迷迭香酸基水凝胶的促肌腱愈合效应

doi:10.3969/j.issn.1674-8115.2026.07.005

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (7): 868-874.doi: 10.3969/j.issn.1674-8115.2026.07.005

• 论著 · 基础研究 • 上一篇

迷迭香酸基水凝胶的促肌腱愈合效应

王缘¹, 吴容浦¹, 王非²(), 刘珅¹()

^1.上海交通大学医学院附属第六人民医院骨科，上海 200233
^2.上海交通大学医学院附属瑞金医院上海市伤骨科研究所/上海市中西医结合防治骨与关节病损重点实验室，上海 200025

收稿日期:2026-03-17 接受日期:2026-04-13 出版日期:2026-07-10 发布日期:2026-07-10
通讯作者: 刘　珅，主任医师，教授，博士；电子信箱：liushensjtu@sjtu.edu.cn。
王　非，副研究员，博士；电子信箱：wangfeirj@163.com。
基金资助:
国家重点研发计划(2024YFC2418105);国家自然科学基金(82572709);上海交通大学医学院“双百人”项目(20191829)

Promotion of tendon healing by rosmarinic acid-based hydrogel

Wang Yuan¹, Wu Rongpu¹, Wang Fei²(), Liu Shen¹()

^1.Department of Orthopedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
^2.Shanghai Institute of Traumatology and Orthopedics/Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Traditional Chinese and Western Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received:2026-03-17 Accepted:2026-04-13 Online:2026-07-10 Published:2026-07-10
Contact: Liu Shen, E-mail: liushensjtu@sjtu.edu.cn.
Wang Fei, E-mail: wangfeirj@163.com. ^#Co-corresponding authors.
Supported by:
National Key Research and Development Program of China(2024YFC2418105);National Natural Science Foundation of China(82572709);“Two-hundred Talents”Program of Shanghai Jiao Tong University School of Medicine(20191829)

摘要/Abstract

摘要：

目的·构建一种负载迷迭香酸（rosmarinic acid，RA）的水凝胶，并研究其在促进跟腱损伤后组织修复及功能恢复中的作用。方法·苯硼酸与羧甲基壳聚糖经酰胺化反应，制备得到苯硼酸修饰的羧甲基壳聚糖（phenylboronic acid-modified carboxymethyl chitosan，CMCS-PBA），通过核磁共振氢谱（¹H nuclear magnetic resonance，¹H-NMR）表征CMCS-PBA的分子结构。将CMCS-PBA与RA按照体积比10∶1混合制备CMCS-PBA/RA水凝胶；另将CMCS-PBA与聚乙烯醇（polyvinyl alcohol，PVA）混合制备CMCS-PBA/PVA水凝胶，作为阳性对照。通过流变仪对其流变学性能、自愈合能力及力学性能进行系统表征。选用大鼠成纤维细胞系208F，通过活/死细胞染色评估水凝胶的生物相容性。选用18只大鼠，构建大鼠跟腱横断模型后随机分为3组（每组6只），即对照组、CMCS-PBA/RA组和CMCS-PBA/PVA组。建模结束后，CMCS-PBA/RA与CMCS-PBA/PVA组即刻在断裂肌腱处注射对应水凝胶，完全覆盖损伤部位，对照组不做水凝胶干预。饲养3周后处死大鼠，取材后行苏木精-伊红（hematoxylin and eosin，HE）染色、Masson染色，评估肌腱愈合情况；通过步态分析检测跟腱功能恢复情况。取大鼠主要脏器，行HE染色，进一步评价水凝胶体内生物相容性。结果·¹H-NMR结果证实PBA成功接枝至CMCS分子链。流变测试表明，制备所得水凝胶具备良好的剪切稀化、自愈合与可注射性性能。活/死细胞染色及脏器HE染色结果证实该水凝胶生物相容性良好。与对照组和CMCS-PBA/PVA组相比，CMCS-PBA/RA组跟腱愈合评分更低（均P<0.05），跟腱愈合效果更佳。步态分析显示，CMCS-PBA/RA组足印面积显著增大（均P<0.05），肢体功能恢复更优。结论·成功制备CMCS-PBA与RA组成的新型水凝胶。该水凝胶具有良好的可注射性、自愈合性能及生物相容性，能够有效促进跟腱组织修复与运动功能恢复。

关键词: 迷迭香酸, 水凝胶, 肌腱损伤, 肌腱修复, 可注射, 自愈合

Abstract:

Objective ·To construct a rosmarinic acid (RA)-loaded hydrogel and investigate its effects on tissue repair and functional recovery after Achilles tendon injury. Methods ·Phenylboronic acid-modified carboxymethyl chitosan (CMCS-PBA) was synthesized via an amidation reaction between phenylboronic acid and carboxymethyl chitosan, and the molecular structure of CMCS-PBA was confirmed by ¹H nuclear magnetic resonance (¹H-NMR) spectroscopy. CMCS-PBA/RA hydrogel was prepared by mixing CMCS-PBA with RA at a volume ratio of 10∶1. CMCS-PBA/PVA hydrogel composed of CMCS-PBA and polyvinyl alcohol (PVA) served as the positive control. The rheological property, self-healing ability, and mechanical performance of the hydrogel were systematically characterized with a rheometer. Rat fibroblast cell line 208F was used to evaluate the biocompatibility of the hydrogels via live/dead cell staining. Eighteen rats with established Achilles tendon transection models were randomly assigned into three groups (n=6 per group): the control group, the CMCS-PBA/RA group, and the CMCS-PBA/PVA group. In the CMCS-PBA/RA and CMCS-PBA/PVA groups, the corresponding hydrogels were locally injected into the injured tendons immediately after model establishment to completely cover the injury site, while no hydrogel intervention was administered in the control group. All rats were sacrificed 3 weeks postoperatively. Hematoxylin-eosin (HE) staining and Masson staining were performed to evaluate tendon healing, and gait analysis was conducted to assess functional recovery. Major visceral organs were harvested for HE staining to further verify the in vivo biocompatibility of the prepared hydrogels. Results ·¹H-NMR results confirmed the successful grafting of PBA onto the CMCS molecular chains. Rheological characterization demonstrated that the prepared hydrogels possessed excellent shear-thinning behavior, self-healing ability, and favorable injectability. Live/dead staining and organ HE staining verified the favorable biocompatibility of the hydrogels. Compared with the control and CMCS-PBA/PVA groups, the CMCS-PBA/RA group exhibited significantly lower tendon healing scores (both P<0.05), indicating superior tendon healing. Gait analysis showed a significantly larger footprint area in the CMCS-PBA/RA group (both P<0.05), which reflected better functional recovery. Conclusion ·A novel CMCS-PBA/RA composite hydrogel was successfully prepared. The hydrogel possesses excellent injectability, self-healing capability, and biocompatibility, and effectively promotes Achilles tendon tissue repair and motor functional recovery.

Key words: rosmarinic acid, hydrogel, tendon injury, tendon repair, injectability, self-healing

中图分类号:

R318.08

王缘, 吴容浦, 王非, 刘珅. 迷迭香酸基水凝胶的促肌腱愈合效应[J]. 上海交通大学学报（医学版）, 2026, 46(7): 868-874.

Wang Yuan, Wu Rongpu, Wang Fei, Liu Shen. Promotion of tendon healing by rosmarinic acid-based hydrogel[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(7): 868-874.

图/表 5

图1 CMCS-PBA/RA水凝胶的构建及其流变学与自愈合性能表征Note： A. Schematic illustration of CMCS-PBA synthesis. B. ¹H-NMR characterization of CMCS-PBA. C. Schematic illustration of hydrogel formation. D. Strain-dependent rheological properties of the hydrogel. The variations of G′ and G″ with strain demonstrate the structural integrity and deformation tolerance of the network. E. Thixotropic behavior of the CMCS-PBA/RA hydrogel under alternating shear strains (5% and 500%). F. Self-healing behavior of the hydrogel. Representative photographs of the hydrogel before and after self-healing. The hydrogel was cut into two pieces and subsequently brought into contact for 1 min at room temperature to allow spontaneous healing.

Fig 1 Construction, rheological properties and self-healing performance of the CMCS-PBA/RA hydrogel

图2 水凝胶的体外生物相容性评价Note： A. Live/dead cell staining, with green indicating live cells and red indicating dead cells. B. Quantification of cell death rate.

Fig 2 In vitro biocompatibility evaluation of the hydrogel

图3 大鼠跟腱横断模型的构建及手术过程示意图Note： A. Disinfection of the right hind limb. B. Achilles tendon exposure. C. Kessler suture and tendon transection. D. Wound closure.

Fig 3 Construction and surgical procedure of the rat Achilles tendon transection model

图4 CMCS-PBA/RA水凝胶促进肌腱愈合及功能恢复的体内效果评价Note： A. HE staining (n=6). B. Masson′s trichrome staining (n=6). C. Tendon healing score (n=6). D. Footprint area in gait analysis (n=6).

Fig 4 In vivo evaluation of the CMCS-PBA/RA hydrogel for promoting tendon healing and functional recovery

图5 水凝胶干预3周后大鼠主要组织器官HE染色结果（ n=3）

Fig 5 HE staining of major organs in rats after 3 weeks of hydrogel intervention (n=3)

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迷迭香酸基水凝胶的促肌腱愈合效应

Promotion of tendon healing by rosmarinic acid-based hydrogel

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