Biomimetic self-gelling and adhesive powder for seamless sealing and neural regeneration after brain injury

Abstract

Brain injury (BI) is often accompanied by dural rupture, cerebrospinal fluid (CSF) leakage combined with acute hemorrhage, which causes damage cascades that result in deterioration of the brain parenchyma. The simultaneous benefit of immediate long-lasting sealing and brain regeneration poses a great challenge in the clinical treatment of BI. Herein, a fully physically crosslinked bioactive sealing powder (BSP) is developed for surgical uses. BSP is a brain-mimicking, fast-gelling, and sprayable sealant composed of irregular grinding dispersions of collagen, azobenzene-functionalized hyaluronic acid and cyclodextrin-functionalized hyaluronic acid. Upon application to bleeding wounds, multiple host-guest interactions and physical assembly enable BSP to rapidly hydrate into viscoelastic hydrogel (within 10 s) with robust adhesion (13 kPa) and burst pressure (150 mmH₂O) to tissue. These features allow BSP to achieve rapid hemostatic effects in tail vein bleeding and liver injury models, and more importantly, the capacity of timely sealing of intestine defects and ruptured dura mater. In vivo evaluation on a rat BI model verified the safety and efficacy of BSP in preventing CSF leakage and thereby reducing inflammation. Specifically, BSP filling initiated endogenous cell recruitment, ensured neurogenesis and vascularization, facilitated brain structure remodeling and neural regeneration. This engineered biomaterial design, combining desirable attributes of easy-to-prepare and convenient-to-use in clinical application, offers new insights into sealing and repair integrated strategy for BI treatment. STATEMENT OF SIGNIFICANCE: It remains a significant challenge to develop a bioadhesive that can function as both a dural sealant and a regenerative substrate for brain injury (BI) treatment. Focusing on this, we engineered a selfgelling bioadhesive powder integrating collagen and functionalized hyaluronic acid derivatives. Harnessing host-guest interactions, BSP rapidly assembles upon blood contact, ensuring robust wet adhesion and high burst pressure to prevent hemorrhage and cerebrospinal fluid (CSF) leakage. Its brain-mimetic hydrogel forms a seamless dural seal while fostering endogenous neurogenesis. Clinically practical and easy to deploy, this strategy uniquely bridges effective hemostasis with neural regeneration, overcoming the limitations of existing biosealants in managing BI complications involving nerve damage and CSF leakage.

Keywords: Bioactive materials; Biomimetic; Brain injury repair; Hydrogel; Neural regeneration; Tissue regeneration.