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RESEARCH ARTICLE

3D Bioprinting of Biomimetic Bilayered Scaffold

Consisting of Decellularized Extracellular Matrix and

Silk Fibroin for Osteochondral Repair

Xiao Zhang , Yang Liu , Qiang Zuo , Qingyun Wang, Zuxi Li, Kai Yan, Tao Yuan, Yi Zhang,
†
†
†
Kai Shen, Rui Xie, Weimin Fan*
Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
† These authors contributed equally to this work

Abstract: Recently, three-dimensional (3D) bioprinting technology is becoming an appealing approach for osteochondral
repair. However, it is challenging to develop a bilayered scaffold with anisotropic structural properties to mimic a native
osteochondral tissue. Herein, we developed a bioink consisting of decellularized extracellular matrix and silk fibroin to
print the bilayered scaffold. The bilayered scaffold mimics the natural osteochondral tissue by controlling the composition,
mechanical properties, and growth factor release in each layer of the scaffold. The in vitro results show that each layer of
scaffolds had a suitable mechanical strength and degradation rate. Furthermore, the scaffolds encapsulating transforming
growth factor-beta (TGF-β) and bone morphogenetic protein-2 (BMP-2) can act as a controlled release system and promote
directed differentiation of bone marrow-derived mesenchymal stem cells. Furthermore, the in vivo experiments suggested that
the scaffolds loaded with growth factors promoted osteochondral regeneration in the rabbit knee joint model. Consequently,
the biomimetic bilayered scaffold loaded with TGF-β and BMP-2 would be a promising strategy for osteochondral repair.
Keywords: Tissue engineering; Three-dimensional bioprinting; Osteochondral repair; Extracellular matrix; Silk fibroin;
Polycaprolactone

*Correspondence to: Weimin Fan, Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029,
China; fanweimin1959@vip.sina.com
Received: July 8, 2021; Accepted: August 20, 2021; Published Online: September 14, 2021
Citation: Zhang X, Liu Y, Zuo Q, et al., 2021, 3D Bioprinting of Biomimetic Bilayered Scaffold Consisting of Decellularized Extracellular
Matrix and Silk Fibroin for Osteochondral Repair. Int J Bioprint, 7(4):401. http://doi.org/10.18063/ijb.v7i4.401

1. Introduction regeneration research [9,10] . Ideal bilayered scaffolds should
be equipped with biological and physical properties that
Osteochondral defects, which occur due to inflammation, can match the native tissues [11,12] . However, traditional
trauma or aging, involve lesions of cartilage and tissue engineering strategies have not been able to develop
subchondral bone and constitute a significant healthcare a bilayered scaffold with anisotropic structural properties
burden [1,2] . Current treatment strategies include to mimic a native osteochondral tissue . Furthermore,
[13]
microfracture, autologous chondrocyte implantation, each layer of the current bilayered scaffolds is usually
and mosaicplasty. Nonetheless, there are still failures fabricated separately and then joined together, resulting
and undesirable complications in the above-mentioned in a poor integration between two layers of the bilayered
treatment strategies [3-6] . In recent years, tissue engineering construction [11,14,15] . Recently, 3D bioprinting has
that provides suitable biomaterials to support the growth emerged as a continuous way to fabricate biomimetic and
and differentiation of cells provides a promising strategy complex tissue structure, such as osteochondral bilayered
for osteochondral regeneration [7,8] . The application of structure [11,13,16] . Three-dimensional (3D) bioprinting
bilayered scaffolds that concerned physical structure of technology integrates equipment manufacturing industry,
osteochondral tissue has been the focus of osteochondral biomaterial science, and computer aided to fabricate

© 2021 Zhang, et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
reproduction in any medium, provided the original work is cited.
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