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

Li H.; Luo X.; Cao Y.; Jiang H.; Guo Z.; Zhu Y.; Zhang L.; Li Z.; Li J.; Wu H. et al. · Materials today. Bio · 2026

**Background & Methods** This experimental study evaluated an in situ-implantable cannabidiol-loaded gelatin methacryloyl (GelMA) sponge (GM-CBD) in a rat Feeney model of traumatic brain injury (TBI). The sponge was compared to intraperitoneal CBD injection (10 mg/kg) for efficacy in reducing secondary brain injury through behavioral assessment, neuropathological evaluation, and transcriptomic analysis. **Key Findings** • GM-CBD achieved sustained CBD delivery directly to perilesional cortex over 48 hours with persistently low serum levels, contrasting with systemic distribution from intraperitoneal administration. A single sponge loaded with 15 μg CBD reduced neurological deficits, improved locomotor and exploratory behaviors, and decreased neuronal injury and apoptosis in TBI rats. • GM-CBD improved blood-brain barrier integrity by upregulating tight junction proteins and CD31+ endothelial cells, downregulating GFAP+ astrocyte proliferation, and normalizing AQP4 distribution, resulting in attenuation of post-traumatic cerebral edema. • GM-CBD suppressed acute neuroinflammation by reducing pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), increasing anti-inflammatory IL-10, and inhibiting microglial activation. Transcriptomic analysis identified differentially expressed genes primarily involved in immune and inflammatory responses, with enrichment in NF-κB, PI3K-Akt, and TNF signaling pathways. **Dosage & Administration** A single implanted GelMA sponge containing 15 μg CBD was identified as the optimal working dose. This contrasted with intraperitoneally injected CBD at 10 mg/kg, demonstrating substantially different pharmacokinetic profiles despite non-equivalent dosing regimens. **Safety & Adverse Effects** The GM-CBD sponge demonstrated short-term cytocompatibility and hemocompatibility with no detectable in vivo abnormalities reported. **Evidence Quality** This is a preclinical animal study (rat model) with significant limitations for human translation. The study lacks long-term follow-up data beyond 48 hours, uses a single animal model, and does not report detailed mechanistic pathways. Publication year (2026) suggests this may be a projected or in-press manuscript. As a preclinical investigation, it provides low-to-moderate evidence quality (Level 3-4) and requires substantial human clinical validation before therapeutic application.

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