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International Journal of Bioprinting


                                        RESEARCH ARTICLE
                                        3D-printed PNAGA thermosensitive hydrogel-

                                        based microrobots: An effective cancer therapy
                                        by temperature-triggered drug release



                                        Yan Zhou, Min Ye, Hongyu Zhao, Xiaopu Wang*

                                        Shenzhen Institute of Artificial Intelligence and Robotics for Society (AIRS), The Chinese University
                                        of Hong Kong, Shenzhen, Guangdong 518129, China



                                        Abstract

                                        Hydrogels  with  temperature-responsive  capabilities  are  increasingly  utilized  and
                                        researched  owing  to  their  prospective  applications  in  the  biomedical  field.  In
                                        this work, we developed thermosensitive poly-N-acryloyl glycinamide (PNAGA)
                                        hydrogels-based microrobots by using the advanced two-photon polymerization
                                        printing technology. N-acryloyl glycinamide (NAGA) concentration-dependent
                                        thermosensitive performance was presented and the underlying mechanism behind
                                        was discussed. Fast swelling behavior was achieved by PNAGA-100 at 45°C with a
                                        growth rate of 22.5%, which is the highest value among these PNAGA hydrogels.
                                        In addition, a drug release test of PNAGA-100-based thermosensitive hydrogels was
                                        conducted. Our microrobots demonstrate higher drug release amount at 45°C (close
                                        to body temperature) than at 25°C, indicating their great potential to be utilized in
                                        drug delivery in the human body. Furthermore, PNAGA-100-based thermosensitive
            *Corresponding author:      microrobots are able to swim along the route as designed under the magnetic
            Xiaopu Wang                 actuator after incubating with Fe@ZIF-8 crystals. Our biocompatible thermosensitive
            (wangxiaopu@cuhk.edu.cn)
                                        magnetic microrobots open up new options for biomedical applications and
            Citation: Zhou Y, Ye M, Zhao H,   our work provides a robust pathway to the development of high-performance
            et al., 2023, 3D-printed PNAGA   thermosensitive hydrogel-based microrobots.
            thermosensitive hydrogel-based
            microrobots: An effective cancer
            therapy by temperature-triggered
            drug release. Int J Bioprint, 9(3):   Keywords: 3D printing; PNAGA thermosensitive hydrogel; Swelling; Drug release;
            709.                        Magnetic microrobot
            https://doi.org/10.18063/ijb.709
            Received: November 8, 2022
            Accepted: December 22, 2022
            Published Online: March 15, 2023  1. Introduction
            Copyright: © 2023 Author(s).
            This is an Open Access article   Recent years have witnessed increasing interest in developing hydrogels because of their
            distributed under the terms of the   good  mechanical  properties,  hydrophilicity,  and  biocompatibility [1-7] .  Temperature-
            Creative Commons Attribution   responsive hydrogels, which can autonomously change physical and/or chemical
            License, permitting distribution
            and reproduction in any medium,   properties when temperature changes, are the research frontier of advanced functional
            provided the original work is   materials science [8-11] . A  series of  temperature-responsive  thermosensitive hydrogels
            properly cited.             have been reported in recent years [12-14] . Poly(n-isopropylacrylamide) (pNIPAM) is one
            Publisher’s Note: Whioce    of the prime examples with a low critical solution temperature (LCST) value close to
            Publishing remains neutral with   human body temperature and exhibits obvious shrinkage properties around an LCST
            regard to jurisdictional claims in
            published maps and institutional   of ~32°C. pNIPAM has been widely used in many fields, such as drug delivery, tissue
            affiliations.               regeneration and artificial muscles [15-19] .



            Volume 9 Issue 3 (2023)                        272                         https://doi.org/10.18063/ijb.709
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