Viability of cartilage grafts in various forms. J Craniofac Surg. 2013;24:530–530.

    Google Scholar 

  6. Tasman AJ, Diener PA, Litschel R. The diced cartilage glue graft for nasal augmentation morphometric evidence of longevity. JAMA Facial Plast Surg. 2013;15:86–94.

    Article  Google Scholar 

  7. Campiglio G, Rafanelli G, Klinger F, Caviggioli F, Giannasi S, Klinger M. Dorsal augmentation with diced conchal cartilage wrapped in retroauricular fascia. Aesthetic Plast Surg. 2019;43:780–5.

    Article  PubMed  Google Scholar 

  8. Robotti E, Leone F. The SPF-SPLF graft: building the ideal dorsum in revision rhinoplasty. Plast Reconstr Surg. 2020;145:1420–4.

    Article  CAS  PubMed  Google Scholar 

  9. Kemaloglu CA, Tekin Y. A comparison of diced cartilage grafts wrapped in perichondrium versus fascia. Aesthetic Plast Surg. 2014;38:1164–8.

    Article  Google Scholar 

  10. Ashtiani AK, Moghimi MR, Hafezi F. Perichondrial attached diced cartilage (PADC), a novel graft material for nasal augmentation: 10 years of experience. Aesthet Surg J. 2022;42:NP11–9.

    Article  Google Scholar 

  11. Hapsari NP, Bangun K, Atmodiwirjo P, Ponco B, Dewi TIT, Halim J. The effect of perichondrium and graft modification on the viability of conchal cartilage graft: an experimental study in rabbit. Cleft Palate Craniofac J. 2022;59:149–55.

    Article  Google Scholar 

  12. Shi Y, Guo R, Hou Q, Hu H, Wang H, Jiang H. The effect of perichondrium on biological and biomechanical properties of molded diced cartilage grafts. Aesthetic Plast Surg. 2020;44:549–57.

    Article  Google Scholar 

  13. Liao JL, Chen J, He B, Chen Y, Xu JQ, Xie HJ, et al. Viability and biomechanics of diced cartilage blended with platelet-rich plasma and wrapped with poly (lactic-co-glycolic) acid membrane. J Craniofac Surg. 2017;28:1418–24.

    Article  PubMed  Google Scholar 

  14. Guler I, Billur D, Aydin S, Kocaturk S. Efficacy of platelet-rich fibrin matrix on viability of diced cartilage grafts in a rabbit model. Laryngoscope. 2015;125:E104–11.

    Article  PubMed  Google Scholar 

  15. Yin H, Xie C, Li L, Zeng L, Zhu ZW, Chen N, et al. Effect of stromal vascular fractions on angiogenesis of injected diced cartilage. J Craniofac Surg. 2022;33:713–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Topkara A, Özkan A, Özcan RH, Öksüz M, Akbulut M. Effect of concentrated growth factor on survival of diced cartilage graft. Aesthet Surg J. 2016;36:1176–87.

    Article  PubMed  Google Scholar 

  17. Wu YC, Wang YC, Wang WT, Wang HD, Lin HH, Su LJ, et al. Fluorescent nanodiamonds enable long-term detection of human adipose-derived stem/stromal cells in an in vivo chondrogenesis model using decellularized extracellular matrices and fibrin glue polymer. Polymers (Basel). 2019;11:1391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Calvert JW, Brenner K, DaCosta-Iyer M, Evans GR, Daniel RK. Histological analysis of human diced cartilage grafts. Plast Reconstr Surg. 2006;118:230–6.

    Article  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  CAS  PubMed  Google Scholar 

  21. Wang G, An Y, Zhang X, Ding P, Bi H, Zhao Z. Chondrocyte spheroids laden in GelMA/HAMA hybrid hydrogel for tissue-engineered cartilage with enhanced proliferation, better phenotype maintenance, and natural morphological structure. Gels. 2021;7:247.

    Article  CAS  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Mende W, Götzl R, Kubo Y, Pufe T, Ruhl T, Beier JP. The role of adipose stem cells in bone regeneration and bone tissue engineering. Cells. 2021;10:975.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shafaei H, Kalarestaghi H. Adipose-derived stem cells: an appropriate selection for osteogenic differentiation. J Cell Physiol. 2020;235:8371–86.

    Article  CAS  PubMed  Google Scholar 

  25. Mangiavini L, Peretti GM, Canciani B, Maffulli N. Epidermal growth factor signalling pathway in endochondral ossification: an evidence-based narrative review. Ann Med. 2022;54:37–50.

    Article  CAS  PubMed  Google Scholar 

  26. Schott NG, Friend NE, Stegemann JP. Coupling osteogenesis and vasculogenesis in engineered orthopedic tissues. Tissue Eng Part B Rev. 2021;27:199–214.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ozturk SK, Habesoglu TE, Ihvan A, Palaoglu I, Cokay BI, Habesoglu MO. Effects of esterified hyaluronic acid, adipose tissue, and blood glue on survival of diced cartilage grafts. J Craniofac Surg. 2022;33:1614–8.

    Article  PubMed  Google Scholar 

  28. Habanjar O, Diab-Assaf M, Caldefie-Chezet F, Delort L. 3D cell culture systems: tumor application, advantages, and disadvantages. Int J Mol Sci. 2021;22:12200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim W, Gwon Y, Park S, Kim H, Kim J. Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration. Bioact Mater. 2022;19:50–74.

    Article  CAS  PubMed  Google Scholar 

  30. Dsouza VL, Kuthethur R, Kabekkodu SP, Chakrabarty S. Organ-on-chip platforms to study tumor evolution and chemosensitivity. Biochim Biophys Acta Rev Cancer. 2022;1877:188717.

    Article  CAS  PubMed  Google Scholar 

  31. Lee NH, Bayaraa O, Zechu Z, Kim HS. Biomaterials-assisted spheroid engineering for regenerative therapy. BMB Rep. 2021;54:356–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kronemberger GS, Matsui RAM, Miranda GASCE, Granjeiro M, Baptista LS. Cartilage and bone tissue engineering using adipose stromal/stem cells spheroids as building blocks. World J Stem Cells. 2020;12:110–22.

    Article  PubMed  PubMed Central  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. Nakamura A, Murata D, Fujimoto R, Tamaki S, Nagata S, Ikeya M, et al. Bio-3D printing iPSC-derived human chondrocytes for articular cartilage regeneration. Biofabrication. 2021;13:044103.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This article was funded by China Postdoctoral Science Foundation with the number of 2020M670001ZX, and by Peking University Health Science Center Youth Innovation Cultivation Foundation.

Author information

Author notes

  1. Guanhuier Wang and Mengying Jin have contributed equally and were co-first authors.

  2. Yang An and Zhenmin Zhao have contributed equally and were co-corresponding authors.

Authors and Affiliations

  1. Department of Plastic Surgery, Peking University Third Hospital, No. 49 of North Huayuan Road, Haidian District, Beijing, 100191, China

    Guanhuier Wang, Mengying Jin, Yimou Sun, Yang An & Zhenmin Zhao

Authors
  1. Guanhuier Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mengying Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yimou Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang An
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhenmin Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yang An or Zhenmin Zhao.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical statement

This animal study was approved by the Institutional Animal Care and Use Committee of ‘Peking University Health Science Center’, and all procedures were strictly performed following the guidance of care and use of laboratory animals (IACUC no. LA2021375).

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, G., Jin, M., Sun, Y. et al. Combining Diced Cartilage with Chondrocyte Spheroids in GelMA Hydrogel: An Animal Study in Diced Cartilage Grafting Technique. Tissue Eng Regen Med 20, 285–294 (2023). https://doi.org/10.1007/s13770-022-00499-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13770-022-00499-5

Keywords

Search

Navigation