Page 221 - IJB-9-5

International Journal of Bioprinting Hydrogels for 3D bioprinting

and the optimal crosslinking temperature of the gelatin while achieving high hepatocyte activity. Khati et al.
[66]
scaffold is 20°C after printing. Chemically crosslinking blended decellularized liver matrix (dLM) with gelatin
gelatin hydrogels is a simple method. In vitro cytotoxicity and PEG for 3D bioprinting. The addition of gelatin and
experiments using 3T3-L1 pre-adipocytes showed that the PEG improved the rheology, printability, and mechanical
bioprinted scaffolds will not produce indirect cytotoxicity stability of the bioink, and the 3D-printed structure and
to cells. Finally, they also tested that the scaffold can dLM-rich growth factors supported the growth of HepG2
promote the adhesion, proliferation, and adipogenic cells and improved the cytocompatibility of the hydrogel.
differentiation of human primary pre-adipocytes . The highly crosslinked dLM-G-PEG laid the foundation
[56]
for subsequent toxicological studies on HepG2 cells.
3.1.3. Silk fibroin
Silk fibrin (SF) is a natural fiber polymer extracted 3.1.5. Collagen
from silk. It not only has the characteristics of a natural As one of the major components of dECM, collagen is the
hydrogel material but also has high tensile strength, most widely distributed protein in the body. Its presence in
excellent biological properties, and low inflammation. all connective tissues makes it the most studied biomolecule
Because of the above characteristics, it has a wide range of in the ECM . Collagen is widely studied and applied in
[67]
applications in skin regeneration and wound healing [59,60] . tissue engineering and regenerative medicine because of its
SF is modified by grafting, coupling reaction, and amino biodegradability, biocompatibility, low immunogenicity,
acid modification compared with fibrin, hyaluronic acid, and easy availability. However, after applying them to 3D
and collagen . Silk fibroin-gelatin (SF-Gel) hydrogel bioprinting, researchers found that, similar to dECM,
[61]
bioink is one of the most commonly used combinations. collagen often exhibits poor mechanical properties and
This is because of their inherent biocompatibility, structural stability , so exogenous crosslinking methods
[68]
bioactive signatures, binding affinity for cells, and tunable have been introduced to increase the crosslink density
mechanical properties. Castilho et al. fabricated a new to improve its mechanical properties and printability.
[62]
type of photocrosslinkable bioinks based on proteinaceous Chemical methods often include the introduction of
polymers, namely gelatin and silk fibroin, and allowed chemical crosslinking agents such as aldehydes ,
[69]
the 3D writing of microscale, cell-laden fibers through a genipin , and carbodiimide to enhance the mechanical
[71]
[70]
cell electro-writing process (CEW). They were found to properties of collagen. Physical methods such as UV
have good mechanical properties, reduced cell-filled fiber irradiation and dehydrogenation heat can eliminate
[72]
size (5–40 μm), and wonderful resolution and patterning the negative effects of using chemical crosslinking agents.
accuracy compared to conventional extrusion bioprinting. Serna et al. introduced a photo-reactive agent, riboflavin,
[73]
These significant features of the new photosensitive which was used in conjunction with UV irradiation to
hydrogel bioinks and CEW processes will allow the creation enhance the mechanical properties of collagen. However,
of micro-structured scaffolds that can better mimic the physical methods inevitably cause conformational
cellular microenvironment of regenerative medicine (RM) changes in the polypeptide chains as well as collagen
(e.g., muscle fibers, tendons, and neural networks) and denaturation . In addition to the above-mentioned
[74]
organ-on-a-chip models. exogenous crosslinking methods, combining collagen with
some polymeric materials (e.g., sodium alginate) can also
3.1.4. Decellularized extracellular matrix improve its mechanical properties and printability. Clark
While a variety of hydrogels are already being used by et al. modified collagen and mixed it with different
[75]
many researchers today to configure bioinks for 3D concentrations of thiolated HA 3:1 and loaded HepG2
bioprinting, decellularized extracellular matrix (dECM)- and patient-derived glioblastoma multiforme (GBM) cells.
based bioinks with tissue specificity are gaining popularity. The concentration of HA was finally optimized to 15 mg/
The dECM of chemically- and physically-removed cells mL to match the bioprinting, and the printed organoid
resembles the ECM of target tissues in terms of chemical had excellent mechanical properties and could be used in
composition and structural complexity in an idiosyncratic subsequent drug screening applications.
environment . However, it is difficult to use dECM
[63]
alone as a bioprinting ink due to its poor mechanical In summary, most of the above-mentioned natural
stability . Therefore, dissolved dECM is often mixed polymer-based hydrogels as bioinks for 3D bioprinting
[64]
with other polymers or printed with other structural have good biocompatibility, low immunogenicity, and low
support materials. Zhuang et al. mixed dECM and inflammation as well as suitable biodegradability, and these
[65]
modified gelatin with nanoclay to make a new bioink. advantages make them widely used in tissue engineering
The concentration of dECM was as high as 75%, and the and regenerative medicine. However, as they mostly exhibit
composite bioink maintained good printing performance weak mechanical properties and poor structural stability, it

Volume 9 Issue 5 (2023) 213 https://doi.org/10.18063/ijb.759