## 8 Functional Aspects of Honey-Loaded Scaffolds for Wound Healing  
Every health condition to be treated and every specific application of a therapeutic device requires specific features in order to obtain the best possible mitigation of the symptoms or achieve a full recovery. In the design process of a loaded scaffold, an accurate evaluation of the most suitable polymer to be employed depends on the required functions, e.g., the tensile strength for scaffolds destined to areas subjected to intense mechanical stress, the ability to improve cell proliferation for hydrogels for wound healing, and antimicrobial properties for infected wounds. For example, wider inhibition zones on a disc diffusion test were measured for chitosan-based honey hydrogels than for those fabricated with carbopol, indicating a higher antimicrobial activity in vitro, when equal honey concentrations were compared. Furthermore, the 75% honey-chitosan hydrogel showed better antibacterial performance than pure honey when evaluated using the disc diffusion method against four common burn-infecting bacteria, and it also induced the fastest burn wound closure among the tested preparations [161]. These results could be attributed to the intrinsic potential of chitosan for biomedical applications [162; 163] which seemingly potentiated and improved honey's virtues. These results could be attributed to the intrinsic potential of chitosan for biomedical applications [162; 163], which seemingly potentiated and improved honey's virtues. Honey incorporation into a scaffold and its penetration into the tridimensional polymer network has also been shown to alter the mechanical performance by inducing structural modifications. This might potentially improve some functional attributes and negatively affect others; therefore, the concentration of honey has to be carefully evaluated in order to accurately tailor the scaffold's behaviour based on the specifics of the tissue to be treated. Chestnut honey incorporation on carboxymethyl cellulose (CMC) hydrogels affected the structural strength with reduced capacity to withstand compression load compared to plain CMC gels [134]. This should be kept in mind as it might assume greater importance depending on the location of the wound to be treated to ensure that the hydrogel maintains structural integrity throughout the application time. Interestingly, in a study by [PERSON] et al., Manuka honey was exploited as molecular spacer in gellam gum hydrogels for cartilage implants, with improved compressive moduli and flexibility. Furthermore, these cytocompatible hydrogels induced chondrogenic differentiation with the deposition of cartilage integral constituents such as collagen II, glycosaminoglycans (GAGs), and proteoglycans, which resulted in effective cartilage reconstruction. When tested against MDR _Staphylococci_ pathogens typically isolated in post-arthroscopy infected joints, the scaffolds have been shown to significantly reduce the biofilm viability in comparison with controls at each time point [164]. Honey addition (up to 2%) to alginate bioink reduced its viscosity in a dose-dependent way without appreciably affecting the overall rheological features such as extrusion and printability. However, honey significantly enhanced fibroblast viability, proliferation, and adhesion when compared with the plain alginate membrane, with promising applicability to bioprint compatible bioengineered human skin tissues substitutes [165]. These contrasting results indicate that the impact of honey incorporation on the scaffold functionality cannot be assumed and should be evaluated as a matter of course, as the biomedical outcome cannot prescind from an optimised structural and mechanical performance.