A Novel Cranial Bone Transport Technique Repairs Skull Defect and Minimizes Brain Injury Outcome in Traumatic Brain Injury Rats

TBI (traumatic brain injury) is a major cause of mortality and morbidity among young adults with limited therapeutic strategies. Cranial bone transport (CBT) technique is a safe, less invasive, and relatively simple surgical technique in bone reconstruction, which has been used to repair cranial bone defects and deformity corrections. The current studies are to determine the effects of CBT surgery on cranial bone regeneration as well as neurological functional recovery in TBI. CBT treatment alleviated lesion size and promoted learning, motor, and memory recovery in TBI rats. The meningeal lymphatic drainage function is enhanced, evidenced by increased intake of ovalbumin conjugated with Alexa Flour 647(OVA-A647) in meningeal lymphatic vessels (MLVs) and deep cervical lymph nodes (dCLNs). CBT accelerated P-tau clearance while decreasing Iba1 induced neuroinflammatory response in TBI rats. Notably, improvement of CBT treatment is significantly abolished by the ablation of MLVs via MAZ51, a small-molecule inhibitor primarily targeting vascular endothelial growth factor receptor-3 (VEGFR-3). Furthermore, after bone transport treatment, bone regeneration in the CBT sites continued consolidation, bone defects in TBI are replaced with new bone more quickly after CBT surgery. Taken together, the study is a proof-of-concept de-novo study to prove CBT can significantly improve the outcomes of brain recovery and cranioplasty in TBI rats.