Promotion of tendon healing by rosmarinic acid-based hydrogel

doi:10.3969/j.issn.1674-8115.2026.07.005

Abstract

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

CLC Number:

R318.08

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.

Figures/Tables 5

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

Fig 2 In vitro biocompatibility evaluation of the hydrogel

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

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

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

TrendMD

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