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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.

Organic coatings have been proposed as a solution to foster osseointegration of orthopedic implants. Among them, extracellular matrix-derived peptide motifs are an interesting biomimetic strategy to harness cell-surface interactions. Nonetheless, the combination of multiple peptide motifs in a controlled manner is essential to achieve receptor specificity and fully exploit the potentiality of synthetic peptides. Herein, we covalently graft to titanium a double branched molecule to guide stem cell fate in vitro and generate an osseoinductive titanium surface in vivo. Such synthetic ligand allows for the simultaneous presentation of two bioactive motifs, thus is ideal to test the effect of synergic sequences, such as RGD and PHSRN, and is a clear example of the versatility and feasibility of rationally designed biomolecules.

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