Study on injectable silver-incorporated calcium phosphate composite with enhanced antibacterial and biomechanical properties for fighting bone cement-associated infections.

Although commonly used in orthopedic surgery, bone cements often face a high risk of post-operative infection. Developing bone cement with antibacterial capability is an effective path for eliminating implant-associated infections. Herein, the potential of silver ions (Ag+) and silver nanoparticles (AgNPs) in modifying CPC for long-term antibacterial property was investigated. Ag+ ions or AgNPs of various concentrations were incorporated in starch-modified calcium phosphate bone cement (CPB) to obtain Ag+-containing (Ag+@CPB) and AgNPs-containing (AgNP@CPB) bone cements. The results showed that all silver-containing CPBs had setting times of about 25-40 min, compressive strengths of greater than 22 MPa, high cytocompatibility but inhibitory effect on Staphylococcus aureus growth. After soaking for 1 week, the mechanical properties and the cytocompatibility of all cements revealed no significant changes, but only CPB with a relatively high content of Ag+ (H-Ag+@CPB) maintained good antibacterial capability over the tested time period. In addition, all the cements showed high injectability and interdigitating capability in cancellous bone and demonstrated augmentation effect on the cannulated pedicle screws fixation in the Sawbones model. In summary, the sustainable antibacterial capability and enhanced biomechanical properties demonstrated that Ag+ ions were more suitable for the fabrication of antibacterial CPC compared to AgNPs. Also, the H-Ag+@CPB, with good injectability, high cytocompatibility, good interdigitating and biomechanical property in cancellous bone, and sustainable antibacterial effects, bears great potential for the treatments of bone infections or implant-associated infections.

Strontium-calcium phosphate hybrid cement with enhanced osteogenic and angiogenic properties for vascularised bone regeneration.

Vascularized bone tissue engineering is regarded as one of the optimal treatment options for large bone defects. The lack of angiogenic properties and unsatisfactory physicochemical performance restricts calcium phosphate cement (CPC) from application in vascularized bone tissue engineering. Our previous studies have developed a starch and BaSO4 incorporated calcium phosphate hybrid cement (CPHC) with improved mechanical strength and handling properties. However, the bioactivity-especially the angiogenic ability-is still absent and requires further improvement. Herein, based on the reported CPHC and the osteogenic and angiogenic properties of strontium (Sr) ions, a strontium-enhanced calcium phosphate hybrid cement (Sr-CPHC) was developed to improve both biological and physicochemical properties of CPC. Compared to CPC, the initial setting time of Sr-CPHC was prolonged from 2.2 min to 20.7 min. The compressive strength of Sr-CPHC improved from 11.21 MPa to 45.52 MPa compared with CPC as well. Sr-CPHC was biocompatible and showed promotion of alkaline phosphatase (ALP) activity, calcium nodule formation and osteogenic relative gene expression, suggesting high osteogenic-inductivity. Sr-CPHC also facilitated the migration and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and up-regulated the expression of the vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1). In vivo evaluation showed marked new bone formation in a rat calvarial defect model with Sr-CPHC implanted. Sr-CPHC also exhibited enhancement of neovascularization in subcutaneous connective tissue in a rat subcutaneous implantation model. Thus, the Sr-CPHC with the dual effects of osteogenesis and angiogenesis shows great potential for clinical applications such as the repair of ischemic osteonecrosis and critical-size bone defects.