Surgical‐Adjuvant Hydrogel of Full‐Natural Bioactive Compounds from Chinese Medicine for Enhanced Traumatic Brain Injury Therapy by Inhibiting Complement Activation

Abstract Complement activation drives inflammatory cascades that exacerbate secondary injuries in both acute traumatic brain injury (TBI) and postsurgical complications, yet remains clinically unaddressed by timely interventions. Here, a surgical‐adjuvant hydrogel platform (AG‐gel) is engineered through molecular self‐assembly strategy, utilizing fully natural bioactive components from Chinese medicine to enable early phase complement activation modulation. AG‐gel is self‐assembled from natural bioactive constituents (amygdalin and glycyrrhizic acid) under physiological conditions, demonstrating injectability and intrinsic pharmacological functions. With a single application after TBI debridement, AG‐gel shows efficacy in improving neurological function in preclinical TBI models. Specifically, AG‐gel achieves synergistic suppression of complement system activation through a dual mechanism that combines blood–brain barrier preservation to block peripheral C3 infiltration and directly binds to the C3 , thereby disrupting the self‐amplifying neuroinflammatory loop driven by glial activation crosstalk while potentiating endogenous neuroprotection. Collectively, this work provides an alternative surgical‐adjuvant hydrogel strategy for complement activation in TBI and related surgical manipulation.