3D-printed biphasic core/shell hydrogel scaffolds with hybrid bioactive nanoparticles reinforcing core phase possessed controlled swelling, mechanical stiffness and dual-ranged pore size. They provided prominent osteoconductivity, biocompatibility and in-vivo osteogenicity.

There is a constant demand for novel materials/biomedical devices to accelerate the healing of hard-to-heal wounds. Herein, an innovative 3D-printed bioinspired construct was developed as an antibacterial/regenerative scaffold for diabetic wound healing. Hyaluronic/chitosan (HA/CS) ink was used to fabricate a bilayer scaffold comprising a dense plain hydrogel layer topping an antibacterial/regenerative nanofibrous layer obtained by incorporating the hydrogel with polylactic acid nanofibrous microspheres (MS). These were embedded with nano ZnO (ZNP) or didecyldimethylammonium bromide (DDAB)-treated ZNP (D-ZNP) to generate the antibacterial/healing nano/micro hybrid biomaterials, Z-MS@scaffold and DZ-MS@scaffold. Plain and composite scaffolds incorporating blank MS (blank MS@scaffold) or MS-free ZNP@scaffold and D-ZNP@scaffold were used for comparison. 3D printed bilayer constructs with customizable porosity were obtained as verified by SEM. The DZ-MS@scaffold exhibited the largest total pore area as well as the highest water-uptake capacity and in vitro antibacterial activity. Treatment of Staphylococcus aureus-infected full thickness diabetic wounds in rats indicated superiority of DZ-MS@scaffold as evidenced by multiple assessments. The scaffold afforded 95% wound-closure, infection suppression, effective regulation of healing-associated biomarkers as well as regeneration of skin structure in 14 d. On the other hand, healing of non-diabetic acute wounds was effectively accelerated by the simpler less porous Z-MS@scaffold. Information is provided for the first-time on the 3D printing of nanofibrous scaffolds using non-electrospun injectable bioactive nano/micro particulate constructs, an innovative ZNP-functionalized 3D-printed formulation and the distinct bioactivity of D-ZNP as a powerful antibacterial/wound healing promotor. In addition, findings underscored the crucial role of nanofibrous-MS carrier in enhancing the physicochemical, antibacterial, and wound regenerative properties of DDAB-nano ZnO. In conclusion, innovative 3D-printed DZ-MS@scaffold merging the MS-boosted multiple functionalities of ZNP and DDAB, the structural characteristics of nanofibrous MS in addition to those of the 3D-printed bilayer scaffold, provide a versatile bioactive material platform for diabetic wound healing and other biomedical applications.

Oral candidiasis (OC) is an opportunistic fungal infection, common amongst the elderly and the immunocompromised. Unfortunately, the therapeutic efficacy of common antifungals is imperiled by the rise of antifungal drug resistance. An alternative promising therapeutic option possibly contributing to antifungal therapy is drug repurposing. Herein, we aimed to employ novel pharmaceutical drug delivery for enhancing the emerging antifungal potential of the hypocholesterolemic drug atorvastatin (ATV). ATV-propylene-glycol-liposomes (ATV/PG-Lip) were prepared then integrated in 3D-printed (3DP) mucoadhesive films comprising chitosan, polyvinyl-alcohol and hydroxypropyl methylcellulose, as an innovative blend, for the management of OC. ATV/PG-Lip demonstrated good colloidal properties of particle size (223.3 ± 2.1 nm), PDI (0.12 ± 0.001) and zeta potential (-18.2 ± 0.3 mV) with high entrapment efficiency (81.15 ± 1.88%) and sustained drug release. Also, ATV/PG-Lip showed acceptable three-month colloidal stability and in vitro cytocompatibility on human gingival fibroblasts. The developed 3DP-films exhibited controlled ATV release (79.4 ± 1.4% over 24 h), reasonable swelling and mucoadhesion (2388.4 ± 18.4 dyne/cm²). In vitro antifungal activity of ATV/PG-Lip was confirmed against fluconazole-resistant Candida albicans via minimum inhibitory concentration determination, time-dependent antifungal activity, agar diffusion and scanning electron microscopy. Further, ATV/PG-Lip@3DP-film exceeded ATV@3DP-film in amelioration of infection and associated inflammation in an in vivo oral candidiasis rabbit model. Accordingly, the results confirm the superiority of the fabricated ATV/PG-Lip@3DP-film for the management of oral candidiasis and tackling antifungal resistance. Graphical abstract

Phytotherapeutics is widely used nowadays as an alternative to the current antifungal drugs to reduce their side effects. Curcumin, with its wide therapeutic array as antioxidant and anti-inflammatory agent, is one of the natural compounds that ha..s an antifungal effect, especially when being used at nanoscale to increase its bioavailability. Our research aimed to evaluate clinically and microbiologically the effect of using topical nanocurcumin suspension to treat oral candidiasis. After 4 days from induction of oral candidiasis (baseline), we randomly divided 39 female BALB/c mice into three groups of 13 animals; nanocurcumin, nystatin, and sham groups. All animals in nanocurcumin and nystatin groups received topical treatment twice daily for 10 days. Then, we performed clinical and microbiological evaluations at baseline, day 5, and day 10. By the end of treatment, our results revealed that nanocurcumin promoted a significant reduction in the number of candida colonies. There was no statistically significant difference neither clinically nor microbiologically between nanocurcumin and nystatin groups. In conclusion, nanocurcumin has a good antifungal effect as nystatin, however, its therapeutic efficacy takes a longer time to appear than nystatin. The enhanced bioavailability of curcumin at the nanoscale qualifies this nano-herb as a promising alternative therapy for oral candidiasis, evading nystatin-associated morbidity.