Since the last few decades, the development of smart hydrogels, which can respond to stimuli and adapt their responses based on external cues from their environments, has become a thriving research frontier in the biomedical engineering field. Nowadays, drug delivery systems have received great attention and smart hydrogels can be potentially used in these systems due to their high stability, physicochemical properties, and biocompatibility. Smart hydrogels can change their hydrophilicity, swelling ability, physical properties, and molecules permeability, influenced by external stimuli such as pH, temperature, electrical and magnetic fields, light, and the biomolecules’ concentration, thus resulting in the controlled release of the loaded drugs. Herein, this review encompasses the latest investigations in the field of stimuli-responsive drug-loaded hydrogels and our contribution to this matter.

Along with biocompatibility, bioinductivity and appropriate biodegradation, mechanical properties are also of crucial importance for tissue engineering scaffolds. Hydrogels, such as gellan gum (GG), are usually soft materials, which may benefit from the incorporation of inorganic particles, e.g. bioactive glass, not only due to the acquired bioactivity, but also due to improved mechanical properties. They exhibit complex viscoelastic properties, which can be evaluated in various ways. In this work, to reliably evaluate the effect of the bioactive glass (BAG) addition on viscoelastic properties of the composite hydrogel, we employed and compared the three most commonly used techniques, analyzing their advantages and limitations: monotonic uniaxial unconfined compression, small amplitude oscillatory shear (SAOS) rheology and dynamic mechanical analysis (DMA). Creep and small amplitude dynamic strain-controlled tests in DMA are suggested as the best ways for the characterization of mechanical properties of hydrogel composites, whereas the SAOS rheology is more useful for studying the hydrogel’s processing kinetics, as it does not induce volumetric changes even at very high strains. Overall, the results confirmed a beneficial effect of BAG (nano)particles on the elastic modulus of the GG–BAG composite hydrogel. The Young’s modulus of 6.6 ± 0.8 kPa for the GG hydrogel increased by two orders of magnitude after the addition of 2 wt.% BAG particles (500–800 kPa).

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Titanium‐based implants are widely used in modern clinical practice; however, complications associated with implants due to bacterial‐induced infections arise frequently, caused mainly by staphylococci, streptococci, Pseudomonas spp. and coliform bacteria. Although increased hydrophilicity of the biomaterial surface is known to be beneficial in minimizing the biofilm, quantitative analyses between the actual implant parameters and bacterial development are scarce. Here, the results of in vitro studies of Staphylococcus aureus and Staphylococcus epidermidis proliferation on uncoated and coated titanium materials with different roughness, porosity, topology, and hydrophilicity are shown. The same materials have been tested in parallel with respect to human osteogenic and endothelial cell adhesion, proliferation, and differentiation. The experimental data processed by meta‐analysis are indicating the possibility of decreasing the biofilm formation by 80–90% for flat substrates versus untreated plasma‐sprayed porous titanium and by 65–95% for other porous titanium coatings. It is also shown that optimized surfaces would lead to 10–50% enhanced cell proliferation and differentiation versus reference porous titanium coatings. This presents an opportunity to manufacture implants with intrinsic reduced infection risk, yet without the additional use of antibacterial substances.

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Orthopedic metallic devices are often related with devasting complications due to acute prosthetic joint infections. Gallium (Ga) antibacterial activity has been demonstrated by the evidence that Ga in solution ionizes in a Ga3+ trivalent form that replace Fe3+ thus arresting metabolism. However, it is not clear whether such effect is restricted only to Ga3+ release laps. Accordingly, here we investigated Ga addition into titanium alloys using metallurgical methods, thus realizing intermetallides of a very high stability that contain Ga in the range of 1, 2, 20, and 23% wt. ICP-OES analysis confirmed that Ga ions were not released from the specimens regardless of the Ga amount. These alloys ensured long-lasting Ga effect toward multidrug resistant Staphylococcus aureus, whose metabolic activity was reduced of >80% in comparison with controls. Finally, specimens cytocompatibility was confirmed by direct and indirect contact evaluations with mature osteoblasts and preosteoblasts progenitor cells.

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