Curcumin and resveratrol delivery from multi-functionalized calcium phosphate scaffold enhances biological properties

Natural medicinal compounds (NMCs) can assist effectively in treating bone disorders. NMC release kinetics from a ceramic bone tissue engineering scaffold can be tailored. However, inferior physicochemical properties halt their therapeutic applications and need a carrier system for delivery. We developed a multi-functionalized scaffold to understand the effect of curcumin (Cur) and resveratrol (Rsv) on in vitro biological properties. Polycaprolactone (PCL) nanoparticles encapsulated resveratrol in the polymeric matrix. Nanoparticles showed a hydrodynamic diameter of about 180 nm, - 16 mV zeta potential, and up to ~65 % encapsulation efficiency. Scaffolds made of zinc-doped tricalcium phosphate (Zn-TCP) were coated with curcumin followed by either resveratrol (Cur-Rsv) or resveratrol nanoparticles (Cur-Rsv-NP). NMC-loaded scaffolds exhibited a biphasic release pattern over 60 days. Solubility and hydrophobic-hydrophilic interactions affected the NMC release profile. Resveratrol showed rapid release as compared to curcumin. The treated scaffold increased the cell viability of human fetal osteoblast (hFOB) by 1.8-fold as compared to the control. It exhibited a 6-fold increase in cytotoxicity toward osteosarcoma (MG-63) cells as compared to the untreated scaffold. NMCs loaded scaffold effectively inhibited Staphylococcus aureus from colonizing over the scaffold. Zinc doping enhanced osteoblast growth and prevented bacterial colony formation. Such design principle provided a direction for developing multi-functionalized calcium phosphate (CaP) scaffolds against bone diseases for orthopedic applications.