RESUMEN
The aim of this study is to design a therapeutic enhanced three-dimensional (3D) silk fibroin (SF)-based scaffold containing propolis (Ps)-loaded chitosan (CH) nanocarriers. To this aim, we initially synthesized a hybrid gel-based ink by a synergistic sol-gel and self-assembly approach and then processed the resulting gels by microextrusion-based 3D printing followed by supercritical drying to obtain 3D hybrid aerogel scaffolds. Ps was utilized to enhance the final scaffold's bactericidal efficacy and cell responsiveness. For the synthesis of the scaffold, two Ps loading methods (in preprint and postprinting steps) were investigated in order to optimize the Ps drug quantities in the scaffold and maximize the antibacterial properties of scaffold. In the postprinting Ps loading step, the hybrid silica-oxidized SF (SFO)-CH hydrogel ink was 3D printed into a construct with an interconnected porous structure, and then, Ps was loaded into the printed construct. In the preprint loading method, PS was incorporated into the SF and a hydrolyzed silane solution prior to gelation. The morphological studies demonstrate that the addition of Ps encapsulated CH nanoparticles (NPs) into the hydrogel solution improved the porosity of the developed scaffolds. The rheological analysis of the designed gel ink with and without Ps loading and the release kinetics were studied. The antimicrobial results show that the Ps-loaded scaffolds in the postprinting step exhibited superior antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) strains compared to a preprinted Ps-loaded scaffold. Direct and indirect in vitro cytotoxicity tests also confirmed the designed Ps-loaded scaffold biocompatibility toward a mouse fibroblast (L929) cell line. We demonstrated that the scaffold formulated by propolis-loaded chitosan NPs can enhance the migration and proliferation of L929 fibroblast cells. The obtained results prove the promise of the designed 3D printed silica-SFO-CH-Ps scaffolds as a potent 3D scaffold to mediate tissue regeneration but also as an antibacterial highly porous matrix to support wound healing.
RESUMEN
Biomaterial-mediated bone tissue engineering (BTE) offers an alternative, interesting approach for the restoration of damaged bone tissues in postsurgery osteosarcoma treatment. This study focused on synthesizing innovative composite inks, integrating self-assembled silk fibroin (SF), tannic acids (TA), and electrospun bioactive glass nanofibers 70SiO2-25CaO-5P2O5 (BGNF). By synergistically combining the unique characteristics of these three components through self-assembly and microextrusion-based three-dimensional (3D) printing, our goal was to produce durable and versatile aerogel-based 3D composite scaffolds. These scaffolds were designed to exhibit hierarchical porosity along with antibacterial, antiosteosarcoma, and bone regeneration properties. Taking inspiration from mussel foot protein attachment chemistry involving the coordination of dihydroxyphenylalanine (DOPA) amino acids with ferric ions (Fe3+), we synthesized a tris-complex catecholate-iron self-assembled composite gel. This gel formation occurred through the coordination of oxidized SF (SFO) with TA and polydopamine-modified BGNF (BGNF-PDA). The dynamic nature of the coordination ligand-metal bonds within the self-assembled SFO matrix provided excellent shear-thinning properties, allowing the SFO-TA-BGNF complex gel to be extruded through a nozzle, facilitating 3D printing into scaffolds with outstanding shape fidelity. Moreover, the developed composite aerogels exhibited multifaceted features, including NIR-triggered photothermal antibacterial and in vitro photothermal antiosteosarcoma properties. In vitro studies showcased their excellent biocompatibility and osteogenic features as seeded cells successfully differentiated into osteoblasts, promoting bone regeneration in 21 days. Through comprehensive characterizations and biological validations, our antibacterial scaffold demonstrated promise as an exceptional platform for concurrent bone regeneration and bone cancer therapy, setting the stage for their potential clinical application.