摘要：当“补气之长”黄芪遇见“通经活络”的牛膝，在纳米实验室里碰撞出了怎样的火花？国家纳米科学中心韩东研究员团队创造性地开发出一种负载具有载药能力的牛膝超自组装体的新型复合水凝胶。3天内将伤口收缩率提升至51.81%，14天实现功能性皮肤再生！这一“源于自然，优于自

导读：当“补气之长”黄芪遇见“通经活络”的牛膝，在纳米实验室里碰撞出了怎样的火花？国家纳米科学中心韩东研究员团队创造性地开发出一种负载具有载药能力的牛膝超自组装体的新型复合水凝胶。3天内将伤口收缩率提升至51.81%，14天实现功能性皮肤再生！这一“源于自然，优于自然”的设计，调节了伤口免疫微环境，为伤口治疗提供了极具前景的新策略。

伤口愈合的难题与天然材料的机遇

皮肤伤口愈合是一个复杂而精密的生物学过程，涉及止血、炎症、增殖和重塑四个阶段。其中，炎症微环境的调控是愈合的关键。若炎症反应失衡，M1型巨噬细胞会持续分泌TNF-α、IL-6，伤口陷入“高炎泥潭”。同时，新生血管不足，胶原沉积紊乱，导致愈合延迟、纤维化甚至形成难看的疤痕。现有水凝胶敷料多依赖合成材料（如PEG、PLGA），虽具生物相容性，却缺乏主动调控微环境的能力。此外，中药的自组装已成为近年来的热门研究课题。特别是在皮肤修复材料的研究中，中药衍生的自组装体显示出更多的生物相容性和活性优势，这种自组装特性在牛膝提取物中得到完美印证。

二、中药宝库的技术突破

1. 牛膝超自组装体及其“天然药匣”功能

• 发现：牛膝（Achyranthes bidentata）提取物在特定工艺下，自发形成微米级球形自组装体（NX SSA），直径约1.87±0.57 μm（图1F）；

• 载药创新：将疏水性姜黄素（Cur）嵌入NX SSA疏水内核，形成NX@Cur“中药胶囊”，成功抑制姜黄素结晶（XRD衍射峰消失，图1E），粒径增至2.69±0.54 μm。

2. 黄芪多糖的免疫调节功效

• 黄芪多糖（APS）经氧化修饰（OAPS），通过Schiff碱动态交联与紫外光共价交联构建双网络（图2A）；

• 赋予水凝胶基质固有抗炎能力：下调炎症因子iNOS，促进M2型巨噬细胞转化。

Figure 1. Fabrication and Characterization of NX@Cur. (A) Schematic diagram of NX@Cur preparation. (B) Potential values before and after drug loading. (C) Infrared spectra of NX, Cur, and NX@Cur. (D) UV spectra of NX, Cur, and NX@Cur. (E) X-ray diffraction patterns of NX, Cur, and NX@Cur. (F) Scanning electron micrographs of NX, Cur, and NX@Cur. (Scale bar: 5 μm.) (G) Particle size distribution statistics of NX and NX@Cur. (H) Transmission electron micrographs and electron diffraction patterns of NX, Cur, and NX@Cur. Data are reported as means ± SD (*p

三、“双剑合璧”载药水凝胶设计：可注射+光固化+药物分级缓释

团队创新设计OCS/NX@Cur双网络水凝胶递药系统（Scheme 1）：

Scheme 1. Illustration of a Natural Polysaccharide Hydrogel Loaded with NX@Cur for Wound Repair

1. 可注射初阶凝胶：OAPS+CMC+SAMA+Mg²⁺混合形成动态交联网络，像“液体绷带”贴合于不规则伤口（图2C）；紫外光固化粘合组织：365 nm光照触发共价交联，粘附强度达20.94 kPa（图2F）。

2 . 药物分级缓释：释放周期延长至240小时（常规载体仅48小时），精准匹配愈合周期。

Figure 2. Preparation and properties of OCS and OCS/NX@Cur hydrogels. (A) Schematic diagram of the preparation of the OCS/NX@Cur hydrogel. (B) Scanning electron micrographs of OCS and OCS/NX@Cur hydrogels. (C) Demonstration of the injectability of the hydrogel and optical images of the two gelation stages. (D) Hydrogels being adhered to organs or skin. (E) Photographs of hydrogels adhered to skin being bent or twisted and stretched. (F) Shear force–distance curves of hydrogels adhered to pig skin. (G) Viscosity–shear rate curves of OCSUC and OCS hydrogels. (H) Modulus–angular frequency curves of OCSUC and OCS hydrogels. (I) Compressive strength–strain curves of OCS and OCS/NX@Cur hydrogels. (J) Dissolution rates of OCS and OCS/NX@Cur hydrogels at different times. (K) Degradation rates of OCS and OCS/NX@Cur hydrogels at different times. (L) Curves of drug release from Cur, NX@Cur, and OCS/NX@Cur. Data are reported as means ± SD (*p

四、三重复合功效：抗炎+促血管生成+胶原重塑

1. 伤口收缩率显著提升（第3天OCS/NX@Cur组达51.81%，图6）；H&E染色显示的新生毛囊结构（图7 A绿色箭头），标志皮肤全层功能性再生；OCS/NX@Cur组的马松染色切片中显示出更多的有序胶原（图7）

2 . 免疫失衡逆转：OCS/NX@Cur组M2/M1比例提升13.42倍（相比于对照组）；OCS/NX@Cur组的炎症因子骤降，其中TNF-α↓59.29%，IL-6↓77.75%（图9）

3 . 血管网络重建：OCS/NX@Cur组CD31标记血管密度提升89%（图9E）

4 . 胶原有序重塑：胶原I/III比例提升至1.74（对照组仅0.22），接近健康皮肤水平（图8）

Figure 6. Wound repair results of the OCS/NX@Cur hydrogel system. (A) Schematic diagram of the establishment and treatment of the whole layer skin defect model. (B) Representative pictures of wounds at different time points. Wound imaging using a standard metal positioning ring (15 mm inner diameter), the edge of which provides a dimensional reference. (Scale bar: 5 mm) (C) Area map of the wound over time. (D) Wound shrinkage rates of different treatment regimens at different time points. Data are reported as means ± SD (*p

Figure 7. Histologic analysis. (A) H&E staining of the wound tissue on day 7 and day 14. (Scale bar: 200 μm) (B) Masson staining of wound tissues on day 7 and day 14. (Scale bar: 200 μm).

Figure 8. Collagen type analysis. (A) Images of wound tissue on day 7 and day 14 stained with Sirius red under bright field and polarized light microscopy. (Scale bar: 500 μm) (B) Quantification of type III collagen in wound tissue on days 7 and 14. (C) Quantification of type I collagen in wound tissue on day 7 and 14. Data are reported as means ± SD (*p

Figure 9. Immunomodulatory and neovascularization capacity of the OCS/NX@Cur hydrogel system. (A) Representative images of immunofluorescence staining for iNOS and CD206 in wound tissue on day 7. (Scale bar: 100 μm) (B) Average fluorescence intensity of iNOS and CD206 expression in immunofluorescence staining results. (C) Relative values of M2/M1 expression in immunofluorescence staining results. (D) Semiquantitative analysis of the relative coverage area of CD31 expression in immunohistochemical staining results. (E) Representative images of CD31 immunohistochemical staining of wound tissue on day 7 (Scale bar: 100 μm). Data are reported as means ± SD (*p

五、核心创新点

1. 为中药现代化提供纳米科技新范式，首创中药自组装载体NX SSA，破解姜黄素递送难题

2. 多功能协同的天然多糖水凝胶药物递送平台：以具有抗炎活性的黄芪多糖为骨架构建的OCS水凝胶，不仅提供了良好的理化性质，其本身也是积极的治疗参与者

3 . 级联治疗机制：“免疫调节→血管重建→胶原重塑”三重协同

4 . 良好的细胞、血液相容性和体内安全性，蕴含巨大应用潜力

六、展望：中医理论与纳米技术的跨界融合

千年药匣中或隐藏着下一代生物材料的密码本！这项研究不仅为全层皮肤缺损伤口提供治疗方案，更启示中药超自组装技术的巨大潜力：

• 载体库拓展：挖掘更多具自组装特性的本草（如三七多糖等）

• 智能化升级：开发智能响应型中药敷料，精准调控释药动力学

正如团队所言：中药复杂成分具有自组装的内在特性，我们将挖掘更多本草资源，利用其自组装潜能构建智能递药库。

来源：高分子科学前沿