Development and evaluation of local regenerative biomimetic bone-extracellular matrix scaffold loaded with nano-formulated quercetin for orthopedic fractures.

The prevalence of bone injuries is greatly increasing each year and the proper healing of fractures without any complications is very challenging. Self-setting calcium phosphate cements (CPCs) have attracted great attention as bioactive synthetic bone substitutes. Quercetin (QT) is a multipurposed drug with reported bone-conserving properties. The loading of QT and QT-phospholipid complex within nanostructured lipid carriers (NLC) was proposed to overcome the poor physical properties of the drug and to introduce the use of bioactive excipients as phospholipids and olive oil. The aim of this work was to formulate a regenerative scaffold loaded with nano-formulated QT for local treatment of orthopedic fractures. For the first time, scaffolds composed of brushite CPC were prepared and loaded with quercetin lipid nano-systems. In vitro tests proved that the addition of lipid nano-systems did not deteriorate the properties of CPC where QT-NLC/CPC showed an adequate setting time, appropriate compressive strength, and porosity. The scanning electron microscope confirmed maintenance of nanoparticles integrity within the cement. Using a rat femur bone defect animal model, the histological results showed that the QT-NLC/CPC had a superior bone healing potential compared to crude unformulated QT/CPC. In conclusion, QT-NLC /CPC are promising lipid nano-composite materials that could enhance bone regeneration.