3D printed core/shell scaffold based on nano/microspheric hydrogel for osteosarcoma anticancer delivery and bone regeneration

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Abstract
One of the most common types of bone cancer is osteosarcoma. Currently a combination of therapies including surgery, chemotherapy, and radiation therapy is used. Bone defects, re-formation of the tumor, or remaining tumor cells after the surgery are the main challenges of osteosarcoma treatments. Scaffolds can be used to overcome the bone defects problem. In this study, we aim to fabricate a bilayer scaffold with the capacity of avoiding tumor recurrence and stimulating bone regeneration which brings a novel idea for osteosarcoma treatments. First, methotrexate was encapsulated in PLGA microspheres with 13.5% loading capacity. Then, coaxial extrusion-based 3D printer via a customized bilayer core-shell nozzle was employed to fabricate the scaffold. The implanted scaffold was printed by using gelatin methacrylol (GelMA) hydrogel containing methotrexate microspheres in the outer layer for anticancer drug delivery, and GelMA/alginate hydrogel containing nanohydroxyapatite and nanosilica in the inner layer for bone regeneration. The outer layer of the scaffold had rapidly degraded within 20 days and it played a great role in drug delivery and inhibiting the tumor cells’ growth. The inner layer with 4% nanosilica had slow degradation rate at about 50% in 60 days and it showed the highest mechanical strength with 225 kPa. Regarding osteogenesis property, ALP enzyme activity was increased considerably within 3 weeks. Also, significant increase in osteogenesis markers of RUNX2, OPN, and COL1A1 was observed. In addition to drug delivery at the tumor site, this bilayer scaffold could be a platform for the placement of healthy bone cells after drug delivery.

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