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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
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