Positively Charged Polyurethane Scaffolds Reshape the Microenvironment to Promote Endogenous Regeneration after Brain Injury

Traumatic brain injury (TBI) induces a prolonged inflammatory response throughout the damaged brain, which is exacerbated by the sustained accumulation of damage-associated molecular patterns (DAMPs), and consequently impairs endogenous neural regeneration significantly. To mitigate postinjury inflammation and explore the role of positively charged scaffolds in brain repair, two distinct structures of positively charged scaffolds were developed. Both scaffold types effectively reduce inflammation and promote brain tissue repair by eliminating DAMPs, markedly reducing glial scar formation, and promoting angiogenesis in peritrauma areas within 4 weeks of implantation. Notably, scaffolds with cationic backbones exhibit repair outcomes superior to those of other groups due to reduced cellular stimulation and milder chronic inflammation. This study underscores the potential of positively charged scaffolds for central nervous system (CNS) regeneration and provides novel insights into the design of tissue engineering scaffolds for CNS repair.