Page 145 - IJB-7-3

Zhou, et al.
Aqueous solutions of some ABA triblock copolymers, been used to improve the printability of polymers such as
consisting of hydrophobic A and hydrophilic B blocks, will gelatin , sodium alginate , silk fibroin , hyaluronic
[46]
[45]
[14]
undergo a reversible sol-gel-sol transition with the increase acid [15,17] , and PEG [3,41,47] , is a good choice due to its rapid
of temperature [19-22] . One of the most commonly used solidification and controllable gelation by ultraviolet (UV)
copolymers is comprised of PEG as hydrophilic blocks and radiation.
aliphatic polyester as the hydrophobic units. The polyester In this study, the thermo-sensitive and photo-
blocks can be poly(lactide-co-glycolide) (PLGA) [21,23] , sensitive hydrogels based on triblock copolymers PLGA-
poly(caprolactone-co-lactide) [19,24] , poly(caprolactone- PEG-PLGA were explored as inks. To obtain the dual-
co-glycolide) (PCGA) [25] , polycaprolactone and so sensitive hydrogels, the copolymers were first synthesized
[20]
on. At low temperatures, the triblock copolymers self- by ring-opening polymerization, followed by esterification
assemble into “flower-like” micelles and the solutions of the hydroxyl group with acrylic acid (Figure S1). The
behave like liquid . When the temperature is elevated, thermo-induced gelation was used to adjust the rheological
[26]
micelles aggregate to form a percolated network through properties of the hydrogels, yielding a printable ink
hydrophobic interactions, resulting in a gel at the that could hold its predesigned shapes during extrusion.
macroscopic level [22,27] . With many parameters such as Afterward, the printed scaffolds were fixed by UV
block length of PEG and polyester , molecular weight photopolymerization crosslinking with the enhancement
[28]
distribution [21,23] , end group , and even addition agent of physical strength. A variety of constructs, including a
[29]
[28]
can be used to adjust the sol-gel transition behavior. human nose, were successfully printed with high shape
For their fast sol-gel transition between room and body fidelity through the two-step crosslinking strategy.
temperature, these thermogels have been demonstrated Moreover, by mixing with unmodified copolymers
potential applications as injectable hydrogels in drug (Figure 1A), the mechanical properties, swelling ratio,
delivery systems [30,31] , tissue engineering [32,33] , and and printability of inks could be easily tailored without
prevention of post-operative adhesion . compromising their extrudability. It is believed that this
[24]
We believe the thermal-sensitive copolymers dual-sensitive hydrogel can be used as bioinks for printing
hydrogel may serve as a promising candidate for large tissue-like constructs in the future.
bioink because of its excellent biodegradability and
biocompatibility . However, an ideal ink should fulfill 2. Materials and methods
[34]
certain rheological and mechanical requirements to 2.1. Materials
achieve good extrudability as well as high shape fidelity.
That is, it is required that the inks not only can be PEG with a number-average molecular weight of
extruded easily as a smooth and uniform filament but also 1500 Da (PEG1500) was purchased from Sigma-
can maintain sufficient mechanical strength to support Aldrich (St. Louis, USA). The monomers L-lactide
the printed structure without collapse [20,22] . Although the and glycolide were gifted by Medsun (Hangzhou,
thermogels can be extruded as a fiber , their mechanical China). N,N’-dicyclohexylcarbodiimide (DCC),
[35]
strength is still too weak to support large complicated 4-dimethylaminopyridine (DMAP), acrylic acid, and
objects. Therefore, it is desired to improve the mechanical tin 2-ethylhexanoate [Sn(Oct) ] were obtained from
2
strength of the hydrogel to meet the need of 3D printing. Aladdin (Shanghai, China). The photoinitiator, lithium
At present, the introduction of new cross-linking phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) was
mechanisms such as host-guest interaction [15,36,37] , metal received from TCI (Tokyo, Japan). Anhydrous diethyl
ions coordination , photopolymerization [10,39,40] , chemical ether, methylene dichloride (DCM), and other chemicals
[38]
coupling reaction [41,42] , and enzyme-catalyzed reaction [16,43,44] were all chemical regent grade and bought from Shanghai
is the most common way to enhance the physical strength of Chemical Reagents Co. (Shanghai, China). PEG1500 was
inks. The thermo-sensitive physical hydrogel could also be dehydrated before the experiments, and other reagents
strengthened through the formation of new crosslinks. For were all used as received.
example, Ohya’s group decorated the triblock copolymer 2.2. Synthesis of the triblock copolymer
PCGA-PEG-PCGA with succinimide ester groups at the
termini and then crosslinked with polyamines. However, The triblock copolymers PLGA-PEG-PLGA were
the modified copolymers were insoluble in water and synthesized by ring-opening copolymerization of L-LA
a crosslinking agent was needed to form a covalent and GA in the presence of PEG1500 as an initiator and
network. Most importantly, nearly no improvement on Sn(Oct) as a catalyst (Figure S1). The detailed synthesis
2
modulus was observed due to the low reaction efficacy . procedure of P1 was shown as following. Dehydrated
[25]
Thus, it is desired to provide the thermogels with a more PEG1500 (7.5 g, 5 mmol), L-LA (11.4027 g, 68.69 mmol),
effective crosslinking to enhance their physical strength. GA (9.1855 g, 68.69 mmol), and Sn(Oct) (3 – 5 drops)
2
The photopolymerization crosslinking system, which has were weighed and added to a 250-mL round-bottom flask.
International Journal of Bioprinting (2021)–Volume 7, Issue 3 141