A Novel 3D-Printed Bi-Layer Cranial-Brain Patch Promotes Brain Injury Repair and Bone Tissue Regeneration

Traumatic brain injury (TBI), recognized as the world's most serious public health problem, currently lacks effective treatment options. The development of the patch has great clinical significance whether it is used as a skull implant material or TBI repair. In response to this critical health challenge, a novel 3D-printed bi-layer cranial-brain patch (SMB6) with dual functionality, addressing both TBI repair and skull regeneration, is developed. In the first layer, the incorporation of high concentrations of mesoporous bioactive glass nanoparticles establishes a microenvironment for bone regeneration. Meanwhile, the second layer, comprised of methacrylated silk fibroin hydrogel, provides essential mechanical support for nanocell membrane vesicles loaded with macrophage colony-stimulating factor and interleukin-6. This innovative design aims to interrupt the cascade of secondary brain injury. In experimental models of TBI, SMB6 demonstrates remarkable efficacy in inhibiting brain edema, exerting therapeutic effects on blood vessels, nerves, and inflammation. Additionally, promising outcomes are observed in promoting bone regeneration in skull defect models. This work not only introduces a potential therapeutic patch for TBI-related diseases but also provides novel insights for the clinical translation of cranial patches. Schematic showing a novel 3D-printed bi-layer cranial-brain patch promotes traumatic brain injury repair and bone tissue regeneration. In the first layer, the incorporation of high concentrations of mesoporous bioactive glass establishes a microenvironment for bone regeneration. Meanwhile, the second layer is loaded with bio microglia that encapsulate macrophage colony-stimulating factor and interleukin-6 to block the secondary injury cascade.image