Hunter Mansfield

Introduction:  Osteosarcoma is the most common malignant tumor bone, and can affect any bone in the body but primarily affects the long bones. The condition is rare, with only about 900 cases diagnosed per year, 45% of which being children.¹ Osteosarcoma is heavily associated with ionizing radiation exposure and inherited mutations such as Paget’s, Li Fraumeni, hereditary retinoblastoma, Bloom Syndrome, or Werner Syndrome. Osteosarcoma is diagnosed via physical exam and plain radiographs and is almost always treated with surgical resection, often with adjunct chemotherapy.² Traditional resection methods result in amputation and severe disfigurement, rendering patients handicapped for their entire lives. A solution gaining recent popularity is 3D printing; advances in 3D printing technology have enabled for more dynamic and treatment plans that allow for almost complete limb and function salvage.³ Methods:Vario us compositions of bone grafts were 3D printed and then subjected to mechanical and animal testing. Grafts tested include poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PLGA/TCP) with and without an rhBMP-2 growth factor surface coating⁴, Hydroxyapatite coated polyetheretherketone (PEEK)-based bone scaffold immersed in antimicrobial and chemotherapy drugs⁵, and titanium 3D-printed bone scaffolds with drug-laden gelatin and hydroxyapatite.⁶  Results: In the grafts with PLGA/TCP, glucose uptake was greatly increased in the group with the rhBMP-2.  However, bone formation was not enhanced significantly. The best mechanical performance was seen in pure TCP scaffolds with rhBMP-2 coat. The scaffolds immersed in antimicrobial and chemotherapy drugs showed appropriate mechanical properties along with total eradication of E. coli and MRSA, as well as ablation of osteosarcoma cells. The titanium 3D-printed bone scaffolds with drug-laden gelatins provided a method for sustained release of bone-regenerative medicine as well as chemotherapy. This scaffold was also classified as “multifunctional” due to its ability to provide on-demand localized photothermal conversion for an in-vitro cancer ablation. Use of adjunct NIR irradiation was also shown to sensitize osteosarcoma cells and bacteria to laden chemotherapy and antibiotics.^4,5,6  Conclusions: Now that 3D printed bone grafts have started to show efficacy with more traditional implant materials such as titanium, research is now moving towards materials more unique to 3D printing as well as customizing parameters unique to additive manufacturing such as porosity and composite scaffolds. Additionally, more bioactive substances are showing promise, including hydroxyapatite, growth factors, and drugs. Several methods of drug delivery are being tested, including scaffold immersion and gelatins. There is also the recent development of “multifunctional” scaffolds that offer functions such as on-demand ablation of cancer cells.

1. Douglas J. Harrison, David S. Geller, Jonathan D. Gill, Valerae Lewis
2. & Richard Gorlick (2018) Current and future therapeutic approaches for osteosarcoma, Expert Review of Anticancer Therapy, 18:1, 39-50, DOI: 10.1080/14737140.2018.1413939
3. Moore DD, Luu HH. Osteosarcoma. Cancer Treat 2014;162:65-92. doi:10.1007/978-3-319-07323-1_4
4. Huang J, Xie F, Tan X, Xing W, Zheng Y, Zeng C. Treatment of Osteosarcoma of the Talus With a 3D-Printed Talar J Foot Ankle Surg. 2021;60(1):194-198. doi:10.1053/j.jfas.2020.01.012
5. Cao SS, Li SY, Geng YM, et Prefabricated 3D-Printed Tissue-Engineered Bone for Mandibular Reconstruction: A Preclinical Translational Study in Primate. ACS Biomater Sci Eng. 2021;7(12):5727-5738. doi:10.1021/acsbiomaterials.1c00509
6. Zhu C, He M, Sun D, et 3D-Printed Multifunctional Polyetheretherketone Bone Scaffold for Multimodal Treatment of Osteosarcoma and Osteomyelitis. ACS Appl Mater Interfaces. 2021;13(40):47327-47340. doi:10.1021/acsami.1c10898
7. Cai B, Huang L, Wang J, et al. 3D Printed Multifunctional Ti6Al4V-Based Hybrid Scaffold for the Management of Osteosarcoma. Bioconjug Chem. 2021;32(10):2184-2194. doi:10.1021/acs.bioconjchem.1c00367