Abstract
The aim of this study was to evaluate the in vitro and in vivo biocompatibility of artificial bone based on vancomycin loaded mesoporous silica nanoparticles and calcium sulfate composites. In vitro cytotoxicity tests by cholecystokinin octapeptide (CCK-8) assay showed that the 5 %Van-MSN-CaSO4 and Van-CaSO4 bone cements were cytocompatible for mouse osteoblastic cell line MC3T3-E1. The microscopic observation confirmed that MC3T3-E1cells incubated with Van-CaSO4 group and 5 %Van-MSN-CaSO4 group exhibited clear spindle-shaped changes, volume increase and maturation, showing that these cements supported adhesion of osteoblastic cells on their surfaces. In addition, the measurement of alkaline phosphatase activity revealed the osteoconductive property of these biomaterials. In order to assess in vivo biocompatibility, synthesized cements were implanted into the distal femur of twelve adult male and female New Zealand rabbits. After implantation in artificial defects of the distal femur, 5 %Van-MSN-CaSO4 and Van-CaSO4 bone cements did not damage the function of main organs of rabbits. In addition, the Van-MSN-CaSO4 composite allowed complete repair of bone defects with new bone formation 3 months after implantation. These results show potential application of Van-MSN-CaSO4 composites as bone graft materials for the treatment of open fracture in human due to its mechanical, osteoconductive and potential sustained drug release characteristics and the absence of adverse effects on the body.
Highlights
Bone transplants are broadly used in the treatment of open fractures, especially for providing mechanical or structural support and promoting the bone tissue formation [1, 2]
We used calcium sulfate particles impregnated with vancomycin for the treatment of infected bone defects of 28 cases of open fractures among which 26 cases were followed up, and found that this material is beneficial for osteoblasts migration and vascular ingrowth
Bone cement based on vancomycin loaded mesoporous silica nanoparticles (MSNs) and calcium sulfate composites (5 %Van-MSN-CaSO4) [11] and calcium sulfate impregnated with vancomycin (VanCaSO4) bone implant [12] were prepared as described elsewhere [11, 12]
Summary
Bone transplants are broadly used in the treatment of open fractures, especially for providing mechanical or structural support and promoting the bone tissue formation [1, 2]. The synthetic bone material must be safe and suitable for implantation in vivo. Calcium sulfate has got a long clinical history as bone biomaterial because apart from providing structural support, it holds good biocompatibility, osteoinductivity and bioabsorbability and can serve as a vehicle for delivery and local release of antibiotics [4,5,6,7,8]. Et al (2001) successfully used surgical grade calcium sulfate pellets as convenient and safe bone graft substitute for the treatment of patients with bone defects [9]. Additional studies on bone graft substitutes have confirmed the biocompatibility of calcium sulfate composites and suggested their use as suitable bone implant material for in vivo therapies [10, 11]. We used calcium sulfate particles impregnated with vancomycin for the treatment of infected bone defects of 28 cases of open fractures among which 26 cases were followed up, and found that this material is beneficial for osteoblasts migration and vascular ingrowth
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