As bone defects are usually difficult to repair by themselves, and usually require bone transplantation to repair, excellent bone graft materials are an important means of clinical repair of bone defects[1].
Although autogenous bone has high osteogenic activity, patients need a second operation, resulting in more blood loss and more trauma [2]. While allogeneic bone has risks of disease transmission, immune rejection and post-implantation reabsorption[3]. In addition the sources of autogenous bone and allogeneic bone are limited.
Bone repair materials have the advantages of extensive sources, controllable operating conditions and no immunogenicity, and the clinical demand for them is increasing .Metal materials, polymer materials, bioceramics and composites are all candidates for research and preparation of artificial bone substitutes.Metal materials are the most widely used orthopedic plants, with sufficient corrosion resistance, mechanical property and processability.The main problem of metal materials is that the corrosion of the physiological environment will change the physical and chemical properties of the materials, making the grafts loose and damaged. The increase of ion level will have potential toxic and side effects on the body[4]. Natural macromolecules used for artificial bone include collagen, fibrin, silk fibroin, alginate and chitosan. Collagen and chitosan have the advantages of good biocompatibility, biodegradability, promoting cell adhesion and growth, and convenient material collection.However, its mechanical strength is insufficient, its degradation rate is too fast, its biological property is unstable, its manufacturing capacity is limited, it can not withstand greater pressure and it is difficult to obtain, so it is not suitable to be used as a matrix material for bone defect repair alone[5].Bioceramic materials are widely used in the medical industry due to their similar density and composition to human bone, stable chemical properties, high mechanical strength, corrosion resistance, good biocompatibility and other advantages[6].In recent years, the combination of electrospinning technology, nanotechnology, hydrogel technology, 3D printing and other technologies with bioceramics has greatly strengthened the application scope of its bone tissue engineering technology.
As an essential trace element of bone formation,zink(Zn), most found in the bones,is a component of many metalloenzymes ,as well as an activator of enzymes. During the maturation of osteoblasts, Zn2+ can form an alkaline microenvironment, which is conducive to the deposition and mineralization of phosphates outside osteoblasts[7].Inorganic phosphorus can affect bone growth, collagen growth rate and bone matrix mineralization, and regulate calcium in bone matrix[8]. Phosphate bioceramics have good biocompatibility, bone conductivity, and biological activity, making them widely used in dental implants, bone filling, bone transplantation, spinal fusion, drug delivery systems and other fields [9].Zinc phosphate ceramic is widely used in the field of bone tissue engineering because of their good biocompatibility and certain osteogenic properties[10, 11].However, due to the potential biological toxicity of high concentration zinc and insufficient osteogenic properties, Zinc phosphate ceramic is hardly to become an ideal bone repair material.
Although strontium (Sr) is a non-essential trace element in human body. Sr2+ is considered to replace ca2+ in the process mediated by osteoblasts, and finally deposited in the mineralized structure of bone[12]. Its existence is considered to have the effect of preventing caries and enhancing bone strength, and may have a dual effect of stimulating bone formation, that is, stimulating osteoblast osteogenesis and inhibiting osteoclast bone absorption behavior,Meanwhile, strontium can activate the second messenger and cell mitogen-activated proteins Kinase signaling pathway, and can inhibit the interaction between RANKL-RANK[13].Strontium ranelate have been widely used in the treatment of osteoporosis in postmenopausal women[14].A large number of studies have shown that the incorporation of Sr into biomaterials can effectively enhanced osteogenesis and inhibited osteoclast in vitro[15–17]. Since Strontium has multiple functions that affect bone physiology, it can be used as a promising biomaterial for human bone repair and regeneration. Many studies have shown that strontium doped magnesium ceramics can significantly improve osteogenesis, and strontium and magnesium play a synergistic role in this process at a relatively low concentration.We doped strontium into zinc phosphate ceramics to explore the osteogenesis mechanism under the coexistence of zinc and strontium, hoping to improve the osteogenesis efficiency and reduce the toxicity of single metal element.
Inorganic nanomaterials have broad application prospects due to their advantages of easy processing, good mechanical properties, and maintaining stability for several weeks in vivo.Nanomaterials have been widely used in directing stem cell differentiation.A lot of studies show that gold nanoparticles and hydroxyapatite nanoparticles can promote the osteogenic differentiation of stem cells[18, 19].
In this study, we synthesized Zn2Sr(PO4)2 nanoparticles through high temperature solid state method .In vitro, the effects of different concentrations of nanoparticles leach liquor on the proliferation and differentiation of MC3T3-E1 cells was tested .In vivo, we verified the effect of Zn2Sr(PO4)2 nanoparticles repairing the bone defect of the lateral epicondyle of femur in rats.