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.

Fabrication of Antibacterial, Osteo-Inductor 3D Printed Aerogel-Based Scaffolds by Incorporation of Drug Laden Hollow Mesoporous Silica Microparticles into the Self-Assembled Silk Fibroin Biopolymer.

In this study, the novel biomimetic aerogel-based composite scaffolds through a synergistic combination of wet chemical synthesis and advanced engineering approaches have successfully designed. To this aim, initially the photo-crosslinkable methacrylated silk fibroin (SF-MA) biopolymer and methacrylated hollow mesoporous silica microcapsules (HMSC-MA) as the main constituents of the novel composite aerogels were synthesized. Afterward, by incorporation of drug-loaded HMSC-MA into the self-assembled SF-MA, printable gel-based composite inks are developed. By exploiting micro-extrusion-based three-dimensional (3D) printing, SF-MA-HMSC composite gels are printed by careful controlling their viscosity to provide a means to control the shape fidelity of the resulted printed gel constructs. The developed scaffold has shown a multitude of interesting biophysical and biological performances. Namely, thanks to the photo-crosslinking of the gel components during the 3D printing, the scaffolds become mechanically more stable than the pristine SF scaffolds. Also, freeze-casting the printed constructs generates further interconnectivity in the printed pore struts resulting in the scaffolds with hierarchically organized porosities necessary for cell infiltration and growth. Importantly, HMSC incorporated scaffolds promote antibacterial drug delivery, cellular ingrowth and proliferation, promoting osteoblastic differentiation by inducing the expression of osteogenic markers and matrix mineralization. Finally, the osteoconductive, -inductive, and anti-infective composite aerogels are expected to act as excellent bone implanting materials with an extra feature of local and sustained release of drug for efficient therapy of bone-related diseases.

3D Printing of Antibacterial, Biocompatible, and Biomimetic Hybrid Aerogel-Based Scaffolds with Hierarchical Porosities via Integrating Antibacterial Peptide-Modified Silk Fibroin with Silica Nanostructure.

Scaffold-mediated tissue engineering has become a golden solution for the regeneration of damaged bone tissues that lack self-regeneration capability. A successful scaffold in bone tissue engineering comprises a multitude of suitable biological, microarchitectural, and mechanical properties acting as different signaling cues for the cells to mediate the new tissue formation. Therefore, careful design of bioactive scaffold macro- and microstructures in multiple length scales and biophysical properties fulfilling the tissue repair demands are necessary yet challenging to achieve. Herein, we have developed an antibacterial and biocompatible silica-silk fibroin (SF) gel-based ink through novel yet simple chemical approaches of sol-gel and self-assembly followed by processing the obtained gels as three-dimensional (3D) hybrid aerogel-based scaffolds exploiting the advanced materials design approaches of micro-extrusion-based 3D printing, and directional freeze-casting/drying approaches. As the main constituent of the hybrid biocompatible scaffold of this study, we used the SF extracted from Bombyx mori silkworm cocoon. However, to increase the cell responsivity and bactericidal efficiency of the final scaffold, thiol-ended antimicrobial and cell adhesive peptide sequence (SH-CM-RGD) was conjugated to silica-SF hybrid gels via covalent attachment using a spacer molecule through either preprint (prior to sol-gel) or during the post-printing steps on the previously printed silica-SF gel. In the next step, the hybrid Silica-SF-CM-RGD hydrogel ink was 3D-printed into the construct with interconnected porous structure with hierarchically organized porosity and a combination of several promising properties. Namely, due to the covalent linkage of the antibacterial peptide to the SF, the scaffold shows potent bactericidal efficiency toward Gram-positive and Gram-negative bacteria. Moreover, nanostructured silica components in the 3D-printed composites could intertwine with SF-CM-RGD to support the mechanical properties in the final scaffold and the final osteoconductivity of the scaffold. This study supports the promising properties of 3D-printed silica-SF-based hybrid aerogels constructs for repairing bone defect.

Nacre-Mimetic, Mechanically Flexible, and Electrically Conductive Silk Fibroin-MXene Composite Foams as Piezoresistive Pressure Sensors.

The hierarchical nacre-like three-dimensional (3D) assembly of porous and lightweight materials is in high demand for applications such as sensors, flexible energy storage and harvesting devices, electromagnetic interference shielding, and biomedical applications. However, designing such a biomimetic hierarchical architecture is highly challenging due to the lack of experimental approaches to achieve the necessary control over the materials' microstructure on the multilength scale. Aerogels and foam-based materials have recently been developed as attractive candidates for pressure-sensing applications. However, despite recent progress, the bottleneck for these materials to achieve electrical conductivity combined with high mechanical flexibility and fast strain recovery remains. In this study, for the first time, inspired by the multiscale architecture of nacre, we fabricated a series of ultra-lightweight, flexible, electrically conductive, and relatively high-strength composite foams through hybridizing the cross-linked silk fibroin (SF) biopolymer, extracted from Bombyx mori silkworm cocoon, reinforced with two-dimensional graphene oxide (GO) and Ti3C2 MXene nanosheets. Nacre is a naturally porous material with a lightweight, mechanically robust network structure, thanks to its 3D interconnected lamella-bridge micromorphology. Inspired by this material, we assemble a cross-linked SF fibrous solution with MXene and GO nanosheets into nacre-like architecture using a bidirectional freeze-casting technique. Subsequent freeze-drying and gas-phase hydrophobization resulted in composite foams with 3D hierarchical porous architectures with a unique combination of mechanical resilience, electrical conductance, and ultra-lightness. The developed composite presented excellent performances as piezoresistive pressure-sensing devices and sorbents for oil/water separation, which indicated great potential in mechanically switchable electronics.