Page 21 - IJB-10-3

International Journal of Bioprinting Supramolecular hydrogels as bioinks

Dai et al. introduced a novel dynamic gel for hydrogels have been used as favorable materials for
69
bioprinting cell-filled structures for osteochondral tissue engineering. 87
regeneration (Figure 4C). The bioink, which is made In summation, the specialized cone-like molecular
up of acrylate β-CD, Dopa-functionalized GelMA, shape of CD enables chemical modifications of the molecule
and GelMA, creates a dynamic network through host– to improve inherent features such as cellular adhesion,
guest interactions. This network amplifies mechanical differentiation, self-healing, and biodegradability. Among
characteristics, increases cell adhesion, encourages the structural variations of CD, polyrotaxane-based
adaptability, and permits variable modulus. To generate supramolecular hydrogels have the highest efficiency, in
a heterogeneous construct that mimics the osteochondral terms of tissue engineering aspects. Furthermore, the wide
environment, chondrogenic and osteogenic components range of available guest molecules for CD-crosslinked
are incorporated in diverse zones through the sustained supramolecular hydrogel formation offers a vast selection of
drug release from β-CD cavities. The bioink exhibits versatile hydrogels suitable for both injectable applications
encouraging in vivo and in vitro regeneration outcomes, and 3D bioprinting.
pointing to its potential for broad application in 3D
bioprinting for tissue engineering. 5.2.1. Pseudorotaxane-based
69
Similarly, a different injectable and 3D-printed bi- supramolecular hydrogels
layered osteochondral hydrogel, consisting of β-tricalcium Cyclodextrins (CDs) can create supramolecular assemblies
phosphate (TCP), methacrylated sodium alginate, through interlinking within main chain polymer segments
and methacryloyl gelatin with a compositional gradient, or forming side chain complexes via physical interactions or
was reported recently. The hydrogel comprised an osseous covalent bonds. If these structures are capable of reversible
layer (OLH) with a biochemical gradient of kartogenin movement along the macromolecular backbone or lateral
(KGN) and a chondral layer (CLH) (Figure 4D). chains, they are referred to as PpRXs. Conversely, if the
Experiments performed both in vitro and in vivo revealed mobility of CD is limited because of the presence of bulky
that at high KGN concentrations, bone MSCs (BMSCs) molecules (referred to as stopper molecules) entrapped
promote chondrogenesis, while low KGN concentrations at the ends of PpRXs, these assemblies are termed
72
when combined with β-TCP synergistically enhance polyrotaxanes. Polyrotaxanes involve the threading of
osteogenic growth via endochondral ossification. Different CDs onto the polymer chain, achieved either through
concentrations of KGN within the hydrogel formulations the conventional 1:1 covalent bonding between stopper
impacted their mechanical strength and swelling behavior. molecules or by incorporating extra linker molecules or
The sustained release of KGN varied accordingly, with intermolecular hydrophilic interactions. The crosslinking
OLH/β-TCP(+)/KGN(+) releasing the highest amount of density can be increased by utilizing a dual-threaded
88
KGN. The combination of β-TCP and KGN synergistically redox-responsive inclusion complex in a 1:2 ratio. From
promoted osteogenic differentiation through endochondral a tissue engineering perspective, polyrotaxane-based
ossification in OLH, while a low concentration of KGN supramolecular hydrogels possess distinct advantages,
effectively regulated the chondrogenic differentiation of notably improved degradability, substantial stretchability,
BMSCs. Evaluation in a rat knee joint trochlear defect self-repair capabilities, and inherent supramolecular
model reported that the chondrogenic kartogenin (C-K) mobility. Furthermore, copolymers incorporating
and osteogenic tissue kartogenin (O-TK) group exhibited polyrotaxanes have demonstrated enhanced cellular
the most complete defect filling, highest International adhesion and augmented differentiation, signifying
Cartilage Repair Society (ICRS) score, and superior their potential to promote tissue development and
89,90
osteochondral tissue regeneration, supported by micro- regeneration. The hydrogel formed through chemical
computed tomography (microCT or μCT) and histological modifications of CD on the polyrotaxane, such as
analysis. Immunohistochemical staining and Raman introducing aldehyde groups, facilitates instant gelation,
spectroscopy indicated an excellent microenvironment suggesting efficient self-healing and biodegradability as
91
for osteochondral repair due to the synergy between evidenced by studies involving cell encapsulation.
KGN and β-TCP in the osseous layer. Further studies are Cyclodextrins (CDs) are cyclic oligosaccharides capable
warranted to elucidate the precise molecular mechanism of forming supramolecular inclusion complexes (SICs)
and optimize KGN ratios for clinical translation. In by binding to hydrophobic guest molecules, as noted by
70
another study, functional α-CD nanobeads threaded onto Uekama et al. Notably, CDs can also produce PpRXs, an
92
PEG chains enable the creation of modular PEG hydrogels SIC, when interacting with linear synthetic polymers, like
with controllable properties for stem cell culture and PPG or PEG. A PpRX-based supramolecular hydrogel
92
differentiation. CD-based host–guest supramolecular system can function as a depot for sustained drug or

Volume 10 Issue 3 (2024) 13 doi: 10.36922/ijb.3223