Polydopamine-Decorated Microcomposites Promote Functional Recovery of an Injured Spinal Cord by Inhibiting Neuroinflammation

• Published in: ACS applied materials & interfaces 2021-10, Vol.13 (40), p.47341-47353
• Main Authors: Wei, Guangfei, Jiang, Dongdong, Hu, Shuai, Yang, Zhiyuan, Zhang, Zifan, Li, Wei, Cai, Weihua, Liu, Dongfei
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacokinetics; Anti-Inflammatory Agents - therapeutic use; Biological and Medical Applications of Materials and Interfaces; Cytokines - metabolism; Delayed-Action Preparations - chemistry; Indoles - chemistry; Methylprednisolone - pharmacokinetics; Methylprednisolone - therapeutic use; Microplastics - chemistry; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - etiology; Neuroinflammatory Diseases - metabolism; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Polymers - chemistry; Rats; Rats, Sprague-Dawley; Recovery of Function - drug effects; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord Injuries - complications; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - metabolism
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c11772

Neuroinflammation following spinal cord injury usually aggravates spinal cord damage. Many inflammatory cytokines are key players in neuroinflammation. Owing largely to the multiplicity of cytokine targets and the complexity of cytokine interactions, it is insufficient to suppress spinal cord damage progression by regulating only one or a few cytokines. Herein, we propose a two-pronged strategy to simultaneously capture the released cytokines and inhibit the synthesis of new ones in a broad-spectrum manner. To achieve this strategy, we designed a core/shell-structured microcomposite, which was composed of a methylprednisolone-incorporated polymer inner core and a biocompatible polydopamine outer shell. Thanks to the inherent adhesive nature of polydopamine, the obtained microcomposite (MP-PLGA@PDA) efficiently neutralized the excessive cytokines in a broad-spectrum manner within 1 day after spinal cord injury. Meanwhile, the controlled release of immunosuppressive methylprednisolone reduced the secretion of new inflammatory cytokines. Benefiting from its efficient and broad-spectrum capability in reducing the level of cytokines, this core/shell-structured microcomposite suppressed the recruitment of macrophages and protected the injured spinal cord, leading to an improved recovery of motor function. Overall, the designed microcomposite successfully achieved the two-pronged strategy in cytokine neutralization, providing an alternative approach to inhibit neuroinflammation in the injured spinal cord.