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International Journal of Bioprinting DNA-functionalized hyaluronic acid bioink
2.1.1. Assembly guided by DNA sticky ends and enzymatic responsiveness can be hybridized via sticky
Sticky ends of a DNA molecule refer to the protruding parts ends that affix to two types of building blocks, such as
of one strand beyond its complementary strand within the linear double-stranded DNA and Y-shaped DNA. This
double helix. This structural characteristic allows the DNA adaptability of dynamic properties was achieved through
chains to engage in hybridization, leveraging the principle precise modulation of the ratio of these constituent building
of base pair complementarity. Based on this concept, a blocks (Figure 2b). This method relies on hybridization
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highly entangled 3D DNA hydrogel was fabricated through reactions between single-stranded DNA molecules with
the self-assembly of short linear double-stranded DNA complementary sequences to create a 3D network structure.
(dsDNA) units, each equipped with sticky ends (Figure 2a). The core advantages of this method lie in its simplicity,
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DNA hydrogels can also be fabricated via branched DNA speed, and controllability, which allow for adjustments in
gelation systems. The assembly of Y-shaped DNA units was hydrogel porosity and stiffness through an alteration to
accomplished by means of i-motif DNA structures forming the length, type, and concentration of DNA molecules.
at the sticky ends. As a consequence, the fabricated DNA However, a drawback of this method is its reduced stability
hydrogels exhibited prompt responsiveness to alterations in and responsiveness, marked by its susceptibility to factors
environmental pH, enabling controlled encapsulation and such as nucleases and temperature fluctuations, which
release cargos. DNA hydrogels with properties of thermal could lead to hydrogel disassembly or annealing.
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Figure 2. Assembly strategies of DNA hydrogels. (a) A pure DNA hydrogel formed by direct assembly of dsDNA monomers with sticky ends. Reprinted
with permission from ref. Copyright © 2014 Wiley. (b) Direct assembly of sticky ends of Y-scaffold and linkers for pure DNA hydrogel. Reprinted with
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permission from ref. Copyright © 2011 Wiley. (c) DNA hydrogels by crosslinking and subsequent PCR primer extension. Reprinted with permission
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from ref. Copyright © 2013 Wiley. (d) DNA initiator-triggered clamped hybridization chain reaction self-assembly process. Reprinted with permission
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from ref. Copyright © 2017 Wiley. (e) Surface-initiated DNA hydrogel formation. Reprinted with permission from ref. Copyright © 2017 Wiley.
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Volume 10 Issue 2 (2024) 29 doi: 10.36922/ijb.1814

