A Self‐Gelling Powder Directly Co‐Assembled by Natural Small Molecules for Traumatic Brain Injury

Abstract The prognosis for traumatic brain injury (TBI) depends largely on prompt hemostasis and effective pharmacologic interventions. Natural all‐small‐molecule self‐gelling powder, integrating the advantages of self‐assembled small‐molecule hydrogels and powders, is expected to provide timely and effective prehospital management of TBI. However, the synthesis and application of natural all‐small‐molecule self‐gelling powder is still uncharted territory. In this study, an all‐small‐molecule co‐assembled MGF‐H₃BO₃‐RUT (MBR) self‐gelling powder is fabricated through the co‐assembly of mangiferin (MGF) and rutin (RUT) in H₃BO₃/NaOH aqueous solution. Both compounds can bind with boric acid, leading to co‐assembling into hydrogels through hydrogen‐bonding interactions and π–π stacking. MBR self‐gelling powder is then obtained by drying the as‐prepared hydrogels, thus integrating hemostasis and pharmacodynamics into one. Remarkably, it displays robust regeneration capabilities, while retaining excellent self‐healing properties and injectability after drying‐hydration cycles. Moreover, MBR self‐gelling powder not only achieves rapid effective hemostasis but also attenuates conspicuously cerebral edema and inflammatory response after TBI by in situ spraying, exhibiting notable neuroprotective effects without discernible toxic side effects. This study provides a novel assembly strategy and application form for self‐assembled gel materials originating from natural small molecules, offering promising avenues for the treatment of TBI in the acute phase.