BackgroundBone cement plays an important role in the treatment of osteoporotic vertebral compression fractures. Calcium phosphate cement (CPC) is a potential alternative to poly(methyl methacrylate), currently the gold standard of bone cements. However, the poor mechanical properties of CPCs limit their clinical applications. The objective of this study was to develop reinforced CPCs for minimally invasive orthopedic surgeries by compositing silk fibroin (SF) with α-tricalcium phosphate.MethodsSF solution was treated with calcium hydroxide and characterized by Zeta potential analyzer and Fourier transform infrared spectroscopy. The alkaline-treated SF (tSF) was com-posited with α-tricalcium phosphate to obtain tSF/CPC composite, which was characterized using mechanical tests, scanning electron microscopy, handling property and biocompatibility tests, and sheep vertebral augmentation tests.ResultsUpon treatment with calcium hydroxide, larger SF particles and more abundant negative charge appeared in tSF solution. The tSF/CPCs exhibited a compact structure, which consisted of numerous SF -CPC clusters and needle-like hydroxyapatite (HAp) crystals. In addition, high transition rate of HAp in tSF/CPCs was achieved. As a result, the mechanical property of tSF/ CPC composite cements was enhanced remarkably, with the compressive strength reaching as high as 56.3±1.1 MPa. Moreover, the tSF/CPC cements showed good injectability, anti-washout property, and decent biocompatibility. The tSF/CPCs could be used to augment defected sheep vertebrae to restore their mechanical strength.ConclusiontSF/CPC may be a promising composite bone cement for minimally invasive orthopedic surgeries.