Multifunctional gelatin–tricalcium phosphate porous nanocomposite scaffolds for tissue engineering and local drug delivery: In vitro and in vivo studies

Abstract Bone is known as the most prevalent, metastatic site of breast cancer; however, it's mechanism details are unknown, so developing a suitable scaffold for bone defect regeneration and sustain drug release after tumor resection can considerably inhibit the tumor recurrence after a while. Here, synthesized gelatin/beta-tricalcium phosphate (β-TCP) nanocomposite scaffold loaded with zoledronic acid (ZA) drug with different β-TCP concentrations, crosslinker and varying drug doses were investigated to highlight their effect on biological properties of the scaffold contained bone cells. The scanning electron microscopy (SEM) illustrated porous structure (50–200 µm) of gelatin reinforced with β-TCP spherical nanoparticles (around 90 nm diameter) that could be a proper matrix for bone cells proliferation. In vitro biological analysis by cytotoxicity assay (MTT test) as well as osteoblast cell line (G292) attachment test showed that the scaffolds were biocompatible and non-toxic. Also, higher β-TCP nanoparticle concentration enhanced the rate of cell proliferation on the scaffold. Further investigations indicated that the type of cell seeding into porous scaffolds should be considered as a significant parameter in cell behavior on the scaffold. The better cell attachment was observed in agarose gel wells in comparison with the petri dish one. Nanocomposite samples were loaded with ZA drug and its effects on the cell proliferation were investigated in vitro and in vivo as well. Histopathological results showed that the new bone formation was established more than 75% in the whole area of the defect after 3 and 4 months. For the first time, nanoscaled β-TCP/gelatin composite was proposed as a potential for controlled drug release and local resected tumor treatment. All findings besides in vitro and in vivo analyses, recommend gelatin/nano beta-tricalcium phosphate/drug scaffolds as a promising three-dimensional environment for repairing the resected bone tissue in primary or metastatic bone sites.