Abstract: BACKGROUND: The regeneration and remodeling of Achilles tendon rupture after surgery are difficulties in clinical treatment. Tissue engineering hydrogels afford the possibility on the healing of postoperative Achilles tendon.
OBJECTIVE: To investigate the effect of tannic acid modified interpenetrating network hydrogel on tissue regeneration and remodeling of ruptured Achilles tendon in rats.
METHODS: (1) The interpenetrating network hydrogel was prepared under the blue light and the immersion of CaSO4 solution. The micromorphology, mechanical properties, adhesion properties, in vitro drug release properties, and biocompatibility of hydrogels were characterized. (2) Thirty Sprague-Dawley rats were randomly divided into sham operation group, operation group, and hydrogel group, with 10 rats in each group. The animal model of Achilles tendon rupture was established in the latter two groups. In the operation group, the ruptured Achilles tendon was sutured using the modified Kessler method. In the hydrogel group, the ruptured Achilles tendon was repaired by the same method, and the tannic acid modified interpenetrating network hydrogel patch was completely wrapped around the joint of the broken end. Four weeks after the operation, imaging examination, histological evaluation, biomechanical test, and the level test of inflammatory factors were performed. 
RESULTS AND CONCLUSION: (1) Scanning electron microscope showed that tannic acid modified interpenetrating network hydrogels had porous microstructure with pore size of 3-10 μm, and the hydrogels had good in vitro drug release properties, adhesion strength and tensile strength. CCK-8 assay and live/dead staining showed that the hydrogel had no significant effect on the proliferation activity of rat bone marrow mesenchymal stem cells, and had good biocompatibility. (2) MRI imaging showed that compared with the operation group, the Achilles tendon in the hydrogel group showed uniform low signal, the thickness of the anteroposterior diameter of the Achilles tendon was reduced, and the boundary between the Achilles tendon and the surrounding tissue was more clear, and the performance was more similar to that of the sham operation group. Hematoxylin-eosin staining and Masson staining showed that the tendon fibers in the operation group were arranged in a loose and chaotic manner, with increased cell density and disordered arrangement, accompanied by obvious inflammatory cell infiltration, and intratendinous ossification appeared in some areas. In the hydrogel group, the tendon fibers were arranged in an orderly manner; the cell density was reduced and arranged orderly; the inflammatory cell infiltration was significantly reduced. The tensile strength of Achilles tendon in the operation group was lower than that in the sham operation group (P < 0.05). The tensile strength of Achilles tendon in the hydrogel group was higher than that in the operation group (P < 0.05). Compared with sham operation group, the mass concentration and mRNA expression of interleukin-1β, interleukin-6, and tumor necrosis factor α in Achilles tendon of rats were increased in the operation group (P < 0.05). Compared with the operation group, the level and mRNA expression of three inflammatory factors were decreased in the hydrogel group. (3) It is concluded that tannic acid modified interpenetrating network hydrogel can inhibit the local inflammatory response and promote the tendon remodeling.

Key words: tannic acid, hydrogel, interpenetrating network, Achilles tendon rupture, tissue remodeling, tissue regeneration