3D Printed Calcium Phosphate Cement (CPC) Scaffolds for Anti-Cancer Drug Delivery

Abstract

One of the main applications of bone graft materials is filling the gap after the surgical removal of bone cancer or tumors. Insufficient healing commonly leads to non-union fracture which could lead to cancer resurgence or infection. Emerging 3D printing of on-demand bone graft biomaterials can deliver personalized solutions with minimized risk of relapse and recurrence of cancer after bone removal surgery. This research aims to explore 3D printed calcium phosphate cement (CPC) based scaffolds as novel anti-cancer drug delivery systems to treat bone cancer. For the study, various 3D printed CPC based scaffolds (diameter 5 mm) with interconnected pores were utilized. Various optimized polymeric solutions containing a model anticancer drug 5-fluorouracil (5-FU) was used to homogenously coat the CPC scaffolds. Both hydrophilic Soluplus (SOL) and polyethylene glycol (PEG) and a combination of both were used to develop stable coating solutions. The surface morphology of the coated scaffolds, observed via SEM, revealed deposition of the polymeric solution represented by a semi-smooth surface as opposed to the blank scaffolds that showed a smoother surface. An advanced surface analysis conducted via confocal microscopy showed a homogenous distribution of the drug throughout the coated scaffolds. Solid-state analysis studied by applying differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed semi-crystalline nature of the drug whereas mechanical analysis conducted via texture analysis showed no evidence in the change of the mechanical properties of the scaffolds after polymeric solutions were applied. The FTIR analysis revealed no major intermolecular interactions between 5-FU and the polymers used for coatings except for F2 where a potential nominal interaction was evidenced corresponding to higher Soluplus content in the formulation. In vitro dissolution studies showed that almost 100% of the drug released within 2 h for all scaffolds. Moreover, in vitro cell culture using two different cell lines (Hek293T-human kidney immortalized cell line and HeLa-human bone osteosarcoma epithelial cell line) showed significant inhibition of cell growth as a function of decreased numbers of cells after 5 days. It can be claimed that the developed 5-FU coated 3D printed scaffolds can successfully be used as bone graft materials to potentially treat bone cancer or bone neoplasm and for personalized medical solutions in the form of scaffolds for regenerative medicine or tissue engineering applications.

Bioinspired Modifications of PEEK Implants for Bone Tissue Engineering

“…In order to reduce the risk of tumor recurrence after a bone removal surgery, applying an implant with anti-cancer agents is an effective method. Studies confirmed that the anti-cancer drugs (e.g., methotrexate, and 5fluorouracil) loaded in ceramic cements could inhibit the growth of osteosarcoma cell line (Prasad et al, 2018;Wu et al, 2020). Currently, light-assisted photothermal therapy (PTT) based on photothermal conversion agent (e.g., MXenes) was introduced to PEEK implants to defect osteosarcoma cells (Yin et al, 2020).…”

Bone Tissue Engineering through 3D Bioprinting of Bioceramic Scaffolds: A Review and Update

“…These include hydroxyapatite, calcium phosphate, calcium sulfate, and bioactive glasses and are the most common and clinically available bone substitute materials. Hence, bioceramic scaffolds represent a cornerstone for bone regeneration, as they have distinct properties that emerge as promising alternatives to bone grafts [ 62 , 63 , 64 , 65 ].…”

Three-Dimensional (3D) Printing in Cancer Therapy and Diagnostics: Current Status and Future Perspectives

“…The in vitro data showed that the cell growth of the Hek293T-human kidney immortalized cell line and HeLa-human bone osteosarcoma epithelial cell line were decreased after 5 days. The study suggested that it could be successfully used to treat bone cancer and as a personalized medical solution for tissue engineering applications [156]. Three-dimensional-printed nanogel disc rounds act as drug carriers in delivering paclitaxel and rapamycin via intraperitoneal administration in ES-2-luc ovarian-cancer-bearing xenograft mice and are reported to be therapeutically effective in preventing postsurgical peritoneal adhesion in cancer-bearing mice [157].…”