3D printed tricalcium phosphate bone tissue engineering scaffolds: effect of SrO and MgO doping on in vivo osteogenesis in a rat distal femoral defect model

Solaiman Tarafder, Neal M. Davies, Amit Bandyopadhyay, Susmita Bose
2013 Biomaterials Science  
The presence of interconnected macro pores is important in tissue engineering scaffolds for guided tissue regeneration. This study reports in vivo biological performance of interconnected macro porous tricalcium phosphate (TCP) scaffolds due to the addition of SrO and MgO as dopants in TCP. We have used direct three dimensional printing (3DP) technology for scaffold fabrication followed by microwave sintering. Mechanical strength was evaluated by scaffolds with 500 µm, 750 µm, and 1000 µm
more » ... onnected designed pore sizes. Maximum compressive strength of 12.01 ± 1.56 MPa was achieved for 500 µm interconnected designed pore size Sr-Mg doped scaffold. In vivo biological performance of the microwave sintered pure TCP and Sr-Mg doped TCP scaffolds was assessed by implanting 350 µm designed interconnected macro porous scaffolds in rat distal femoral defect. Sintered pore size of these 3D printed scaffolds were 311 ± 5.9 µm and 245 ± 7.5 µm for pure and SrO-MgO doped TCP scaffolds, respectively. These 3D printed scaffolds possessed multiscale porosity, i.e., 3D interconnected designed macro pores along with intrinsic micro pores. Histomorphology and histomorphometric analysis revealed a significant increase in osteoid like new bone formation, and accelerated mineralization inside SrO and MgO doped 3D printed TCP scaffolds as compared to pure TCP scaffolds. An increase in osteocalcin and type I collagen level was also observed in rat blood serum with SrO and MgO doped TCP scaffolds compared to pure TCP scaffolds. Our results show that these 3D printed SrO and MgO doped TCP scaffolds with multiscale porosity contributed to early healing through accelerated osteogenesis. Manuscript biocompatibility, bioactivity and non-immunogenicity of calcium phosphate (CaP) bioceramics are the primary reasons for their broad range of applications in hard tissue repair, regeneration and augmentation. 7-11 CaP bioceramics also eliminates the necessity for second surgery required for autograft harvesting. Among other CaPs, the resorbable property of β-tricalcium phosphate (β-TCP) makes it an excellent candidate to be applicable as a biodegradable bone substitute for different orthopedic and dental applications. 8, 12, 13 Biodegradable bone substitutes are eventually replaced by newly formed bone. Many trace elements such as Na + , Mg 2+ , Zn 2+ , Si 4+ , and Sr 2+ are also present in the mineral phase of natural bone. 12-14 In many cases, cation substitution in CaPs has been proven to improve mechanical properties and both in vitro and in vivo biological responses substantially. These changes in mechanical properties and biological responses are due to the changes in the physicochemical properties of CaPs such as crystallinity, microstucture and solubility caused by cation substitution. Our earlier work demonstrated that a β-TCP with desired mechanical properties can be obtained with appropriate dopants such as CaO, NaF, Ag 2 O, TiO 2 , MgO, SrO, SiO 2 , ZnO, and WO 3 at the optimum concentration without affecting the inherent biocompatibility of β-TCP. 13, 15-18 Strontium (Sr 2+ ), a trace element, which is about 0.035% of its calcium content in our skeleton system, has been shown to enhance bone regeneration when incorporated into synthetic bone graft. 19 Bone regeneration by strontium is caused by its simultaneous stimulatory effect on osteoblast mediated bone formation, and inhibitory effect on osteoclast mediated bone resorption. Due to this tremendous impact of strontium on bone modeling and remodeling and its bone seeking property, strontium has also been used in osteoporotic drug as strontium ranelate. In recent years, magnesium based CaPs and alloys have brought noticeable attention from the scientific community in bone tissue engineering due to its enormous role in human physiology such as structure stabilization of many proteins, nucleic acids, acting as a cofactor in hundreds of enzymatic reactions, signal transduction modulation and cell proliferation. 20 The effect of Mg 2+ on bone and mineral metabolism was also demonstrated by low dietary Mg 2+ intake. 21
doi:10.1039/c3bm60132c pmid:24729867 pmcid:PMC3979641 fatcat:ymo22m6kifdulgkmxya5xrsf24