Osteoinductive Fibrous Scaffolds of Biopolymer/Mesoporous Bioactive Glass Nanocarriers with Excellent Bioactivity and Long-Term Delivery of Osteogenic Drug

Abstract

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.

Inhibition of osteoclastogenesis through siRNA delivery with tunable mesoporous bioactive nanocarriers

“…We consider that there are some beneficial effects of the bioactivity and degradability of MBG on cell viability. Previously the nanoparticulate form of bioactive glasses produced by a sol-gel process was shown to have excellent bone-bioactivity by forming apatite nanocrystallites in a simulated body fluid in vitro, furthermore, the nanoparticles released Ca and Si ions over 4 weeks, revealing a degree of degradability [73,74]. In fact, the ionic release, including Si and Ca, from the conventional BGs has already proven stimulatory effects on the proliferation of osteoblasts and precursor/stem cells [57,62].…”

Bioactive glass-based nanocomposites for personalized dental tissue regeneration

“…According to the revealed results, cytotoxicity could be dependent on the cell type and the ratio of cell number to nanoparticle concentration. Toxicity of BGNs in dental tissue-derived cells such as dental pulp stem cells, odontoblasts, periodontal ligament cells, cementoblasts and gingival fibroblasts was not detected in the low concentration (≤100 μg/mL) and the in vivo study [99][100][101][102] including several clinical cases 5,13,69,74) . However, further detailed researches of BGNs including the long-term study are needed for their safe use 9,13,14) .…”

“…Therefore, various BGNs have been fabricated with bioceramic cement and synthetic polymers for osteogenic or odontogenic properties [12][13][14]72,73) . Owing to mesoporosity of BGNs, therapeutic drugs could be loaded and accelerate biological effects of these nanocompositebased BGNs 49,[74][75][76][77] . Use of BGNs for treatment of hypersensitivity in the tooth restoration has led to a form of very fine Bioglass ® particulates called NovaMin ® (NovaMin Technology, GlaxoSmithKline, London, UK) and sol-gel derived BGNs as an active repair additive in toothpaste.…”

Delivery of dexamethasone from bioactive nanofiber matrices stimulates odontogenesis of human dental pulp cells through integrin/BMP/mTOR signaling pathways

“…15 Moreover, the proliferation and osteogenic differentiation of stem cells derived from periodontal ligament were stimulated by the long-term delivery of DEX that was incorporated within composite nanofibers. 16 Based on these series of studies, we proposed to utilize the DEX delivery system made of nano-biomatrices that have nanofibrous morphology and bioactive nanocomponent within the composition, targeting odontogenic differentiation of dental stem cells. We cultured dental stem cells derived from human pulp (HDPCs) upon the DEX-delivering nanobiomatrices and investigated the odontogenesis of cells; moreover, we addressed the biological signaling pathways behind these events.…”

“…First, the nanocomponent (BGN) added within the nanofiber matrix was prepared by the sol-gel approach. 16,17 In brief, 5 g polyethylene glycol (PEG) was dissolved in 120 mL methanol with pH adjusted to 12.5, and then 0.299 g Ca (NO 3 ) 2 ⋅4H 2 O was added and dissolved. Separately, 0.793 g TEOS (tetraethyl orthosilicate) was added to 30 mL methanol, which was then added dropwise to the pH-adjusted solution with ultrasonication.…”