Three-dimensional printed strontium-containing mesoporous bioactive glass scaffolds for repairing rat critical-sized calvarial defects.

The development of a new generation of biomaterials with high osteogenic ability for fast osseointegration with host bone is being intensively investigated. In this study, we have fabricated three-dimensional (3-D) strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds by a 3-D printing technique. Sr-MBG scaffolds showed uniform interconnected macropores (∼400µm), high porosity (∼70%) and enhanced compressive strength (8.67±1.74MPa). Using MBG scaffolds as a control, the biological properties of Sr-MBG scaffolds were evaluated by apatite-forming ability, adhesion, proliferation, alkaline phosphatase activity and osteogenic gene expression of osteoblast-like cells MC3T3-E1. Furthermore, Sr-MBG scaffolds were used to repair critical-sized rat calvarial defects. The results showed that Sr-MBG scaffolds possessed good apatite-forming ability and stimulated MC3T3-E1 cell proliferation and differentiation. Importantly, the in vivo results revealed that Sr-MBG scaffolds had good osteogenic capability and stimulated new blood vessel formation in critical-sized rat calvarial defects within 8 weeks. Therefore, 3-D printed Sr-MBG scaffolds with favorable pore structure and high osteogenic ability have more potential applications in bone regeneration.

Magnetic mesoporous silica nanoparticles for potential delivery of chemotherapeutic drugs and hyperthermia.

Magnetic mesoporous silica (MMS) nanoparticles with controllable magnetization have been synthesized by encapsulating Fe3O4 nanoparticles in a mesoporous silica matrix. The structure, magnetic heating capacity and drug delivery ability of MMS nanoparticles were evaluated. The results showed that MMS nanoparticles had an average particle size of 150 nm and showed low cytotoxicity and efficient cell uptake ability. MMS nanoparticles exhibited a sustained drug release in the medium of pH 5.0, but a very slow release in the medium of pH 7.4. On the other hand, MMS nanoparticles could controllably generate heat to reach the hyperthermia temperature within a short time upon exposure to an alternating magnetic field due to the superparamagnetic behavior and controllable magnetization. Therefore, MMS nanoparticles could provide a promising multifunctional platform for the combination of chemotherapy and hyperthermia for cancer therapy.

Mesoporous silica nanoparticles for enhancing the delivery efficiency of immunostimulatory DNA drugs.

We developed a potential immunostimulatory double-stranded DNA (dsDNA) delivery system by the binding of dsDNA to amino-modified mesoporous silica nanoparticles (MSNs) to form MSN-NH2/dsDNA complexes. Serum stability, in vitro cytotoxicity, cell uptake, and type I interferon-α (IFN-α) induction of MSN-NH2/dsDNA complexes were evaluated. The results showed that MSN-NH2 nanoparticles had no cytotoxicity to Raw 264.7 cells, and MSN-NH2/dsDNA complexes enhanced the serum stability of dsDNA due to the protection by nanoparticles and exhibited a high efficiency of cell uptake due to a small particle size and excellent dispersity. Most importantly, MSN-NH2/dsDNA complexes significantly enhanced the level of IFN-α induction, triggered by cytosolic DNA sensor proteins. Therefore, binding of immunostimulatory DNA to MSNs would play a promising role for enhancing the delivery efficiency of immunostimulatory DNA drugs.

Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration.

In this study, we fabricated strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds with controlled architecture and enhanced mechanical strength using a three-dimensional (3-D) printing technique. The study showed that Sr-MBG scaffolds had uniform interconnected macropores and high porosity, and their compressive strength was ∼170 times that of polyurethane foam templated MBG scaffolds. The physicochemical and biological properties of Sr-MBG scaffolds were evaluated by ion dissolution, apatite-forming ability and proliferation, alkaline phosphatase activity, osteogenic expression and extracelluar matrix mineralization of osteoblast-like cells MC3T3-E1. The results showed that Sr-MBG scaffolds exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment with increasing Sr substitution. Importantly, Sr-MBG scaffolds possessed good apatite-forming ability, and stimulated osteoblast cells' proliferation and differentiation. Using dexamethasone as a model drug, Sr-MBG scaffolds also showed a sustained drug delivery property for use in local drug delivery therapy, due to their mesoporous structure. Therefore, the 3-D printed Sr-MBG scaffolds combined the advantages of Sr-MBG such as good bone-forming bioactivity, controlled ion release and drug delivery and enhanced mechanical strength, and had potential application in bone regeneration.

Substitutions of strontium in mesoporous calcium silicate and their physicochemical and biological properties.

Calcium silicate (Ca-Si) based bioceramics have been regarded as a potential bioactive materials for bone tissue regeneration. In this study, we have successfully prepared ordered mesoporous strontium (Sr)-substituted CaSiO3 (Sr-CaSiO3) materials by using a triblock copolymer (P123) as a structure-directing agent. The microstructure and porosity of mesoporous Sr-CaSiO3 materials were investigated by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and the N2 adsorption-desorption technique. The substitution of Sr for Ca in mesoporous CaSiO3 did not change the mesoporous structure, but the surface area and pore volume decreased with increasing Sr substitution. The effects of the Sr substitution on the physiochemical and biological properties of mesoporous CaSiO3 materials were evaluated by the ion dissolution, apatite-forming ability, proliferation and alkaline phosphatase (ALP) activity of osteoblast-like MC3T3-E1 cells. The results showed that the increasing Sr substitution decreased the dissolution rate of Ca and Si ions from mesoporous CaSiO3 materials and enhanced the ability to stabilize the pH environment. Mesoporous Sr-CaSiO3 materials have a similar apatite-forming ability to mesoporous CaSiO3 material, and stimulated the proliferation and ALP activity of MC3T3-E1 cells. Furthermore, using gentamicin as a model drug, mesoporous Sr-CaSiO3 materials exhibited a sustained drug release property which could be used in local drug delivery therapy. Furthermore, the drug release rate decreased to some extent with increasing Sr substitution in mesoporous CaSiO3 materials. Therefore, mesoporous Sr-CaSiO3 materials have more potential for application in bone tissue regeneration.

Preparation and characterization of multifunctional magnetic mesoporous calcium silicate materials.

We have prepared multifunctional magnetic mesoporous Fe-CaSiO3 materials using triblock copolymer (P123) as a structure-directing agent. The effects of Fe substitution on the mesoporous structure, in vitro bioactivity, magnetic heating ability and drug delivery property of mesoporous CaSiO3 materials were investigated. Mesoporous Fe-CaSiO3 materials had similar mesoporous channels (5-6 nm) with different Fe substitution. When 5 and 10% Fe were substituted for Ca in mesoporous CaSiO3 materials, mesoporous Fe-CaSiO3 materials still showed good apatite-formation ability and had no cytotoxic effect on osteoblast-like MC3T3-E1 cells evaluated by the elution cell culture assay. On the other hand, mesoporous Fe-CaSiO3 materials could generate heat to raise the temperature of the surrounding environment in an alternating magnetic field due to their superparamagnetic property. When we use gentamicin (GS) as a model drug, mesoporous Fe-CaSiO3 materials release GS in a sustained manner. Therefore, magnetic mesoporous Fe-CaSiO3 materials would be a promising multifunctional platform with bone regeneration, local drug delivery and magnetic hyperthermia.