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International Journal of Bioprinting Cellulose-based bio-inks for bone and cartilage TE

Figure 4. (A) Multi-layered osteochondral tissue defects require zone-specific hierarchical repair strategies. (B) Multi-channel 3D plotting allows the fabri-
cation of artificial full-thickness osteochondral plugs . Image reproduced with permission. (C) 3D multichannel plotting of the scaphoid bone consisting
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of CPC with mc10 as support ink . Image reproduced with permission. (D) Full and section view of the designed CAD model. The channel branches
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from one into four channels . (E) The plotted scaffold was manually perfused with undiluted phenol red solution; after perfusion, only the hydrogel was
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stained, evidencing perfusion through the plotted channel structure . Image reproduced with permission.
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Precise temporal and spatial representation of signaling TE because of its easy chemical modification, good
molecules, such as gene complexes, is a considerable viscosity, shear-thinning, and pH-responsiveness . These
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challenge for many researchers. Researchers have sought characteristics primarily depend on the cellulose source
to prepare a gene-activated bio-ink that can be combined and CMC production method . The transition between
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with 3D bioprinting to engineer tissue scaffolds that can sol and gel that occurs with pH changes makes them special
spatially and temporally control gene expression within pH-responsive hydrogels. CMC has excellent structural and
the tissues. Gonzalez-Fernandez et al. mixed MC with mechanical stability at pH 3–10 . When the pH is greater
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Alg to obtain pore-forming bio-inks loaded with bone than 10, the hydrogen bonds between CMC molecules are
marrow MSCs . Using MC as a sacrificial ink, the scaffold broken, resulting in a sharp decrease in the viscosity of the
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could progressively form pores and release chondrogenic CMC and loss of mechanical stability; conversely, when
molecules (combination of TGF-β3, BMP2, and SOX9) pH is less than 3, CMC forms precipitates .
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within a controlled range to facilitate early transfection of CMC is mainly prepared via the Williamson-ether
the encapsulated MSCs in vivo and in vitro. The addition of reaction in two steps: alkylation and etherification. CMC
MC also improved the printability of the ink and the high can also be formed by generating cellulose triacetate (CTA)
fidelity of the scaffold. However, the sacrifice of MC also intermediates in a mildly acidic medium, followed by in
disrupts the mechanical properties of the scaffold, which situ esterification reactions .
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may be challenging when grafting into bone defects that
are subject to high stress. 3.2.2. CMC 3D bioprinting in cartilage and bone repair
Since the carboxyl group in CMC can act as a nucleation
3.2. Carboxymethyl cellulose site for calcium ions and improve the biomineralization
3.2.1. Physicochemical properties and process, CMC is often combined with other substances to
preparation of carboxymethyl cellulose prepare bone scaffolds . CMC, as a negatively charged
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Carboxymethyl cellulose (CMC) is a water-soluble substance, also plays an important role in TE. Chen et al.
cellulose derivative obtained via chemical modification. printed a composite scaffold composed of hydroxyapatite
This modification is performed by replacing the hydroxyl and polymers (gelatin, CS, and CMC) . Positively charged
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group on the glucopyranose chains of cellulose with CS and negatively charged CMC can establish powerful
carboxymethyl groups (–CH2COOH) . It has a wider electrical interactions to enhance the mechanical properties
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range of use than MCs, such as drug administration, of the scaffold. The hybrid membrane composed of CS,
biomedical regeneration, textiles, paper, wastewater CMC, and hydroxyapatite exhibited good cell viability
treatment, and food products. CMC is considered a and osteocalcin expression and promoted the infiltration
promising scaffold biomaterial for 3D bioprinting in of bone tissue in vivo . Janarthanan et al. added Schiff’s
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Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023)
V 221 https://doi.org/10.18063/ijb.v9i1.637