Polydopamine nanoparticle-enhanced stem cell spheroid-derived decellularized extracellular matrix with antioxidant...

The use of implantable biomaterials has emerged as a promising therapeutic strategy for managing traumatic brain injury (TBI). We have previously demonstrated that mesenchymal stem cell (MSC) spheroid-derived three-dimensional decellularized extracellular matrix (3D dECM), enriched with stem cell secretome, serves as an effective biomaterial for promoting post-TBI brain repair. However, its limited antioxidant capacity and inadequate tissue adhesion remain significant challenges. To overcome these limitations, in the present study, we functionalized 3D dECM with polydopamine nanoparticles (PDANPs), renowned for their inherent antioxidant and adhesive properties, to enhance free radical scavenging and tissue adhesion. PDANP decoration imparted significant reactive oxygen/reactive nitrogen species-scavenging capacity to 3D dECM, thereby enhancing its neuroprotective potential and reducing oxidative stress-induced neuronal cell death in vitro. In a mouse TBI model, PDANP-decorated 3D dECM demonstrated robust adhesion to cortical tissues, effectively addressing post-TBI secondary injury by mitigating oxidative damage and suppressing neuroinflammation, ultimately promoting neuronal cell survival. The adhesive, antioxidant, and immunomodulatory properties together led to improved recovery of neurological function and reduced lesion volume in vivo. Overall, our findings highlight the potential of PDANP-decorated 3D dECM as a multifunctional and clinically translatable therapeutic platform for TBI management, while underscoring the adaptability of MSC spheroid-derived 3D dECM to be precisely tailored for diverse therapeutic applications.