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International
Journal of Bioprinting
REVIEW ARTICLE
DNA-functionalized hyaluronic acid bioink in
cartilage engineering: a perspective
Mengmeng Li 1,2† , Yan Wu 1,2† , Miaomiao Wang 1,2† , Wencai Zhang *, Peiran Song *,
1,2
3
and Jiacan Su 1,2,4 *
1 Organoid Research Center, Institute of Translational Medicine, Shanghai University, Shanghai,
China
2 National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University,
Shanghai, China
3
Department of Orthopedics, First Affiliated Hospital, Jinan University, Guangzhou, China
4 Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of
Medicine, Shanghai, China
(This article belongs to the Special Issue: Application of 3D Bioprinting Materials: Hyaluronic Acid-Based Bioink)
Abstract
Degenerative osteoarthritis, a common sequela of articular cartilage defect, significantly
impacts the quality of life of millions of individuals worldwide. Three-dimensional (3D)
bioprinting has emerged as an advanced tissue engineering strategy, offering precise
† These authors contributed equally spatial arrangements of cells, hydrogels, and bioactive cues. Hyaluronic acid (HA) is a
to this work. crucial component of bioink designed for fabricating cartilage tissue. However, creating
*Corresponding authors: a bioink that closely mimics the cartilaginous extracellular matrix (ECM) still remains a
Wencai Zhang challenge. HA hydrogels have limitations in recapitulating tunable mechanical properties,
(wczhang@jnu.edu.cn) stimuli responsiveness, and flexibility in ligands’ adhesion akin to those of native tissues.
Peiran Song In recent years, DNA has emerged as a smart biomaterial that endows hydrogels with
(songpeiran@163.com) tunable properties and allows for precise structural customization of the hydrogels due
Jiacan Su to its unique programmability. Integrating reversible DNA linkages, reconfigurable DNA
(drsujiacan@163.com)
architectures, DNA plasmid, and targeted DNA aptamers into HA hydrogels allows them
Citation: Li M, Wu Y, Wang M, to respond to the extracellular environment and express desired molecules, making
Zhang W, Song P, Su J. DNA-
functionalized hyaluronic acid them ideal artificial ECMs for 3D bioprinting of cartilage tissue. This review targets this
bioink in cartilage engineering: challenge by highlighting the characteristics of DNA moieties designed as reversible
a perspective. Int J Bioprint. crosslinkers, responsive units, and adhesion ligands to functionalize HA hydrogels.
2024;10(2):1814.
doi: 10.36922/ijb.1814 Furthermore, we offer perspectives on how DNA-functionalized HA hydrogels can be
harnessed to create dynamic and biomimetic bioink capable of recapitulating the more
Received: August 24, 2023
Accepted: November 21, 2023 complex functions required for cartilage tissue engineering.
Published Online: January 16, 2024
Copyright: © 2024 Author(s). Keywords: Hyaluronic acid; DNA functionalization; Cartilage regeneration;
This is an Open Access article Tissue engineering
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited. 1. Introduction
Publisher’s Note: AccScience Articular cartilage, a load-bearing connective tissue located at the bone interfaces, facilitates
Publishing remains neutral with smooth and frictionless skeletal movements. However, cartilage defects due to traumatic
regard to jurisdictional claims in
published maps and institutional injury or disease can lead to its degradation, resulting in widespread cartilage loss and
1-3
affiliations. potentially causing degenerative osteoarthritis. Adopting different tissue engineering
Volume 10 Issue 2 (2024) 26 doi: 10.36922/ijb.1814

