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International Journal of Bioprinting Supramolecular hydrogels as bioinks

inherently influences the injectability of the hydrogel. In vivo. They can be formed by the self-assembly of naturally
the case of non-covalent interactions, hydrophobic lipid occurring amphiphiles that contain biomolecules. Likewise,
dodecyl chains (C12) were modified with hydroxypropyl water-mediated multivalent crosslinking of biodegradable
methylcellulose (HPMC) via isocyanate coupling and biocompatible synthetic polymers can be formed with
chemistry. This modification, along with Arg-Gly-Asp host and guest functionalities. Additionally, biostability
7,8
(RGD)-attached 30 nm poly(ethylene glycol) (PEG)- is essential for supramolecular hydrogels in the detection
polylactic acid (PLA) NPs, resulted in a synthetic, scalable, and management of cancer. Strategies, such as designing
28
and biodegradable hydrogel suitable for cell delivery. hydrogelators based on nucleobase–peptide bioconjugates
3+
Typically, cells are co-injected with hydrogels to prevent cell or utilizing dopamine (Dopa)-Fe complexation, have
death and enhance cell availability in the tissue area. In this been employed to enhance the biostability of these
context, supramolecular hydrogels prove highly beneficial hydrogels, offering resistance to proteases and oxidative
for making self-healing hydrogels. 29,30 The supramolecular degradation. 7,8,38 Furthermore, bioactive molecules (e.g.,
assembly also promotes the injectability of the hydrogel growth factors and cytokines) can be incorporated into
and can be used for sustained drug release applications. supramolecular hydrogel bioinks to elevate cellular
A notable example is presented by Mol et al., wherein responses and encourage tissue regeneration. The hydrogel
a PEG hydrogel, incorporating ureido-pyrimidinone network can immobilize these bioactive molecules,
(UPy) units, demonstrated the controlled release of leading to a sustained release over time, augmenting their
extracellular vesicles for 4 days post-injection. Recently, efficacy, and diminishing the necessary dosage. Moreover,
31
the formulation of tunable supramolecular polymer-NP supramolecular hydrogel bioinks can be loaded with cells
hydrogels has been developed. The network polymer, or other biological agents, such as drugs or NPs, for precise
hydrophobically modified cellulose, dynamically interacts and localized administration. 5,7,8
through multivalent connections and self-assembles with
non-covalent core–shell NPs as a crosslinker. 32 4. Supramolecular hydrogels for
3D bioprinting applications
3.3. Biological properties
The exceptional biocompatibility, injectability, and 3D bioprinting is a technique where live cells, encapsulated
adjustable physical and mechanical characteristics of in hydrogel materials, are employed to construct 3D
39
supramolecular hydrogels have led to their increased structures that mimic native tissues. The emerging
interest in tissue engineering, especially 3D bioprinting 3D bioprinting technique enables the fabrication of
applications. One of the most important advantages personalized tissue engineering scaffolds for precise therapy.
7,8
of supramolecular hydrogels in tissue engineering is Successful application relies on advanced bioinks meeting
their ability to mimic the extracellular matrix (ECM) criteria, like extrudability, rapid gelation, layer adhesion,
of native tissues. The ECM provides structural and self-healing capability, biocompatibility, biodegradability,
biochemical support to cells, and its mechanical and stability in physiological conditions. To enhance the
characteristics and composition greatly affect cell behavior, properties of current bioinks, the incorporation of diverse
40
including migration, differentiation, and proliferation. chemical strategies is essential.
Supramolecular hydrogels can be tailored to simulate the Most of these supramolecular hydrogels are favorable
ECM of diverse tissues by integrating specific amino acid candidates for tissue engineering and 3D bioprinting
sequences, such as RGD or Tyr-Ile-Gly-Ser-Arg (YIGSR), applications. The hydrogels were found to be cytocompatible,
that encourage cell adhesion and migration. 33,34 Further, and the cell viability values range between 74 and 100%. 41-43
some supramolecular hydrogels self-assemble to create 3D-printed PNAGA20%-Clay composite scaffold, reported
a 3D network of nanofibrous structures that mimics the by Zhai et al., facilitated the differentiation of primary rat
ECM of cells. 35-37 osteoblasts (ROBs) into osteogenic cells following in vivo
2+
To prevent harmful accumulation in the human implantation with sustained release of intrinsic Mg and
4+
body, biomaterials must exhibit both biodegradability Si . p(N-acryloyl glycinamide) (PNAGA) and poly(N-
and biocompatibility. Supramolecular hydrogels, unlike acryloyl glycinamide-co-carboxybetaine acrylamide)
covalent hydrogels, possess non-covalent crosslinkages (PNAGA-PCBAA) hydrogels also exhibit antifouling
−2
that allow for spontaneous degradation or metabolism ability with very low (≈ 0.45 μg cm ) protein adsorption
42
in physiological environments. These hydrogels are due to the introduction of PCBAA.
promising as biomaterials for regenerating cell matrices Interestingly, supramolecular hydrogels formed based
and drug delivery vehicles as they demonstrate good on the sliding filament theory of muscle contraction
biodegradability and biocompatibility both in vitro and in proved superior to the hydrogen-bond-based physically

Volume 10 Issue 3 (2024) 6 doi: 10.36922/ijb.3223