Strontium-incorporated mesoporous bioactive glass scaffolds stimulatingin vitroproliferation and differentiation of bone marrow stromal cells andin vivoregeneration of osteoporotic bone defects

Abstract

Osteoporosis is one of the most widely occurring bone disorders characterized by low bone mineral density and poor bone strength. Strontium ranelate, as a treatment option, has received significant attention in recent years due to its ability to halt the progress of osteoporosis by simultaneously improving bone formation and reducing bone resorption. Although much emphasis has been given to the treatment of osteoporosis and fracture prevention using pharmacological agents, much less attention has been placed on the repair of critical-sized bone fractures caused by osteoporosis. The aim of the present study was to prepare strontium-incorporated mesoporous bioactive glass (Sr-MBG) scaffolds in order to combine the therapeutic effects of Sr 2+ ions on osteoporosis with the bioactivity of MBG to regenerate osteoporotic-related fractures. Prior to animal implantation, the effects of Sr-containing ionic products from Sr-MBG scaffolds on the proliferation and differentiation of bone marrow stromal cells (BMSCs) from osteoporotic bone were investigated in an in vitro culture system. The results showed that Sr-MBG scaffolds significantly increased the proliferation of BMSCs in a concentration dependent manner and were able to stimulate the expression of osteoblast differentiation markers including Alpl, Col1a1, Runx2 and Bglap as assessed by real-time PCR. Critical sized femur defects in ovariectomised rats were created to simulate an osteoporotic phenotype. At time points 2, 4 and 8 weeks post-implantation, the in vivo osteogenetic efficiency was systematically evaluated by mCT analysis, hematoxylin and eosin staining, and immunohistochemistry (type I collagen). The results showed that the incorporation of Sr into MBG scaffolds significantly stimulated new bone formation in osteoporotic bone defects when compared to MBG scaffolds alone. Furthermore, it was generally found that Sr release in blood was maintained at a very low level and the Sr, Si, Ca and P excretion by urine operated in an a similar manner to blank control animals. Our results suggested that Sr-MBG scaffolds could be a promising biomaterial for regenerating osteoporosis-related fractures by the release of Sr-containing ionic products. Fig. 5 The 3D microarchitectural parameters analyzed by m-CT. Data are presented as mean AE SD and analyzed by one-way ANOVA and SNK tests.Fig. 6 Representative sections of HE staining demonstrate the healing defects filled with MBG, 2.5% Sr-MBG and 5% Sr-MBG. The box on the right top gives magnification of local details. Arrows: new generated bone, stars: filled scaffold, scale bar: 200 mm.

Bioactive glass-based materials with hierarchical porosity for medical applications: Review of recent advances

“…the leading teams of Vallet-Regi (Spain) and Wu and Chang (China)) extensively and systematically applied the polyurethane foam method to process a variety of MBG formulations doped with additional cations that, once released, can elicit targeted therapeutic effects [62][63][64][65][66][67][68][69][70][71][72]; an overview of these studies (along with other relevant ones) is reported in Table 2.…”

PNIPAAM modified mesoporous hydroxyapatite for sustained osteogenic drug release and promoting cell attachment

“…Every 10 mg of MHA or MHA-SIM-PNIPAAM was dipped in 40 mL fresh α-MEM with 10% FBS and 1% P/S at 37 °C for 24 h. After transient centrifugation at 1000 rpm for 1 min and then filtration by 10 mL syringe with a 0.22 μm bacterial filter, the supernatant liquid was collected. Subsequently, two kinds of extracts and a blank control were used for the following cell culture [1]. …”

“…In the past few decades, much efforts have been made to improve the feature of the bone substitutes, such as plugging in osteogenic elements [1], adjusting the pore volume or size [2], and encapsulating osteogenic drug [3]. For bone substitute, the added osteogenic drug in materials greatly contributes to the treatment of bone defects.…”

Development of mesoporous bioactive glass nanoparticles and its use in bone tissue engineering

“…Bivalent ions, such as strontium, zinc, and magnesium, were also used to substitute the MBG composition. These variants also demonstrated the stimulation of osteogenic differentiation on BMSCs . More recently, strontium has garnered interests for its reportedly promising effects on bone healing.…”