Page 18 - IJB-9-2

International Journal of Bioprinting Extrusion-based biomaterial inks

differentiation. Hyaluronic acid, a linear glycosaminoglycan enzyme-crosslinked gelatin/hydroxyapatite scaffolds
composed of repeating units of D-glucuronic acid and decreased the viability and proliferation of human
N-acetyl-D-glucosamine, is a highly hydrated polyanionic umbilical cord blood-derived mesenchymal stem cells in
macromolecule that mainly exists in the form of sodium vitro, they promoted the chondrogenetic differentiation
salt in nature. Sodium hyaluronate aqueous solution has both in vitro and in vivo in a pig model of cartilage
high viscosity and good shear thinning property [139] . repair. In addition to printing scaffolds for cell seeding,
However, hyaluronic acid hydrogel has low gelation rate in hydroxyapatite can also be printed with cells together using
the literature, and hyaluronic acid precursor solution was extrusion-based printing. For instance, adipose-derived
printed and crosslinked at 37°C for 4 hours [140] . In order to stem cells-laden hydroxyapatite/GelMA/methacrylated
improve the hydrogel crosslinking rate, hyaluronic acid is hyaluronic acid inks were bioprinted for a stable grid
often chemically modified to be photocrosslinkable [44,48,139] . structure at room temperature and cultured for 28 days [120] .
For example, hydrogel precursor containing pentenoate- The addition of hydroxyapatite showed positive effects on
functionalized hyaluronic acid, dithiothreitol, and Irgacure bone matrix production and remodeling. Hydroxyapatite
2959 was printed and then crosslinked after exposure is an important component for developing osteoinductive
to 312 nm UV light for 2 minutes. The poor mechanical bioink and widely used in bone tissue bioprinting research.
strength of hydrogel results in simple pattern structure.
Using hyaluronic acid blended with other hydrogels as 3.1.9. Conductive materials
biomaterial inks can improve printing fidelity to bioprint Conductive materials can be used as electrodes to
stable constructs. The compressive modulus of bioprinted promote signal transductions between biological tissues
hyaluronic acid/methylcellulose constructs increased with and electrical circuits. It is noteworthy to mention that
increasing methylcellulose contents . Human articular conductive materials can also promote cell adhesion,
[47]
chondrocytes encapsulated with hyaluronic acid/alginate proliferation, and differentiation by stimulation. Due
were co-printed with PLA to engineer cartilage tissue . to the potential, conductive materials have been used in
[45]
The mechanical properties of the bioprinted constructs smart biosensors, functional tissue engineering scaffolds,
were comparable to those of human articular cartilage and implants. In extrusion-based bioprinting applications,
after 4 weeks of in vitro culture. Human glial cells were conductive biomaterial inks can be formed by using different
bioprinted with hyaluronic acid/alginate/gelatin for conductive materials including conductive polymers
[142]
[112]
[143]
developing a brain matrix-mimetic microenvironment (e.g., polypyrrole , polyaniline [144] , polythiophene ,
model, which simulated both mechanical and biological and polyethylene dioxythiophene ), conductive metal
[145]
[146]
properties of human brain microenvironment [141] . nanoparticles (e.g., gold and silver ), conductive
carbon-based materials (e.g., carbon nanotube [147] and
3.1.8. Hydroxyapatite graphene [148] ), or ionic liquids [149] . Metal nanoparticles and
Hydroxyapatite, which is the main inorganic component carbon-based materials have long-term cytotoxicity, which
of bones, is mainly used to construct bone tissue by can be a limitation for tissue engineering and regenerative
bioprinting. Although hydroxyapatite cannot provide medicine [112] . Electrical conductivity is a key to native
natural binding sequences for cell attachment, it has tissue physiology and function of heart, brain, and nerve,
excellent biocompatibility, osteoconductivity, and so conductive hydrogels are often used for bioprinting
bioactivity, and it still belongs to category of bioactive cardiac and nervous tissues.
material. Hybrid hydroxyapatite-containing biomaterials 3.2. Mechanical support materials
provide a promotive scaffold for chondrocytes, facilitating Mechanical support materials are biocompatible, but they
the proliferation and migration of chondrocytes as well are generally biologically inert and not conducive to cell
as promoting the chondrogenic differentiation of stem adhesion. They are usually used as auxiliary materials to
cells [119] . As a heterologous material, hydroxyapatite is support bioprinting 3D structures. This section introduces
usually doped in other bioactive hydrogel materials, such nine representative mechanical support materials currently
as collagen, gelatin, GelMA, hyaluronic acid, and alginate, used in extrusion-based bioprinting.
to form an extrusion-based biomaterial ink. For example,
collagen/hydroxyapatite composite biomaterial ink was 3.2.1. Alginate
successfully used to print biomimic scaffolds seeded with Alginate is a natural polysaccharide extracted from brown
bone marrow stromal cells for bone regeneration [123] . By algae or Sargassum species. It forms a hydrogel through the
doping nanosized hydroxyapatite into weak printable rapid exchange reaction of calcium ions and sodium ions,
hydrogel, such as gelatin [119] and alginate [121] , the fluidity, and is widely used in the field of regenerative medicine.
viscosity, and gelation time were modulated to allow more The water-soluble, low-cost, and fast ionically crosslinked
freedom in 3D structure designs. Although the bioprinted gel forming properties of naturally sourced alginate make

Volume 9 Issue 2 (2023) 10 https://doi.org/10.18063/ijb.v9i2.649