Designing of a Multifunctional 3D-Printed Biomimetic Theragenerative Aerogel Scaffold via Mussel-Inspired Chemistry: Bioactive Glass Nanofiber-Incorporated Self-Assembled Silk Fibroin with Antibacterial, Antiosteosarcoma, and Osteoinductive Properties.

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.

MXene-Integrated Silk Fibroin-Based Self-Assembly-Driven 3D-Printed Theragenerative Scaffolds for Remotely Photothermal Anti-Osteosarcoma Ablation and Bone Regeneration.

Aiming to address the bone regeneration and cancer therapy functionalities in one single material, in this study, we developed a dual-functional theragenerative three-dimensional (3D) aerogel-based composite scaffold from hybridization of photo-cross-linked silk fibroin (SF) biopolymer with MXene (Ti3C2) two-dimensional (2D) nanosheets. To fabricate the scaffold, we first develop a dual-cross-linked SF-based aerogel scaffold through 3D printing and photo-cross-linking of the self-assembly-driven methacrylate-modified SF (SF-MA) gel with controlled pore size, macroscopic geometry, and mechanical stability. In the next step, to endow a remotely controlled photothermal antiosteosarcoma ablation function to fabricated aerogel scaffold, MXene 2D nanosheets with strong near-infrared (NIR) photon absorption properties were integrated into the 3D-printed scaffolds. While 3D-printed MXene-modified dual-cross-linked SF composite scaffolds can mediate the in vitro growth and proliferation of preosteoblastic cell lines, they also endow a strong photothermal effect upon remote irradiation with NIR laser but also significantly stimulate bone mineral deposition on the scaffold surface. Additionally, besides the local release of the anticancer model drug, the generated heat (45-53 °C) mediated the photothermal ablation of cancer cells. The developed aerogel-based composites and chosen therapeutic techniques are thought to render a significant breakthrough in biomaterials' future clinical applications.

Self-Assembly-Driven Bi2S3 Nanobelts Integrated a Silk-Fibroin-Based 3D-Printed Aerogel-Based Scaffold with a Dual-Network Structure for Photothermal Bone Cancer Therapy.

Multifunctional all-in-one biomaterial combining the therapeutic and regeneration functionalities for successive tumor therapy and tissue regeneration is in high demand in interdisciplinary research. In this study, a three-dimensional (3D) aerogel-based composite scaffold with a dual-network structure generated through self-assembly and photo-cross-linking with combined properties of photothermally triggered controlled anticancer drug release and photothermal cancer cell ablation was successfully fabricated. The fabrication of composites consists of self-assembly of a silk fibroin methacrylate (SF-MA) biopolymer incorporated with hydrothermally driven bismuth sulfide (Bi2S3) methacrylate nanobelts, followed by a photo-cross-linking-assisted 3D-printing process. The developed scaffolds presented hierarchically organized porosity and excellent photothermal conversion thanks to the strong near-infrared (NIR) photon absorption of incorporated Bi2S3 nanobelts inside the scaffold matrix. The heat generated in the scaffold mediated by laser irradiation has not only triggered controlled and prolonged release of the anticancer drug but also significantly ablated the bone cancer cells adhered on the scaffold. In addition, the developed 3D composite scaffolds have demonstrated excellent biodegradability for organic and inorganic network constituents at different media, enabling them as potential implants to be replaced by de novo tissue. In combination of chemotherapy and photothermal therapy, the multifunctional 3D-printed composite aerogel scaffold is expected to be an excellent implantable material in bone tissue engineering (BTE) for successive cancer therapy and tissue regeneration.