Zhang Bin, Bai Miao, Yang Mengshi, Wang Yumei, Chen Xiyu, Liu Baiyun, Shi Guangzhi
Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Neurology, The First Hospital of Tsinghua University, Beijing, China.
J Transl Med. 2025 May 23;23(1):579. doi: 10.1186/s12967-025-06528-w.
Glucocorticoids (GCs) have been widely used in the treatment of severe traumatic brain injury (TBI) to inhibit neuroinflammation and alleviating brain edema and cannot be replaced by other drugs. However, their systemic application still faces many obstacles, such as the poor blood-brain-barrier (BBB) penetration and severe side effects. Therefore, new treatment strategy or compounds are urgently needed in clinic.
Herein, an injectable nanocomposite hydrogel is developed as a biofunctionalized delivery platform for intraoperative administration of dexamethasone (DEX) after TBI. By using a mice TBI model, the safety and efficacy of the nanohydrogels in treating BBB disruption, brain edema and nerve injury were evaluated after TBI.
The hydrogel is composed of polysaccharide matrix (carboxymethyl chitosan and oxidized dextran) and mesoporous polydopamine (MPDA) nanoparticles loaded with DEX (MPDA@DEX@gel) that could realize in situ injection, self-assembly, a high DEX loading rate and sustained release around the lesion. The MPDA@DEX@gel exhibits excellent antibacterial and hemostatic properties, good biocompatibility and antioxidation, and self-healing capability in vitro. These in vitro and in vivo results show that local application of MPDA@DEX@gel not only alleviates brain edema, promotes neuronal survival, and improves neurological function by restoring the integrity of BBB and inhibiting neuroinflammation after TBI, but also effectively avoids the peripheral and central side effects.
Our study provides a promising treatment strategy for the rational use of GCs in patients with severe TBI.
糖皮质激素（GCs）已被广泛用于治疗重度创伤性脑损伤（TBI），以抑制神经炎症和减轻脑水肿，且无法被其他药物替代。然而，其全身应用仍面临诸多障碍，如血脑屏障（BBB）穿透性差和严重的副作用。因此，临床上迫切需要新的治疗策略或化合物。
在此，开发了一种可注射的纳米复合水凝胶，作为TBI后术中给予地塞米松（DEX）的生物功能化递送平台。通过使用小鼠TBI模型，评估纳米水凝胶在TBI后治疗BBB破坏、脑水肿和神经损伤的安全性和有效性。
该水凝胶由多糖基质（羧甲基壳聚糖和氧化葡聚糖）和负载DEX的介孔聚多巴胺（MPDA）纳米颗粒（MPDA@DEX@凝胶）组成，可实现原位注射、自组装、高DEX负载率以及在损伤部位周围持续释放。MPDA@DEX@凝胶在体外表现出优异的抗菌和止血性能、良好的生物相容性和抗氧化性以及自愈能力。这些体外和体内结果表明，局部应用MPDA@DEX@凝胶不仅可减轻脑水肿、促进神经元存活，并通过恢复BBB完整性和抑制TBI后的神经炎症来改善神经功能，还能有效避免外周和中枢副作用。
我们的研究为重度TBI患者合理使用GCs提供了一种有前景的治疗策略。
