Page 159 - IJB-9-1

International Journal of Bioprinting Bio-inks for 3D printing cell microenvironment

modification. The content of proline and hydroxyproline PCL, for example, has a slow degradation rate. The
in fish gelatin is lower than that of pork gelatin, but the copolymerization of PCL with other monomers can meet
content of threonine and serine is higher . The differences the requirements for optimally controlled mechanical
[60]
in amino acid and peptide compositions can affect spatial properties in tissue engineering . When PCL is combined
[63]
conformation and confer different mechanical properties with PLGA copolymers, the degradation rate increases.
to biomaterials derived from different sources. It takes time for cells to adhere to and spread on
The mechanical properties of bio-inks are also the scaffold material. Using cell-loaded bio-inks and
determined by the arrangement and assembly of molecules. collaborating with the scaffold would not only temporarily
In view of its highly ordered spatial structure, collagen fix the cells’ spatial position in case of loss, but also mimic
imparts extremely high mechanical properties to tendons the solid–liquid bidirectional microenvironment at the
and ligaments . Despite being derived from tendons, junction of certain tissues.
[61]
in vitro collagen hydrogel fabrication based on pH and
irreversible chemical cross-linking (e.g., genipin) cannot 4. Basic mechanical microenvironment and
replicate the high strength of native tendons . Similar bio-inks
[61]
problems arise in ECM extracts, such as Matrigel, whose As a substitute for ECM in vitro, the performance of bio-
gel strength is an order of magnitude lower than ideal ink should be compared with the cell microenvironment
materials and is greatly influenced by the donor source .
[62]
in vivo as a standard. Therefore, in in vitro experiments,
3.2. Non-hydrogel bio-inks the mechanical properties of bio-ink themselves are as
Most hydrogel bio-inks can either encapsulate cells or act important as the matrix mechanical microenvironment. In
as adhesive scaffolds. This section only discusses non- current research context, the mechanical characterization
hydrogel materials for scaffolds. Typically, such materials of living tissue is applicable in the mechanical
cannot be loaded with cells because the manufacturing microenvironment of bio-inks, such as stiffness, stress
process of scaffold is unsuitable for cell survival. As a relaxation, etc.
result, they are not always discussed in conjunction with 4.1. Static mechanical microenvironment
bio-inks. However, as the performance of extrusion-based Static mechanics are basic conditions that do not change
bioprinters has improved in recent years, some scaffold with time. The static mechanical microenvironment, as
materials can be processed together with bio-inks. Also, a highly researched mechanical cue, is relatively easy
the fact that scaffold materials play an inseparable role in to realize. As the most basic, initial stiffness is a fairly
the mechanical microenvironment is important.
controllable variable, in which many natural or synthetic
Aliphatic polyesters are considered a type of scaffold polymer materials can perform this task well.
material that is commonly used in 3D bioprinting. They Osteocytes require a microenvironment with high
have become one of the most widely used biopolymers in the initial stiffness, in particular, the differentiation of
biomedical field due to their non-toxicity, biodegradability, osteoblasts. For environments with high initial stiffness,
and good biocompatibility. Natural compounds such as aliphatic polyesters, such as PCL, polylactic acid, PGA, and
lactide, glycolide, and ε-caprolactone are used to make PDO, which are printed by high-temperature extrusion
aliphatic polyesters . Common polyesters are polylactic and have modulus with GPa level, allow the approximation
[63]
acid, polyglycolide (PGA), poly(ε-caprolactone) (PCL), of the stiffness of bone tissue and cell adhesion without
poly(γ-valerolactone), polydioxone (PDO), and their modification . These materials have different mechanical
[66]
copolymers, such as poly(lactic-co-glycolic acid) (PLGA). properties and degradation rates according to the variation
The ester functional groups in the (co)polymer backbones of in composition and molecular weight. In general, PGA
aliphatic polyesters can be hydrolyzed by enzymes, resulting has a higher stiffness (>7 GPa), while PDO is relatively
in water and carbon dioxide as degradation products . This soft (1–2 GPa) . During bioprinting, due to their similar
[64]
[66]
means that aliphatic polyesters can be eroded by cells. thermoplastic properties, aliphatic polyesters can be mixed
Aliphatic polyesters are thermoplastic and can be in different proportions as required, blended with other
formed into highly precise structures using the printers’ functional components, or chemically modified to achieve
controlled extrusion. The temperature of fabrication varies different molding conditions and specific needs. When
by composition and molecular weight, with relatively simulating bone tissue, structural design is as important
controllable rates of degradation. The melting point of as material stiffness. According to studies, the hardness of
aliphatic polyesters increases with crystallinity, and their cancellous bone is 12% less than that of adjacent compact
[67]
degradation rate decreases with hydrophilicity, which also bone; this is not entirely due to content difference .
affect their mechanical properties . Semi-crystalline Stiffness tests in various directions are required, owing to
[65]
Volume 9 Issue 1 (2023) 151 https://doi.org/10.18063/ijb.v9i1.632