No abstract

Inorganic bioactive nanomaterials are attractive for hard tissue regeneration, including nanocomponents for bone replacement composites and nanovehicles for delivering therapeutics. Bioactive glass nanoparticles (BGn) have recently gained potential usefulness as bone and tooth regeneratives. Here we demonstrate the capacity of the BGn with mesopores to load and deliver therapeutic molecules (drugs and particularly genes). Spherical BGn with sizes of 80-90 nm were produced to obtain 3-5 nm sized mesopores through a sono-reacted sol-gel process. A simulated body fluid test of the mesoporous BGn confirmed their excellent apatite forming ability and the cellular toxicity study demonstrated their good cell viability up to 100 μg ml(-1). Small molecules like chemical drug (Na-ampicillin) and gene (small interfering RNA; siRNA) were introduced as model drugs considering the mesopore size of the nanoparticles. Moreover, amine-functionalization allowed switchable surface charge property of the BGn (from -20-30 mV to +20-30 mV). Loading of ampicillin or siRNA saturated within a few hours (~2 h) and reflected the mesopore structure. While the ampicillin released relatively rapidly (~12 h), the siRNA continued to release up to 3 days with almost zero-order kinetics. The siRNA-nanoparticles were easily taken up by the cells, with a transfection efficiency as high as ~80%. The silencing effect of siRNA delivered from the BGn, as examined by using bcl-2 model gene, showed dramatic down-regulation (~15% of control), suggesting the potential use of BGn as a new class of nanovehicles for genes. This, in conjunction with other attractive properties, including size- and mesopore-related high surface area and pore volume, tunable surface chemistry, apatite-forming ability, good cell viability and the possible ion-related stimulatory effects, will potentiate the usefulness of the BGn in hard tissue regeneration.

Designing scaffolds with bioactive composition and long-term drug delivery capacity is a promising method to improve the therapeutic efficacy in bone regeneration. Herein, electrospun fibrous scaffolds of polycaprolactone-gelatin incorporating mesoporous bioactive glass nanoparticles (mBGn) were proposed to be excellent matrix platforms for bone tissue engineering. In particular, the mBGn were loaded with osteogenic drug Dexamethasone (DEX) to elicit additional therapeutic potential. The mBGn-added fiber scaffolds demonstrated excellent properties, including improved mechanical tensile strength, elasticity, and hydrophilicity compared to pure biopolymer matrix. The scaffolds could release substantial amounts of calcium and silicate ions. The loading of DEX onto mBGn was as high as 63%, that is, 0.63 mg DEX loaded per 1 mg of mBGn, demonstrating an effective nanodepot role of the mBGn. The release of DEX from the mBGn-added fiber scaffolds was highly sustainable, profiling an almost linear release kinetics up to the test period of 28 days, after a rapid initial release of ∼30% within 24 h. The proliferation and osteogenic differentiation of stem cells derived from periodontal ligament were significantly improved by the mBGn incorporation and synergistically stimulated with DEX loading, as confirmed by both direct and indirect cultures. The effects on bone regeneration in vivo, as analyzed by microcomputed tomography and histological stains in a rat calvarium model over 6 weeks, were substantial with the mBGn incorporation and even better with DEX loading, evidencing the osteogenic effects of the drug-eluting nanocomposite fiber scaffolds in bone formation. The current scaffolds with bone-bioactive composition and drug delivery capacity may be potentially useful for bone regeneration as novel osteogenic matrices.