全球健康难题脓毒症，因宿主免疫失衡引发器官衰竭，病死率居高不下。传统疗法难以解决免疫麻痹与继发感染难题，而近期发表于 Materials Today Bio 的重磅研究，构建了β-葡聚糖糖肽水凝胶递送系统，通过招募并训练巨噬细胞逆转免疫麻痹，为脓毒症治疗开辟全新路径。研究中，Absin 组织解离液（abs9482）成为关键支撑工具，助力精准解析局部免疫重塑机制。

一、研究核心思路：从"急救"到"长效防御"的脓毒症新策略

脓毒症治疗的核心痛点：急性期炎症风暴 + 恢复期免疫麻痹，传统方案顾此失彼。

本研究创新设计双功能糖肽水凝胶 BGA@t-RADA16：

• 氧化 β-葡聚糖（BGA）：经典训练免疫诱导剂，激活巨噬细胞获得免疫记忆
• 巨噬靶向肽 t-RADA16：精准招募巨噬，形成局部"训练免疫中心"
• 可注射自组装水凝胶：缓释 BGA，避免全身炎症风险，实现靶向-缓释-应答级联治疗
• 加载多黏菌素 B（BGA-P@t-RADA16）：急性期杀菌 + 长期免疫训练双效合一

二、重磅研究成果：水凝胶重塑免疫，大幅提升脓毒症生存率

1. 材料构建：可注射、自修复的糖肽水凝胶（原文 Fig.1）

• 氧化 β-葡聚糖（BGA）与 t-RADA16 通过希夫碱交联，形成β-折叠纳米纤维网络
• 流变证实：剪切变稀 + 快速自修复，完美适配皮下注射
• 缓释优势：BGA 在体内滞留超 72h，游离 BGA 12h 即被清除（原文 Fig.4A-B）

Fig. 1.
Preparation and characterization of hydrogel BGA@t-RADA16. (A) Schematic diagram of preparation of BGA@t-RADA16. (B) Representative pictures of BGA@t-RADA16 manufacturing process. (C) Representative SEM images of BGA, t-RADA16 and BGA@t-RADA16. (D) Representative TEM images of BGA, t-RADA16 and BGA@t-RADA16. Rheology of BGA@t-RADA16 as a function of angular frequency (E) CD spectrum of BGA@t-RADA16. (F, G) Rheological analysis of BGA@t-RADA16 as a function of angular frequency (F) and shear strain (G). (H) The self-healing analysis of BGA@t-RADA16 with an alternative large oscillation force (50%) and a small one (2%).

2. 体外机制：强效训练巨噬，增强吞噬与炎症应答（原文 Fig.2）

• BGA@t-RADA16 显著提升 IL-1β/IL-6/TNF-α 分泌，促 M1 型极化
• 细菌吞噬能力较游离 BGA 提升1.5 倍，较对照组提升4.8 倍
• 转录 + 代谢组证实：激活 TLR/NF-κB 通路，重塑糖脂代谢，奠定训练免疫基础（原文 Fig.3）

Fig. 2.
BGA@t-RADA16 mediates trained immunity of BMDMs in vitro. (A) Schematic of in vitro trained immunity experimental setup. The production of (B) IL-1β (C) IL-6 and (D) TNF-α by BMDMs trained with BG and BGA was measured by ELISA after 4 h of LPS treatment. (E, F) Determination of M1 type macrophages (CD11b+ F4/80+ CD80+ subgroup) in each group by flow cytometry. The production of (G) IL-1β (H) IL-6 and (I) TNF-α by BMDMs trained with BGA@t-RADA16 was measured by ELISA after 4 h of LPS treatment. (J, K) Determination of M1 type macrophages (CD11b+ F4/80+ CD80+ subgroup) in each group by flow cytometry. (L, M) The phagocytosis of BMDMs in each group was measured by confocal microscopy. Data are shown as mean ± SEM (n = 3). ns: no significant difference, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Fig. 3.
Transcriptomic and metabolomic characteristics of BMDMs after BGA@t-RADA16 training. (A) Differentially expressed genes (DEGs) in control group vs. BGA@t-RADA16 group. (B) DEGs summarized between the BGA@t-RADA16-trained group, the BGA-trained group and the control group. (C) Heatmap comparison of GO enrichment analysis results (p < 0.05) among BGA@t-RADA16-trained groups. (D) Heatmap comparison of gene set enrichment analysis (GSEA) results (p < 0.05) among BGA@t-RADA16-trained groups. NES, Normalized enrichment score. (E) Volcano map of the DMs. (F) PCA plot of the qualitative metabolite changes. (G) Heatmap of pooled DMs between BGA@t-RADA16-trained groups and control group. (H) KEGG enrichment results of DMs.

3. 体内疗效：逆转免疫麻痹，降低病死率至 30%

• 免疫麻痹小鼠模型：提升腹腔单核/巨噬比例，减轻肺肝损伤，抵御大肠杆菌感染（原文 Fig.5）
• CLP 脓毒症模型：BGA-P@t-RADA16 组病死率从 80% 降至 30%，优于临床激素 + 抗生素方案（原文 Fig.6G）
• 继发感染保护：训练免疫依赖巨噬细胞，显著降低细菌载量，激活 CD8+T 细胞（原文 Fig.7）

Fig. 5.
Effect of BGA@t-RADA16 on preventing sepsis in immunoparalysis mice. (A) Schematic diagram of establishing an in vivo immunoparalysis model and inducing trained immunity. Proportion of peritoneal (B, C) monocytes, (D, E) macrophages, (F, G) M1 macrophages and (H, I) M2 macrophages after different treatments. The content of (J) IL-1β, (K) IL-6 and (L) TNF-α in serum was measured by ELISA after different treatment. (M) Representative images of H&E staining of the liver and lungs of mice after different treatment. In the PBS, E.coli, t-RADA16 and BGA groups, inflammatory cell infiltration and consequent organ damage were observed at the locations marked by arrowheads. Data are shown as mean ± SEM (n = 3). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Fig. 7.
BGA-P@t-RADA16 induces monocyte/macrophage trained immunity and protects against secondary infection after sepsis. (A) Schematic diagram of establishing the CLP model caused by cecum ligation and puncture and its treatment. Proportion of peritoneal (B, F) CCR2+ myeloid cells, (C, G) monocytes, (D, H) M1 macrophages and spleen (E, I) CD8+ T cells after 24 h of the last treatment. The content of (J) IL-6 and (K) TNF-α in serum was measured by ELISA after 12 h of secondary infection. Mouse blood and peritoneal lavage fluid were taken after 2 h of secondary infection for 16 h of bacterial culture showed statistical graphs of the number of colonies in (L) blood and (M) peritoneal lavage fluid. Data are shown as mean ± SEM. ns: no significant difference, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

三、Absin 核心贡献：abs9482 解锁组织免疫细胞精准分析

本研究在注射部位局部巨噬招募与表型分析（原文 Fig.4C-I）关键环节，使用Absin 组织解离液 abs9482，成为数据可靠的核心保障：

abs9482 凭借多组织适配、高细胞活率、抗原友好特性，已成为免疫、肿瘤、类器官等领域单细胞研究的标配工具，支撑多项高分研究发表。

四、研究意义与转化前景

本研究首次实现β-葡聚糖 + 自组装肽的脓毒症免疫训练递送，构建预防-急救-长效防御一体化方案：

• 突破游离 β-葡聚糖清除快、易致全身炎症的瓶颈
• 单系统实现急性期杀菌 + 慢性期免疫重启，解决脓毒症免疫失衡
• 可注射水凝胶临床转化潜力大，为免疫麻痹相关疾病提供通用平台

五、Absin 助力生命科学，持续赋能前沿研究

Absin 始终以高品质试剂支撑顶尖科研，abs9482 组织解离液等产品已助力全球学者发表超 1200 篇高水平论文。未来，Absin 将继续深耕免疫治疗、材料生物学等领域，为科研工作者提供更可靠的工具，加速基础研究向临床转化。