Multiple Drug Delivery Ability of Calcium Phosphate Scaffolds promotes Osteogenic Gene Expression in In Vitro...

This study investigates the incorporation of curcumin, resveratrol, and vitamin D3 into polymer-integrated calcium phosphate (CaP) scaffolds to assess their effects on osteogenic gene expression and osteosarcoma cell viability. Polymeric micelles and a polycaprolactone-polyethylene glycol (PCL-PEG) system were utilized to enhance drug loading, release, and bioactivity.

The scaffolds were functionalized with curcumin, resveratrol, and vitamin D3 using different polymeric carriers for controlled release. The release profile of these drugs was evaluated at physiological and acidic pH conditions. Osteoblast proliferation and differentiation were assessed. An osteoblast and osteoclast co-culture and RT-qPCR were performed to investigate osteogenic and osteoclastic gene expression. Resorption pit formation and Tartrate-Resistant Acid Phosphatase (TRAP) assays were conducted to analyze osteoclast activity. Lastly, osteosarcoma cell viability and morphology were examined at multiple time points to determine the anti-osteosarcoma efficacy of the drugs in vitro.

The drug release study shows sustained release over a period of three days. At pH 5.0, the cumulative release of curcumin, resveratrol, and vitamin D3 reached 64%, 100%, and 80%, respectively. At pH 7.4, the corresponding release values were 25% for curcumin, 69% for vitamin D3, and 92% for resveratrol. In vitro, treated scaffolds enhance osteoblast proliferation by 1.1to 1.3-fold and upregulate key osteogenic markers. Osteoclast activity was significantly reduced, with smaller resorption pits and decreased TRAP activity. Osteosarcoma viability decreases by 2.5to 2.8-fold by day 11, indicating anti-cancer efficacy of the drugs.

The scaffolds successfully delivered bioactive compounds that promote osteoblast growth while reducing osteoclast activity and osteosarcoma cell proliferation. This multifunctional approach demonstrates the potential for enhancing bone regeneration and minimizing tumor recurrence post-surgery.