A tannic acid/bioactive peptide co-assembled hydrogel for constructing a neural regeneration niche in traumatic brain injury repair

• TA@SPG was synthesized by pH-responsive co-assembly of tannic acid and Fmoc-DIKVAV. • Tannic acid modification strengthened hydrogel reassembly after high strain. • TA@SPG promoted neural stem cell adhesion and differentiation into neurons. • TA@SPG cleared ROS and inhibited inflammation after traumatic brain injury. Neuronal regenerative impairment following traumatic brain injury (TBI) is a critical clinical challenge. Engineering a regeneration-permissive neural niche therefore stands as a novel therapeutic strategy. In this study, a tannic acid (TA)-integrated self-assembling peptide hydrogel (TA@SPG) was developed through a TA-induced, pH-responsive co-assembly process between Fmoc-DIKVAV and TA, with the aim of synergistically scavenging harmful factors and providing structural support for neural stem cell (NSC)-mediated neuronal regeneration. This simple method allowed for the integration of TA into the hydrogel through non-covalent TA-peptide interactions, which also slowed the hydrogel’s degradation. Biological evaluation demonstrated that TA@SPG improved the tissue microenvironment at the brain injury site by modulating microglial polarization from a pro-inflammatory to an anti-inflammatory phenotype and scavenging excess reactive oxygen species (ROS). Furthermore, TA@SPG exhibited excellent adhesion to NSCs and promoted their differentiation into mature neurons. This dual support for neurogenesis reduced brain tissue defects and enhanced neurological function recovery after TBI. This study provides a promising therapeutic strategy for neuronal regeneration after TBI.