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3D-Printed Anti-Tumor Scaffolds
of the spleen showed that the injection group had obvious intraperitoneal injection. The implanted PLA/MTX
white hyperplasia and more inflammatory cells (B-cell scaffolds can release and maintain therapeutic drug
monocytes, etc.). There was no obvious nephrotoxicity levels at the tumor site for prolonged time while
found in all four groups. reducing systemic drug exposure to healthy tissues.
Moreover, this implantable scaffold only requires 1 time
4. Discussion implantation, which greatly reduces the frequency of
As shown in Figure 8, under the guidance of computer- drug administration. Therefore, PLA/MTX scaffold as a
aided design (CAD) and 3D printing technology, PLA/ controllable drug delivery system has great potential for
MTX drug-loaded scaffold was prepared by FDM printer. suppressing tumor growth.
Then, PLA/MTX drug-loaded scaffold was implanted 5. Conclusions
into the mouse body. With the release of MTX, the
growth and reproduction of tumor cells were inhibited. We developed a novel 3D-printed drug delivery scaffold
The drug release from the PLA/MTX scaffold showed for tumor therapy. Morphological and structural analysis
a sustained and slow process due to the degradation results showed that MTX was successfully incorporated
process of PLA . The CCK-8 assay demonstrated that into the PLA filament. PLA/MTX scaffolds can maintain
[39]
the PLA material did not exert severe cytotoxic effects on MTX release for more than 30 days. In vitro cytotoxicity
4T1, A549, MCF-7, MG-63, and MC3T3 cells. In vitro experiments confirmed that PLA/MTX scaffolds have
cellular experiments revealed that the printed PLA/ a relatively high inhibitory effect on tumor cells while
MTX scaffolds have a relatively high inhibitory effect showing less toxicity to normal cells. In addition, in vivo
on the tumor cells MG-63, A549, MCF-7, and 4T1, and results demonstrated that the PLA/MTX scaffolds highly
lower toxic effect on the normal cells MC3T3-E1. The suppressed tumor growth with negligible side effects on the
inhibition rates of three different concentrations of PLA/ normal tissues and organs. 3D-printed PLA/MTX scaffolds
MTX scaffolds on cancer cells were more than 95% after could be used as a controllable drug delivery system and
cultured for 5 days. have the great potential for suppressing tumor growth.
After 3 weeks of observation, PLA/MTX scaffold
with different MTX concentrations group had a higher Funding
tumor inhibition rate. We found that PLA/MTX scaffold This research was supported by Technology Department
was better than MTX injection in controlling tumor growth. of Yangzhou City (YZ2019073) from Jiangsu Huadong
This was attributed to an enrichment of the released MTX Medical Device Industrial Co., Ltd., China. A project
around the tumor tissue and lasting therapeutic MTX funded by the Priority Academic Program Development
levels for prolonged time. The intraperitoneal delivery of of Jiangsu Higher Education Institutions, Guangxi Natural
MTX needed injection of drug every 2 days while PLA/ Science Foundation (2019JJA140071), and the First
MTX scaffold was implanted only once for the treatment, Batch of High-level Talent Scientific Research Projects
indicating that the PLA/MTX drug delivery system was of the Affiliated Hospital of Youjiang Medical University
more efficient than traditional injection method. for Nationalities in 2019 (Contract No. R20196307).
In a word, 3D-printed PLA/MTX scaffolds
maintained a high tumor inhibition rate and significantly Conflicts of interest
reduced systemic drug toxicity compared with
The authors declare that they have no conflicts of interest.
Authors’ contributions

P.Z., C.H., and Y.M. conceived the project. Y.M. and C.H.
conducted the scaffold fabrication and characterization.
C.H. and C.G. conducted the cell and animal study.
P.Z. reviewed the experimental results and advised the
organization of the main contents. P.Z., G.L., H.L, C.G.,
and Y.M. wrote the manuscript.

References

1. O’Reilly M, Mellotte G, Ryan B, 2020, Gastrointestinal Side
Effects of Cancer Treatments. Ther Adv Chronic Dis, 11:1-7.
Figure 8. Schematic illustration of the fabrication and application https://doi.org/10.1177/2040622320970354
of PLA/methotrexate scaffolds for tumor therapy. 2. Nandini D B, Rao R S, Hosmani J, et al., 2020, Novel

142 International Journal of Bioprinting (2021)–Volume 7, Issue 4