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International Journal of Bioprinting 3D printed hydrogels for tumor therapy

Keywords: 3D printing; Magnesium; Anti-tumor effect; Bone tissue regeneration; Controlled release

1. Introduction its remarkable ability in constructing customized and
patient-specific scaffolds that closely mimic the intricate
Osteosarcoma, a malignant bone tumor, is typically and complex anatomical structures of native tissues. 17–19
managed through surgical resection in clinical practice. Numerous 3D-printed scaffolds have been extensively
1
However, incomplete removal of tumor cells often leads designed and employed to repair bone tissues in preclinical
to tumor recurrence. Consequently, chemotherapy and and clinical trials. For example, some 3D-printed metallic
radiotherapy are commonly employed post-surgery to scaffolds (e.g., stainless steel, titanium) have been used
eradicate residual tumor cells. Nevertheless, previous in clinical practice for bone tissue engineering. Among
2,3
20
studies have indicated that these non-targeted approaches various 3D-printed scaffolds, gelatin methacryloyl
may result in side effects such as damage to normal cells (GelMA)-based hydrogels and hydroxyapatite (HAp)-
and drug resistance development. To overcome these based scaffolds have shown great potential in bone tissue
limitations, the development of an on-site controlled drug engineering. 21–23
release system mediated and assisted by photothermal
therapy (PTT) is crucial for minimizing drug dosage and GelMA is a popular biomaterial for 3D printing. 24,25
avoiding cytotoxicity while enhancing therapeutic efficacy It is an engineered gelatin-based biomaterial synthesized
in tumor treatment. Photothermal agents play an essential through the methacrylation of the lysine groups in the
4,5
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role in achieving effective PTT by inducing hyperthermia gelatin backbones. As a result, GelMA exhibits great
at cancerous site and simultaneously modulating drug similarity to gelatin in terms of excellent biocompatibility,
release upon near-infrared (NIR) laser irradiation, thereby biodegradability, and temperature-responsive behavior,
effectively eradicating residual tumor cells and enhancing as well as the presence of Arg-Gly-Asp (RGD) sequences,
antitumor efficacy. Among various photothermal agents, which facilitate cell adhesion. Additionally, GelMA
6,7
such as gold nanoparticles, copper nanoparticles, magnetic possesses good photo-crosslinking ability and can be
iron-oxide nanoparticles, and carbon-based nanomaterials, covalently crosslinked with water-soluble photoinitiators
polydopamine (PDA) nanoparticles have attracted when exposed to visible or ultraviolet (UV) light, thereby
significant interest in tissue engineering and controlled forming stable hydrogel networks. Therefore, 3D-printed
drug release due to their remarkable biocompatibility, GelMA hydrogels have gained significant attention in
biodegradability, and excellent photothermal property. 8,9 bone tissue engineering. 27,28 For example, Zhang et al.
Furthermore, the abundant catechol and amine groups demonstrated that 3D-printed reduced graphene oxide
of PDA nanoparticles confer excellent adhesive capability (rGO)/GelMA hydrogels could enhance osteogenic
that facilitates high drug loading efficiency. In this context, and neurogenic dual differentiation simultaneously for
many studies have employed PDA nanoparticles for potential neutralized bone regeneration. However, it
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encapsulating diverse drugs and biomolecules in tissue should be noted that GelMA inks often exhibit poor
engineering and cancer therapy applications. 10,11 printability and the resulting GelMA hydrogels possess
inadequate mechanical strength, posing challenges for 3D
Resection of a bone tumor inevitably results in bone
defects post-surgery. Despite the inherent self-regeneration printing and bone tissue regeneration.
ability of native bone tissue, three-dimensional (3D) tissue Many efforts have been devoted to improving the
engineering scaffolds are preferred to be used to significantly printability of GelMA inks and enhancing the mechanical
accelerate the healing process of bone defects. 12,13 Tissue performance of 3D-printed GelMA hydrogels. 25,30
engineering scaffolds possess 3D structures that mimic the Generally, incorporating ceramic nanoparticles in
anatomical characteristics and provide essential functions GelMA hydrogels has proven effective in addressing
of targeted tissues through the combination of suitable these challenges. 31,32 HAp—a bioceramic known
biomaterials and cells, along with the incorporation for its exceptional biocompatibility, bioactivity, and
of appropriate biomolecules, and therefore have been osteoconductivity—is widely used as a bone substitute
widely used for treating bone defects. 14–16 Compared to biomaterial, and HAp-based scaffolds have demonstrated
conventional 3D scaffold manufacturing technologies, significant potential in bone tissue regeneration.
i.e., solvent casting/particle leaching, freeze-drying, Previous studies have indicated that 3D-printed HAp/
gas forming, thermal-induced phasing separation, and GelMA hydrogels could improve the printability of inks,
electrospinning, 3D printing technology significantly enhance mechanical strength, and promote bone tissue
enhances the potential in regenerating tissues due to regeneration. For example, Song et al. demonstrated
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Volume 10 Issue 5 (2024) 233 doi: 10.36922/ijb.3526