Gelatin methacrylate hydrogel with drug-loaded polymer microspheres as a new bioink for 3D bioprinting.

3D bioprinted hydrogel constructs are advanced systems of a great drug delivery application potential. One of the bioinks that has recently gained a lot of attention is gelatin methacrylate (GelMA) hydrogel exhibiting specific properties, including UV cross-linking possibility. The present study aimed to develop a new bioink composed of GelMA and gelatin modified by addition of polymer (polycaprolactone or polyethersulfone) microspheres serving as bioactive substance carriers. The prepared microspheres suspension in GelMA/gelatin bioink was successfully bioprinted and subjected to various tests, which showed that the addition of microspheres and their type affects the physicochemical properties of the printouts. The hydrogel stability and structure was examined using scanning electron and optical microscopy, its thermal properties with differential scanning calorimetry and thermogravimetric analysis and its biocompatibility on HaCaT cells using viability assay and electron microscopy. Analyses also included tests of hydrogel equilibrium swelling ratio and release of marker substance. Subsequently, the matrices were loaded with ampicillin and the antibiotic release was validated by monitoring the antibacterial activity on Staphylococcus aureus and Escherichia coli. It was concluded that GelMA/gelatin bioink is a good and satisfying material for potential medical use. Depending on the polymer used, the addition of microspheres improves its structure, thermal and drug delivery properties.

Electrospun UV-cross-linked polyvinylpyrrolidone fibers modified with polycaprolactone/polyethersulfone microspheres for drug delivery.

Electrospun fibers, often used as drug delivery systems, have two drawbacks - in the first stage of their action a sudden active substance burst release occurs and they have a relatively small capacity for a drug. In this work the fibers are modified by the addition of drug-loaded microspheres acting as micro-containers for the drug and increasing the total drug capacity of the system. Its release from such a structure is slowed down by placing the microspheres inside the fibers so they are covered with an outer layer of fiber-forming polymer. The work presents a new method (microsphere suspension electrospinning) of obtaining polyvinylpyrrolidone fibers cross-linked with UV light modified with polycaprolactone/polyethersulphone microspheres loaded with active substance - rhodamine 640 as a marker or ampicillin as a drug example. The influence of UV-cross-linking time and the microspheres addition on the degradation, mechanical strength and transport properties of fibrous mats was investigated. The mats were insoluble in water, in some cases mechanically stronger, their drug capacity was increased and the burst effect was eliminated. The antibacterial properties of ampicillin-loaded mats were confirmed. The product of proposed suspension electrospinning process has application potential as a drug delivery system.

Development of a new 3D bioprinted antibiotic delivery system based on a cross-linked gelatin-alginate hydrogel.

3D bioprinting uses bioink deposited directly on a collector to create any previously designed 3D model. One of the most common and the easiest to operate bioinks is gelatin-alginate hydrogel. The present study aimed to combine 3D bioprinting with different cross-linking techniques to develop a new stable and biodegradable gelatin-alginate hydrogel matrix for drug delivery applications. The matrix-building biopolymers were crosslinked by ionotropic gelation with Ca2+ ions, chemical crosslinking with GTA or a combination of the two crosslinkers at various concentrations. The influence of the crosslinking method on the hydrogel properties, stability and structure was examined using scanning electron and optical microscopy, differential scanning calorimetry and thermogravimetric analysis. Analyses included tests of hydrogel equilibrium swelling ratio and release of marker substance. Subsequently, biological properties of the matrices loaded with the antibiotic chlorhexidine were studied, including cytotoxicity on HaCAT cells and antibacterial activity on Staphylococcus aureus and Escherichia coli bacteria. The conducted study confirmed that the 3D bioprinted cross-linked drug-loaded alginate-gelatin hydrogel is a good and satisfying material for potential use as a drug delivery system.

In vitro evaluation of electrochemically bioactivated Ti6Al4V 3D porous scaffolds.

Triply periodic minimal surfaces (TPMS) are known for their advanced mechanical properties and are wrinkle-free with a smooth local topology. These surfaces provide suitable conditions for cell attachment and proliferation. In this study, the in vitro osteoinductive and antibacterial properties of scaffolds with different minimal pore diameters and architectures were investigated. For the first time, scaffolds with TPMS architecture were treated electrochemically by plasma electrolytic oxidation (PEO) with and without silver nanoparticles (AgNPs) to enhance the surface bioactivity. It was found that the scaffold architecture had a greater impact on the osteoblast cell activity than the pore size. Through control of the architecture type, the collagen production by osteoblast cells increased by 18.9% and by 43.0% in the case of additional surface PEO bioactivation. The manufactured scaffolds demonstrated an extremely low quasi-elastic modulus (comparable with trabecular and cortical bone), which was 5-10 times lower than that of bulk titanium (6.4-11.4 GPa vs 100-105 GPa). The AgNPs provided antibacterial properties against both gram-positive and gram-negative bacteria and had no significant impact on the osteoblast cell growth. Complex experimental results show the in vitro effectiveness of the PEO-modified TPMS architecture, which could positively impact the clinical applications of porous bioactive implants.

Effect of electrospinning process variables on the size of polymer fibers and bead-on-string structures established with a 23 factorial design.

This work examines the effect of selected process parameters on the diameter of uniform and heterogeneous fibers (with and without bead-on-string structures) and the size of beads obtained during the electrospinning process. A 23 factorial design was performed to determine the influence of the following factors: electrical voltage, flow rate and dynamic viscosity of the poly(vinylpyrrolidone) ethanolic solution. Factorial design enables the analysis of the mathematical relationship between the chosen factors and the response with a minimum number of experiments. The factor having the most significant impact on the size of beaded fibers and beads was the solution viscosity, while the voltage had the greatest influence on the bead-free fiber diameter. The interactions between the studied factors were also analyzed. It was found that the presented method can be used for the design of an optimal and cost-effective electrospinning process, allowing the desired product to be obtained with expected features.