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International Journal of Bioprinting Extrusion-based biomaterial inks

2.6. Molecular permeability structure, and ensure printability. Two or more biomaterials
The bioprinted 3D constructs need vascularized structure are often combined and selected to fulfill the printability
design to ensure the normal nutrient absorption and requirements of biomaterials inks and the needs of
waste excretion by shortening the distance between tissue bioactivity as well as achieve the balance among
mixed cells and culture medium. Biomaterial inks are biocompatibility, mechanical properties, and printability.
also required to have certain molecular permeability to The addition of a certain concentration of PEGDA
allow and maintain the transmission of macromolecular in GelMA can significantly increase the compression
proteins, small molecule drugs, and other active factors modulus of the printing structure and improve its
across the gel network. The swelling rate of the biomaterial mechanical property [127] . For example, adding nanoclay to
inks itself predicts the water content of the hydrogel and gelatin and alginate improves their printing performance,
the microscopic porosity inside the hydrogel. Molecular and cells grow well on the printed nanoclay composite
permeability is very important for cell migration and biomaterial scaffolds . According to their main functions
[26]
nutrient transport as the absorption and transmission from for biomaterial inks, biomaterial inks components can
cell culture medium to 3D construct could be affected. be divided into bioactive materials, mechanical support
materials, and rheological additives, as shown in Figure 4.
2.7. Bionic bioactivity Biomaterial inks usually have a variety of basic functions;
The combination of biomimetic components in bioprinted for instance, in addition to their bioactivity, gelatin
constructs plays a good role in cell attachment, migration, biomaterials are used as mechanical supports to support
proliferation, differentiation, and function. Bioactive tissue growth, and play a vital role in specific tissue type or
materials provide a highly biomimetic environment that printing process. Therefore, we classify the biomaterial inks
influences the size, shape, and adhesion of cells and according to their prominent functional characteristics,
[31]
comprise many matrix nutriments essential for cellular general preference of researchers, and previous literatures.
activities. ECM is the 3D natural microenvironment of Here, we mainly discuss the main function of materials
cells in vivo and have a positive effect on controlling cell used for extrusion-based biomaterial inks.
proliferation and differentiation. The biomaterial inks with
high similarity to ECM, and even tissue-specific ECM 3.1. Bioactive materials
components, should be prioritized with the aim to improve Bioactive materials are used to simulate ECM, usually one
their bionic biological activity. or more components of ECM or their derivatives. They
have great biocompatibility without cytotoxic effect and
3. Classification immune safety problems and can efficiently promote cell
activity and biological function. This section introduces
Extrusion-based biomaterial ink can be a single nine representative bioactive materials currently used in
component or a composite of multiple components, and extrusion-based bioprinting.
its components can be classified into five types according
to their sources. The first type is the natural dECM, such 3.1.1. Organ-derived dECM
as commercialized Matrigel [30,32,33] and organ-derived Organ-derived dECM is considered the ideal biomaterial
dECM [23,34-39] . The second type is the natural polymer ink, which retains most of the active components in the ECM
derivatives, which are divided into polysaccharides and of tissues and organs. The physical crosslinking of dECM is
proteins, such as collagen [40-43] , hyaluronic acid [44-48] , temperature-dependent and irreversible. Despite its poor
alginate [29,49-53] , chitosan [54-60] , fibrin [61-65] , silk [66-68] , gellan mechanical property, dECM solution forms gel in 30 minutes
gum [69-73] , guar gum [74,75] , carrageenan [76-78] , agarose [79-81] , after an increase of the temperature from 4°C to 37°C. The
gelatin [82-88] , gelatin methacrylate (GelMA) [22,89-94] , cellulose structure of using dECM to perform printing alone is just
derivatives [95-99] , etc. The third type is the synthetic a simple pattern with low resolution. Thus, combinatory
polymers, in either hydrogel form or hot melt type, dECM biomaterial inks are more reported to construct 3D
[23]
such as polyethylene glycol (PEG) [100-103] , PEGDA [104, 105] , structure . For example, the rheological properties and shear
Pluronic [106-110] , polycaprolactone (PCL) [111-113] , polylactic thinning properties of human skin-dECM were improved
[34]
acid (PLA) [114-116] , poly (lactic co glycolic acid) (PLGA) [117,118] , through supplementation with fibrinogen hydrogel . The
etc. The fourth type is the inorganic materials, such as basic alginate/gelatin bioink with 0.5 and 1 mg/mL human
hydroxyapatite [119-123] and nanoclay [26,124-126] . The fifth type is lung dECM showed the desirable viability and metabolic
[36]
the semiconductor materials. Table 1 lists the commonly functions of the printed HepaRG cells .
used biomaterial inks in extrusion-based bioprinting.
3.1.2. Commercial dECMs
Different components perform different functions, Matrigel, Geltrex, and BME are commercial decellularized
mainly to provide bioactivity, maintain mechanical extracellular matrix gel of Corning, Invitrogen, and R&D

Volume 9 Issue 2 (2023) 6 https://doi.org/10.18063/ijb.v9i2.649