Controlled and Local Delivery of Antibiotics by 3D Core/Shell Printed Hydrogel Scaffolds to Treat Soft Tissue Infections.

Soft tissue infections in open fractures or burns are major cause for high morbidity in trauma patients. Sustained, long-term and localized delivery of antimicrobial agents is needed for early eradication of these infections. Traditional (topical or systemic) antibiotic delivery methods are associated with a variety of problems, including their long-term unavailability and possible low local concentration. Novel approaches for antibiotic delivery via wound coverage/healing scaffolds are constantly being developed. Many of these approaches are associated with burst release and thus seldom maintain long-term inhibitory concentrations. Using 3D core/shell extrusion printing, scaffolds consisting of antibiotic depot (in the core composed of low concentrated biomaterial ink 3% alginate) surrounded by a denser biomaterial ink (shell) were fabricated. Denser biomaterial ink (composed of alginate and methylcellulose or alginate, methylcellulose and Laponite) retained scaffold shape and modulated antibiotic release kinetics. Release of antibiotics was observed over seven days, indicating sustained release characteristics and maintenance of potency. Inclusion of Laponite in shell, significantly reduced burst release of antibiotics. Additionally, the effect of shell thickness on release kinetics was demonstrated. Amalgamation of such a modular delivery system with other biofabrication methods could potentially open new strategies to simultaneously treat soft tissue infections and aid wound regeneration.

Tailorable Zinc-Substituted Mesoporous Bioactive Glass/Alginate-Methylcellulose Composite Bioinks.

Bioactive glasses have been used for bone regeneration applications thanks to their excellent osteoconductivity, an osteostimulatory effect, and high degradation rate, releasing biologically active ions. Besides these properties, mesoporous bioactive glasses (MBG) are specific for their highly ordered mesoporous channel structure and high specific surface area, making them suitable for drug and growth factor delivery. In the present study, calcium (Ca) (15 mol%) in MBG was partially and fully substituted with zinc (Zn), known for its osteogenic and antimicrobial properties. Different MBG were synthesized, containing 0, 5, 10, or 15 mol% of Zn. Up to 7 wt.% of Zn-containing MBG could be mixed into an alginate-methylcellulose blend (algMC) while maintaining rheological properties suitable for 3D printing of scaffolds with sufficient shape fidelity. The suitability of these composites for bioprinting applications has been demonstrated with immortalized human mesenchymal stem cells. Uptake of Ca and phosphorus (P) (phosphate) ions by composite scaffolds was observed, while the released concentration of Zn2+ corresponded to the initial amount of this ion in prepared glasses, suggesting that it can be controlled at the MBG synthesis step. The study introduces a tailorable bioprintable material system suitable for bone tissue engineering applications.

Bioprinting of Magnetically Deformable Scaffolds.

Mechanical stimulation of cells embedded in scaffolds is known to increase the cellular performance toward osteogenic or chondrogenic differentiation and tissue development. Three-dimensional bioplotting of magnetically deformable scaffolds enables the spatially defined distribution of magnetically inducible scaffold regions. In this study, a magnetic bioink based on alginate (alg, 3%) and methylcellulose (MC, 9%) with incorporated magnetite microparticles (25% w/w) was developed and characterized. The size and shape of particles were monitored via scanning electron microscopy and X-ray micro-computed tomography. Shear-thinning properties of the algMC ink were maintained after the addition of different concentrations of magnetite microparticles to the ink. Its viscosity proportionally increased with the added amount of magnetite, and so did the level of saturation magnetization as determined via vibrating sample magnetometry. The printability and shape fidelity of various shapes were evaluated, so that the final composition of algMC + 25% w/w magnetite was chosen. With application of this ink, cytocompatibility was proven in indirect cell culture and bioplotting experiments using a human mesenchymal stem cell line. Toward the deformation of cell-laden scaffolds to support cell differentiation in the future, radiography allowed the real-time monitoring of magnetically induced deformation of scaffolds of different pore architectures and scaffold orientations inside the magnetic field. Varying the strand distance and scaffold design will allow fine-tuning the degree of deformation in stimulatory experiments.