In situ delivery of cannabidiol-loaded GelMA sponge attenuates cerebral edema and neuroinflammation in traumatic brain injury.

Authors

Hengxi Li, Xinyuan Luo, Yan Cao, Hongyan Jiang, Zhiying Guo, Yiwei Zhu, Leyu Zhang, Zixin Li, Jinglin Li, Haiying Wu, Ping Li

Published in

Materials today. Bio. Volume 41. Pages 103721. Epub Oct 01, 2026.

Abstract

Traumatic brain injury (TBI) remains a major cause of severe disability, and its secondary injury remains a key focus of interventional research. Cannabidiol (CBD) has neuroprotective potential, but conventional systemic administration still has limitations. In this study, we fabricated an in situ-implantable cannabidiol-loaded gelatin methacryloyl (GelMA) sponge (GM-CBD) with short-term cytocompatibility and hemocompatibility and no detectable in vivo abnormalities. Under a non-equivalent dosing regimen, GM-CBD and intraperitoneally injected CBD (10 mg/kg) showed distinct concentration-distribution profiles: in the GM-CBD group, CBD continuously accumulated in the perilesional cortex over 48 h, whereas serum CBD remained persistently low. In a rat Feeney model of TBI, combined behavioral and neuropathological evaluation identified a single sponge loaded with a nominal 15 μg CBD as the working dose. At this dose, GM-CBD reduced neurological deficit scores, altered locomotor and exploratory behaviors in TBI rats, and attenuated neuronal injury and apoptosis. GM-CBD concurrently upregulated tight junction proteins and CD31⁺ endothelial cell expression, downregulated GFAP⁺ astrocyte proliferation, and altered AQP4 distribution, thereby improving blood-brain barrier integrity and alleviating post-traumatic cerebral edema. Furthermore, GM-CBD decreased IL-6, IL-1β, and TNF-α levels, increased IL-10, and inhibited microglial activation, suggesting attenuated acute neuroinflammation after TBI. Transcriptomic sequencing further showed that GM-CBD-associated differentially expressed genes were mainly involved in immune, stress, and inflammatory responses, with significant enrichment of the NF-κB, PI3K-Akt, and TNF signaling pathways. In summary, GM-CBD provides an in situ sustained-release strategy that exerts neuroprotection by attenuating post-traumatic cerebral edema and neuroinflammation.

PMID:
42891034
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

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