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International Journal of Bioprinting 4D printing & simulation for biomedicine

in 4D printing undergo changes in shape or function its thermomechanical properties revealed a glass
over time within a specific environment and in response transition temperature (T ) within the body temperature
g
to stimuli. Therefore, an ideal printed structure produced range, and dynamic mechanical analysis (DMA) was
by 4D bioprinting should have the ability to respond to performed. The processability of the material by 3D
such dynamism for effective integration with the human printing was confirmed through printability tests, and
body. 2,4-8 Furthermore, with minimal invasiveness biodegradability characteristics were assessed using an
and appropriate responses to human elements, there accelerated decomposition method. Biocompatibility
is considerable potential for applications in precision was established by investigating the interaction between
medicine, offering personalized treatments for the developed material and cells in a series of in vitro
individual patients. 9-13 experiments. The experimental results verified that
Smart materials, including shape-memory polymers the developed material underwent shape deformation
(SMPs), shape-memory alloys (SMAs), and hydrogels, into the programmed shape in a specific stimulation
are utilized to enable programmed changes in shape over environment. Furthermore, a simulation study was
time in specific conditions. 14-17 Several characteristics of conducted to enable theoretical prediction of its shape.
smart materials are particularly vital for their application This study demonstrated that sophisticated shapes
in 4D bioprinting within the medical field. For suitability tailored to the individual characteristics of each patient
in 4D printing, the material should demonstrate flexible can be fabricated with 4D printing and highlighted the
expansion and contraction in response to a specific ability to accurately predict shape recovery occurring
stimulus, ensuring it is nonharmful to the human body. in programmed shapes. This material will enhance
Additionally, the material must be easy to process, the performance of medical devices, such as catheters,
facilitating the manufacture of complex geometries stents, and artificial scaffolds.
tailored to the patient’s characteristics. Furthermore,
during the treatment period, metabolic interactions with 2. Materials and methods
surrounding human tissue are crucial, necessitating the 2.1. Materials
use of materials that can be safely absorbed into the body Poly(lactic acid) (PLA) was sourced from PLA (Green
at the appropriate time. 9,18-20 Chemical Co., South Korea), while polyethylene glycol
To utilize 4D printing in precision medicine, it is (PEG) was obtained from PEG (Samchun Co., South Korea).
crucial not only to design a well-formed programmable 2.2. Preparation of body temperature-responsive
structure but also to accurately predict the time- shape-memory polymers
dependent behavior resulting from specific stimuli. Prior to extrusion, PLA and PEG were oven-dried at
4D printing is well-suited for applications within the 45°C for 4 h. PLA and PEG were combined in plastic
human body, where it will be subjected to continuous bags and mixed using a tumbler mixer. The blend was
change. Therefore, there is increasing interest in 4D then fed at a rate of approximately 4 kg/h into the main
bioprinting simulations, which are crucial for achieving hopper of a corotating intermeshing twin-screw extruder
4D-printed biomaterials with the desired mechanical (STS25–44V–SF; Hankook EM Ltd., South Korea), set at
properties and structural integrity. 21-23 Simulation allows a hopper temperature of 100°C. This extruder features
researchers and medical professionals to anticipate how a screw diameter of 25 mm and a length-to-diameter
printed structures will respond within the dynamic (L/D) ratio of 44. It is equipped with two die holes,
environment of the body, aiding in the optimization of each 4 mm in size, and operates at a screw speed of 180
designs and materials for enhanced biocompatibility rpm. The barrel temperature was maintained at 100–
and functionality. Thus, integrating 4D bioprinting 207°C to achieve a resin temperature of 225°C, slightly
simulations into the design and development process exceeding the barrel temperature due to internal friction
is essential for advancing the efficacy and reliability of and shearing effects. The pressure within the barrel was
precision medicine applications. kept at 10 bar. The melted resins were cooled in a water

In this study, an SMP was developed to maintain bath at room temperature (22–24°C) and subsequently
shape-memory effects and self-deformation pelletized. The pellets were then oven-dried at 35°C for 24
characteristics as a 4D printing material. This polymer h. For specimen preparation, the composite pellets were
demonstrated excellent processability with a 3D printer processed in an injection molding machine (LGH50N; LS
and exhibited biocompatibility and biodegradability Mtron Co., South Korea) with a screw diameter of 25 mm.
through synthesis from polylactic acid (PLA) and The machine was operated at barrel temperatures of 220–
polyethylene glycol (PEG) (Figure 1). Analysis of 230°C, with a maximum injection pressure of 2520 kgf/

Volume 10 Issue 3 (2024) 573 doi: 10.36922/ijb.3035