Abstract: Dura closure following surgery for traumatic brain injury is important to maintain the structural integrity of the brain and serve as a barrier to prevent infection and leakage of cerebrospinal fluid. Although an artificial dural mater can provide barrier capabilities, its performance in the repair of injured neural cells and neuroprotection during the secondary injury stage can be improved. Therefore, we designed and manufactured a multi-layer nanofibrous dura mater containing minocycline and insulin-like growth factor 1 using electrospinning technology to repair tissue following traumatic brain injury. The results showed that the multi-layer nanofibrous dura mater promoted neuronal process transection, hypoxia, and glucose deprivation, as well as survival and neurite extension of SH-SY5Y cells after oxidative stress injury. Minocycline hydrochloride and insulin growth factor 1 were separately incorporated into the fibers to facilitate their differential dual release for immunomodulation during the early stage of traumatic brain injury and provide neuroprotection during the repair process. In addition, the multi-layered nanofibrous dura mater promoted the increase in M2 polarization for microglia and the secretion of anti-inflammatory cytokines, which enhanced neural cell survival. Furthermore, we verified the antibacterial, anti-adhesion, barrier performance, anti-leakage, and biocompatibility capabilities of the multi-layered nanofibrous dura mater. Therefore, our multi-layered nanofibrous dura mater containing minocycline and insulin-like growth factor 1 has great potential as a substitute for dura mater and promotes nerve recovery following traumatic brain injury.

Key words: anti-adhesion, antibacterial, anti-inflammatory, anti-leakage, barrier performance, biocompatibility, differential dual-release, multilayered nanofibrous dura mater, neuroprotection, traumatic brain injury, nerve regeneration