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International Journal of Bioprinting DNA-functionalized hyaluronic acid bioink

bonds between DNA crosslinkers are reversible, this precise structural customization and the ability to fine-
hydrogel has good self-healing properties, which allows tune their physical and chemical properties. Recently,
the hydrogel to be printed and reshaped without damaging a review unveils the unprecedented prospects of DNA
cells. The authors successfully cultured human-induced integration into dynamic supramolecular hydrogels in
pluripotent stem cells using DyNAtrix and observed cartilage tissue engineering and illuminates the strategy
their proliferation, morphogenesis, and differentiation of incorporating reconfigurable DNA building blocks into
in the hydrogel, which holds great potential in tissue hyaluronic acid hydrogels, which serve as crosslinking
engineering (Figure 8e and f). nodes within network structures, with implications for
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Taken together, the integration of DNA hybrid advancing cartilage repair through the rational design of
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hydrogels into cartilage engineering holds immense responsive smart hydrogels.
promise for driving the field forward. These hydrogels The complex interplay between in vivo cell interactions
offer precise control over cellular behaviors through and the ECM relies on the temporal dynamics and
customizable structures. This modulation capacity enables spatial definition of physical and chemical cues. This
diverse applications, from shielding encapsulated cells from interaction replicates stem cell microenvironments and
shear forces to enabling controlled cell release. Beyond cell guides suitable cell phenotypes. Unlike conventional
encapsulation, DNA hybrid hydrogels function as versatile static hydrogels, dynamic DNA–HA hybrid hydrogels not
carriers delivering therapeutics, such as drugs, cytokines, only fulfill the biological and mechanical requirements of
and exosomes, to targeted sites in order to boost treatment bioinks, but also exhibit in situ responsiveness to cellular
effectiveness. However, several limitations surrounding the signals and external stimuli. This attribute holds promise
application of DNA-functionalized hydrogels in cartilage for simulating the physicochemical characteristics of
regeneration should be acknowledged: (i) impurities or chondrocyte ECMs. Despite these advantages, several
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non-specific hybridization, which leads to reduced stability challenges remain in advancing the utilization of DNA–
and responsiveness of hydrogels; (ii) interference by HA hybrid hydrogels for cartilage tissue regeneration.
enzyme residues or inhibitors, which makes the preparation Variations in synthesis methodologies yield DNA hydrogels
process of hydrogels complex and uncontrollable; and with distinct pharmacokinetics, suggesting varying
(iii) rejection by the immune system or adverse reaction anti-enzyme activities. Distinct stimuli should induce
stemming from exogenous gene expression, which lowers different kinetic behaviors in DNA hydrogels. However,
biocompatibility and safeness of hydrogels. Nevertheless, by comprehensive studies on the pharmacokinetics of DNA
mimicking synthetic ECMs using specific aptamers, DNA- hydrogels are currently limited, possibly due to research
functionalized hydrogels facilitate cell-specific recruitment limitations or insufficient focus on this area. In-depth
and differentiation, which are the core functions required kinetic inquiries will contribute to the informed design
by tissue engineering strategies. With their multifaceted of DNA hydrogels for specific applications, fostering
capabilities, DNA hybrid hydrogels emerge as a dynamic the development of controlled release hydrogels and
toolset with transformative potential, poised to redefine tissue engineering advancements. With the continuous
cartilage engineering and tissue regeneration. development of DNA nanotechnology, the structure and
function of DNA-functionalized hydrogels will become
5. Conclusion more diverse and sophisticated to align with different
Hyaluronic acid is a prominent polysaccharide found biomedical needs. For example, increasing studies
in living tissues, possessing high potential for hydrogel focus on exploring various DNA crosslinking strategies,
fabrication due to its exceptional biocompatibility. optimizing the mechanical properties of DNA hydrogels,
Nevertheless, conventional crosslinking methods for HA, and achieving dynamic regulation of mechanical signals.
which often involve the use of chemical agents or the Moreover, improving enzyme resistance and immune
introduction of functional groups, limit the dynamic and evasion abilities of DNA hydrogels, as well as controlling
adaptable characteristics of the resulting products. This their degradation rate and products, are also important
renders them less than optimal for cartilage applications. directions. Furthermore, by integrating different
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Conversely, DNA, as a biological macromolecule, functional elements, such as nucleic acid aptamers,
exhibits enhanced biocompatibility and degradability. nucleases, gene carriers, and nanoparticles, more DNA-
It offers exceptional structural programmability and functionalized hydrogels can be developed as bioinks to
multifunctionality, allowing for the customization of construct organoids with complex structure and function.
desired attributes, such as specific recognition, targeted In summary, the convergence of DNA and HA presents
specificity, and biocatalytic activity. The inherent an intriguing bioink platform, which has the potential to
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flexibility of DNA molecules empowers hydrogels with be widely applied in the field of cartilage repair.

Volume 10 Issue 2 (2024) 39 doi: 10.36922/ijb.1814