Hydrogel-Based Bioinks for Coaxial and Triaxial Bioprinting: A Review of Material Properties, Printing Techniques, and Applications

Abstract

Three-dimensional bioprinting technology has emerged as a rapidly advancing multidisciplinary field with significant potential for tissue engineering applications. This technology enables the formation of complex tissues and organs by utilizing hydrogels, with or without cells, as scaffolds or structural supports. Among various bioprinting methods, advanced bioprinting using coaxial and triaxial nozzles stands out as a promising technique. Coaxial bioprinting technique simultaneously deposits two material streams through a coaxial nozzle, enabling controlled formation of an outer shell and inner core construct. In contrast, triaxial bioprinting utilizes three material streams namely the outer shell, inner shell and inner core to fabricate more complex constructs. Despite the growing interest in 3D bioprinting, the development of suitable cell-laden bioinks for creating complex tissues remains unclear. To address this gap, a systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) flowchart, collecting 1621 papers from various databases, including Web of Science, PUBMED, SCOPUS, and Springer Link. After careful selection, 85 research articles focusing on coaxial and triaxial bioprinting were included in the review. Specifically, 77 research articles concentrated on coaxial bioprinting and 11 focused on triaxial bioprinting, with 3 covering both techniques. The search, conducted between 1 April and 30 September 2023, had no restrictions on publication date, and no meta-analyses were carried out due to the heterogeneity of studies. The primary objective of this review is to assess and identify the most commonly occurring cell-laden bioinks critical for successful advancements in bioprinting technologies. Specifically, the review focuses on delineating the commonly explored bioinks utilized in coaxial and triaxial bioprinting approaches. It focuses on evaluating the inherent merits of these bioinks, systematically comparing them while emphasizing their classifications, essential attributes, properties, and potential limitations within the domain of tissue engineering. Additionally, the review considers the applications of these bioinks, offering comprehensive insights into their efficacy and utility in the field of bioprinting technology. Overall, this review provides a comprehensive overview of some conditions of the relevant hydrogel bioinks used for coaxial and triaxial bioprinting of tissue constructs. Future research directions aimed at advancing the field are also briefly discussed.

Keywords: bioprinting; coaxial and triaxial bioprinting; hydrogel bioinks; tissue engineering.

Figure 1

The three major components of tissue engineering.

Figure 2

Human tissues and organs that could benefit from tissue engineering for transplantation.

Figure 3

Three-dimensional bioprinting techniques: (i) laser-based, (ii) inkjet-based, (iii) stereolithography-based, and (iv) extrusion-based. Bioprinting of tissues may provide a solution for organ shortages.

Figure 4

Conventional extrusion-based bioprinting conditions: (a) shear-thinning, (b) printing in a coagulation bath, and (c) printing in a support bath.

Figure 5

The desired features of bioinks.

Figure 6

Schematic representation of nozzle types used in bioprinting: (a) monoaxial nozzle (b) coaxial nozzle (c) triaxial nozzle.

Figure 7

PRISMA flow chart illustrating the literature research, exclusion step, screening process, and the final included papers. Eighty-five research articles were accepted with no publication date restriction (search performed from 1 April 2023 to 30 September 2023). n in the flow chart represents total number.

Figure 8

Upward trend in research articles for coaxial and triaxial bioprinting using an Origin ribbon chart (total number of appearances per year). The coaxial and triaxial bioprinting research articles are shown individually in purple and green colors, respectively.

Figure 9

Schematic representation of three distinct bioprinting phases: (a) pre-printing (material and cell selection, hydrogel synthesis, and hydrogel development); (b) coaxial and triaxial bioprinting (parameters and crosslinking methods); (c) post-printing experiments (cellular studies and mechanical tests).

Figure 10

Commonly used hydrogels for cell-based 3D bioprinting. Polymers without bold font have been used for 3D bioprinting, whereas polymers in bold and italics have been explored in coaxial and/or triaxial bioprinting [71].

Figure 11

Chemical structure of alginate.

Figure 12

Chemical structures of: (a) gelatin, (b) Gel–MA, and (c) Gel–TA (circles represent individual amino acids).

Figure 13

Chemical structures of: (a) HA, (b) HA–MA, and (c) HA–TA.

Figure 14

Chemical structures of: (a) PEG and (b) PEG–TA.

Figure 15

Chemical structure of Pluronic F-127.

Figure 16

The concentration of the most commonly used materials for coaxial and triaxial bioprinting: (a) Alginate and its combinations. (b) Gelatin and its combinations. (c) Gel–MA and its combinations. (d) PEG with its derivatives and Pluronic F-127.

Figure 17

Coaxial nozzle. (A) Equal needle-length tips. (B) Shorter inner core needle length: (i) outer diameter of the outer shell (ii) inner diameter of the outer shell (iii) inner diameter of the inner core (iv) outer diameter of the inner core (v) arc of the filament section and (vi) length of the printed filament section.

Figure 18

Triaxial nozzle. Equal needle-length tips: (i) outer diameter of the outer shell (ii) inner diameter of the outer shell (iii) inner diameter of the inner shell (iv) outer diameter of the inner shell (v) inner diameter of the inner core (vi) outer diameter of the inner core (vii) arc of the filament section and (viii) length of the printed filament section.