The therapeutic precision and clinical applicability of drug-eluting coatings can be substantially improved by facilitating tunable drug delivery. However, the design of coatings which allows for precise control over drug release kinetics is still a major challenge. Here, a double-layered silk fibroin (SF) coating system was constructed by sequential electrophoretic deposition. A mixture of dissolved Bombyx mori SF (bmSF) molecules and pre-made bmSF nanospheres at different ratios was deposited as under-layer. Subsequently, this underlayer was covered by a top-layer comprising Antheraea pernyi SF (apSF) molecules (rich in arginylglycylaspartic acid, RGD) to improve the cellular response of the resulting double-layered coatings. Additionally, model drug doxycycline was either pre-mixed with dissolved bmSF molecules or pre-loaded into pre-made bmSF nanospheres at the same amount before their mixing and deposition. The thickness and nanosphere content of the under-layer architecture were proportional to the deposition time and nanosphere concentration in precursor mixtures, respectively. The surface topography, wettability, degradation rate and adhesion strength were comparable within the double-layered coating system. As expected, RGD-rich apSF top-layer improved cell adhesion, spreading and proliferation compared with bmSF top-layer. Furthermore, the amount and duration of drug release increased linearly with increasing nanosphere concentration at fixed deposition time, whereas drug release amount increased linearly with increasing deposition time. These results indicate that the dosage and kinetics of loaded drugs can be quantitatively tailored by altering nanosphere concentration and deposition time as main processing parameters. Overall, this study illustrates the strong potential of pre-defining coating architecture to facilitate control over drug delivery.

Although with the good biological properties, silk fibroin (SF) is immensely restrained in long-distance vascular defect repair due to its relatively fast degradation and inferior mechanical properties. It is necessary to construct a multifunctional composite scaffold based on SF. In this study, a novel magnetic SF scaffold (MSFCs) was prepared by an improved infiltration method. Compared with SF scaffold (SFC), MSFCs were found to have better crystallinity, magnetocaloric properties, and mechanical strength, which was ascribed to the rational introduction of iron-based magnetic nanoparticles (MNPs). Moreover, in vivo and in vitro experiments demonstrated that the degradation of MSFCs was significantly extended. The mechanism of delayed degradation was correlated with the dual effect that was the newly formed hydrogen bonds between SFC and MNPs and the complexing to tyrosine (Try) to inhibit hydrolase by internal iron atoms. Besides, the β-crystallization of protein in MSFCs was increased with the rise of iron concentration, proving the beneficial effect after MNPS doped. Furthermore, although macrophages could phagocytose the released MNPs, it did not affect their function, and even a reasonable level might cause some cytokines to be upregulated. Finally, in vitro and in vivo studies demonstrated that MSFCs showed excellent biocompatibility and the growth promotion effect on CD34-labeled vascular endothelial cells (VECs). In conclusion, we confirm that the doping of MNPs can significantly reduce the degradation of SFC and thus provide an innovative perspective of multifunctional biocomposites for tissue engineering.

Despite the progress made to improve therapeutic outcomes for acute myeloid leukemia (AML), many unmet clinical needs remain to be resolved. Unlike existing anti-AML strategies, here we developed a biomimetic nanocomposite to efficiently eliminate the leukemia cells in the bone marrow and prevent the homing of AML. To fulfill our design, the ultra-small nanozyme was conjugated onto the surface of an oxygen-carrying nanoparticle, which was further coated with bone marrow stromal cell membrane. After entering the blood, this biomimetic nanocomposite got actively internalized by the leukemia cells in the blood and released the loaded chemotherapeutics and nanozyme inside the leukemia cells to achieve a synergistic antitumor efficacy. Meanwhile, the adhesive properties of the stromal cell membrane enabled the nanocomposite to home to the bone marrow, where the nanocomposite effectively killed the retained leukemia cells. More importantly, the biomimetic cell membrane also acted as a CXCR4 antagonism to block the CXCR4/CXCL12-mediated homing of leukemia cells to the bone marrow and infiltration to other organs like the liver and spleen. In conclusion, this proof-of-concept study demonstrated that our designed platform effectively kills leukemia cells while preventing their infiltration, thus providing a promising prospect for resolving the clinical challenges in current AML treatment.

Bacterial keratitis is the most common corneal infection which may lead to blindness, and seriously threatened the human visual health worldwide. Clinical treatment with antibiotic eye drops formulation usually falls in low bioavailability and poor therapeutic efficiency. Hydrogel has gained much attention as ophthalmic formulation recently due to the prolonged drug retention on ocular surface. In this study, we proposed a type of all-small-molecule supramolecular hydrogel assembled from guanosine-5'-monophosphate disodium salt and tobramycin for the treatment of bacterial keratitis. Guanosine-5'-monophosphate disodium salt assembled into guanosine-quartet nanofibers via hydrogen bonding and π-π stacking, and tobramycin with five primary amine groups further crosslinked the nanofibers bearing multiple phosphate moieties into gel networks via ionic interactions. The supramolecular gel showed shear thinning and thixotropic properties, good biocompatibility, and antibacterial activity. The gel treatment significantly ameliorated P. aeruginosa induced bacterial keratitis, and showed higher therapeutic efficacy compared to tobramycin eye drop. This study provides a facile and efficient antibiotic gel formulation for clinical treatment of bacterial keratitis.