Academic Sharing | DIW 3D Printed ROS Logic-Gated Multifunctional Scaffolds for Aged Bone Defect Repair

Abstract

The impaired regeneration of aged individuals presents major challenges for repairing bone defects. Within the senescent microenvironment (SME), excessive reactive oxygen species (ROS), chronic inflammation, the accumulation of senescent cells and local infection form a self-reinforcing vicious cycle that hinders healing. Here, we developed a multimodal ROS logic-gated therapeutic platform by integrating magnesium- and manganese-doped bismuth oxide with oxygen vacancies nanoparticles (MMBOx) embedded in a rapamycin (Rapa)-loaded, 3D-printed hydrogel scaffold. In vitro study, this platform combines pH-responsive peroxidase, oxidase-like activity and photothermal-enhanced sonodynamic effects, enabling on-demand ROS generation for efficient antibacterial elimination. Simultaneously, MMBOx and the hydrogel scavenge excess ROS, while Rapa promotes cellular autophagy to remove damaged mitochondria, enhances ROS regulation, and delays stem cell senescence. Moreover, MMBOx enhances glutathione (GSH) synthesis and metabolism by modulating the Keap1-Nrf2 signaling pathway, thereby boosting the intracellular GSH pool and increasing ROS tolerance to support a more youthful cellular phenotype. In vivo studies confirm that this platform alleviates infection in the infected skin defect model. Furthermore, it attenuates SME-associated chronic inflammation and cellular senescence, and promotes bone regeneration in the aged rat calvarial defect model. These findings offer a promising strategy for addressing deteriorated SME and enhancing bone repair in the elderly.

3D Printing Strategies Involved in This Research

1. Soongon Compatible Modules:

• Low-temperature Nozzle/Platform: Equipped with a low-temperature direct-writing nozzle/platform module. This module supports -5°C to room temperature, which can quickly improve curing efficiency and ensure the printing and molding effect of the material.
• Ink Extrusion Printing: Suitable for low-viscosity biomaterials, such as hydrogels, gelatin, etc.
• UV Light-Assisted Curing Module: Supports multiple wavelength ranges, effectively assisting the curing and molding of direct-writing materials containing photo-initiators.

Editor's Extended Ideas for This Research

1. Extension Concepts:

• Upgradable Multi-channel Printheads: Realizing the preparation of printed structures with different Ni-loading inks, providing a new way for biomaterial manufacturing.
• Online Mixing Module: To improve experimental efficiency, an online mixing module can be used to mix biomaterials with specific performance materials in real-time, satisfying more different printing methods during multi-nozzle collaboration.
• Rotating Shaft Module: Providing more experimental space for tubular scaffolds of different diameters and lengths.

2. Module Introduction:

• Multi-channel Printhead: 2-4 channel design, can carry multiple materials for collaborative/parallel printing.
• Active or Passive Mixing Modes: Can be mixed online in real-time to achieve specified ratio mixing materials and online gradient changes.
• Rotating Shaft Diameter Support: φ1.5, φ2, φ4, φ6, φ8, φ10, φ20, φ25.
• Rotating Shaft Printing Length: φ1.5, φ2, φ4, φ6, φ8, φ10 can print 100mm; φ20, φ25 can print 55mm.