Bioprinting of a zonal‐specific cell density scaffold: A biomimetic approach for cartilage tissue engineering

A. Dimaraki, P. J. Díaz‐payno, M. Minneboo, M. Nouri‐goushki, M. Hosseini, N. Kops, R. Narcisi, M. J. Mirzaali, G. J.V.M. van Osch, L. E. Fratila‐apachitei, A. A. Zadpoor*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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The treatment of articular cartilage defects remains a significant clinical challenge. This is partially due to current tissue engineering strategies failing to recapitulate native organization. Articular cartilage is a graded tissue with three layers exhibiting different cell densities: the superficial zone having the highest density and the deep zone having the lowest density. However, the introduction of cell gradients for cartilage tissue engineering, which could promote a more biomimetic environment, has not been widely explored. Here, we aimed to bioprint a scaffold with different zonal cell densities to mimic the organization of articular cartilage. The scaffold was bioprinted using an alginate‐based bioink containing human articular chondrocytes. The scaffold design included three cell densities, one per zone: 20 × 106 (superficial), 10 × 106 (middle), and 5 × 106 (deep) cells/mL. The scaffold was cultured in a chondrogenic medium for 25 days and analyzed by live/dead assay and histology. The live/dead analysis showed the ability to generate a zonal cell density with high viability. Histological analysis revealed a smooth transition between the zones in terms of cell distribution and a higher sulphated glycosaminoglycan deposition in the highest cell density zone. These findings pave the way toward bioprinting complex zonal cartilage scaffolds as single units, thereby advancing the translation of cartilage tissue engineering into clinical practice.

Original languageEnglish
Article number7821
JournalApplied Sciences (Switzerland)
Issue number17
Publication statusPublished - 25 Aug 2021

Bibliographical note

Funding Information:
Funding: This research was funded by the Dutch Medical Delta project: RegMed4D.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (


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