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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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Three-dimensional matrices that encapsulate and deliver stem cells with defect-tuned formulations are promising for bone tissue engineering. In this study, we designed a novel stem cell delivery system composed of collagen and alginate as the core and shell, respectively. Mesenchymal stem cells (MSCs) were loaded into the collagen solution and then deposited directly into a fibrous structure while simultaneously sheathing with alginate using a newly designed core-shell nozzle. Alginate encapsulation was achieved by the crosslinking within an adjusted calcium-containing solution that effectively preserved the continuous fibrous structure of the inner cell-collagen part. The constructed hydrogel carriers showed a continuous fiber with a diameter of *700-1000 mm for the core and 200-500 mm for the shell area, which was largely dependent on the alginate concentration (2%-5%) as well as the injection rate (20-80 mL/h). The water uptake capacity of the core-shell carriers was as high as 98%, which could act as a pore channel to supply nutrients and oxygen to the cells. Degradation of the scaffolds showed a weight loss of *22% at 7 days and *43% at 14 days, suggesting a possible role as a degradable tissue-engineered construct. The MSCs encapsulated within the collagen core showed excellent viability, exhibiting significant cellular proliferation up to 21 days with levels comparable to those observed in the pure collagen gel matrix used as a control. A live/dead cell assay also confirmed similar percentages of live cells within the core-shell carrier compared to those in the pure collagen gel, suggesting the carrier was cell compatible and was effective for maintaining a cell population. Cells allowed to differentiate under osteogenic conditions expressed high levels of bone-related genes, including osteocalcin, bone sialoprotein, and osteopontin. Further, when the core-shell fibrous carriers were implanted in a rat calvarium defect, the bone healing was significantly improved when the MSCs were encapsulated, and even more so after an osteogenic induction of MSCs before implantation. Based on these results, the newly designed core-shell collagen-alginate fibrous carrier is considered promising to enable the encapsulation of tissue cells and their delivery into damaged target tissues, including bone with defect-tunability for bone tissue engineering.

Novel nanocomposite magnetic scaffolds demonstrated excellent bone cell responses.

In bone regeneration, silicon-based calcium phosphate glasses (Bioglasses) have been widely used since the 1970s. However, they dissolve very slowly because of their high amount of Si (SiO2 > 45%). Recently, our group has found that calcium ions released by the degradation of glasses in which the job of silicon is done by just 5% of TiO2 are effective angiogenic promoters, because of their stimulation of a cell-membrane calcium sensing receptor (CaSR). Based on this, other focused tests on angiogenesis have found that Bioglasses also have the potential to be angiogenic promoters even with high contents of silicon (80%); however, their slow degradation is still a problem, as the levels of silicon cannot be decreased any lower than 45%. In this work, we propose a new generation of hybrid organically modified glasses, ormoglasses, that enable the levels of silicon to be reduced, therefore speeding up the degradation process. Using electrospinning as a faithful way to mimic the extracellular matrix (ECM), we successfully produced hybrid fibrous mats with three different contents of Si (40, 52, and 70%), and thus three different calcium ion release rates, using an ormoglass-polycaprolactone blend approach. These mats offered a good platform to evaluate different calcium release rates as osteogenic promoters in an in vivo subcutaneous environment. Complementary data were collected to complement Ca(2+) release analysis, such as stiffness evaluation by AFM, ζ-potential, morphology evaluation by FESEM, proliferation and differentiation analysis, as well as in vivo subcutaneous implantations. Material and biological characterization suggested that compositions of organic/inorganic hybrid materials with a Si content equivalent to 40%, which were also those that released more calcium, were osteogenic. They also showed a greater ability to form blood vessels. These results suggest that Si-based ormoglasses can be considered an efficient tool for calcium release modulation, which could play a key role in the angiogenic promoting process.