Hyaluronic Acid Treatment Improves Healing of the Tenorrhaphy Site by Suppressing Adhesions through Extracellular Matrix Remodeling in a Rat Model

Kwang Hyeon Ahn,Eun Soo Park,Chang Yong Choi,Han Gyu Cha,Seung Min Nam,Yongsung Hwang

doi:10.3390/polym13060928

Abstract

Due to the limited supply of vessels and nerves, acute or chronic tendon injuries often result in significant and persistent complications, such as pain and sprains, as well as the loss of joint functions. Among these complications, tendon adhesions within the surrounding soft tissue have been shown to significantly impair the range of motion. In this study, to elucidate the effects of a hyaluronic acid (HA) injection at the site of tenorrhaphy on tendon adhesion formation, we used a full transection model of a rat’s Achilles tendon to investigate the anti-adhesive function of HA. Our initial findings showed that significantly lower adhesion scores were observed in the HA-treated experimental group than in the normal saline-treated control group, as determined by macroscopic and histological evaluations. Hematoxylin and eosin, as well as picrosirius red staining, showed denser and irregular collagen fibers, with the larger number of infiltrating inflammatory cells in the control group indicating severe adhesion formation. Furthermore, we observed that the expression of tendon adhesion markers in operated tendon tissue, such as collagen type I, transforming growth factor-β1, and plasminogen activator inhibitor-1, was suppressed at both the gene and protein levels following HA treatment. These results suggest that HA injections could reduce tendon adhesion formation by significantly ameliorating inflammatory-associated reactions.

Highlights

Due to the limited supply of vessels and nerves, acute or chronic tendon injuries of the hand often result in significant pain and sprains, as well as the loss of joint mobility and stability in patients [1,2]
At 10 weeks following surgery, the Achilles tendon tissues were examined using hematoxylin and eosin (H&E) and picrosirius red staining to evaluate the degree of adhesion and tendon recovery after tenorrhaphy (Figure 2A–D)
In the hyaluronic acid (HA) group, no adhesion formation was observed in 33.3% of tendons, slight adhesion formation in 41.8% of tendons, and moderate adhesion formation in 24.9% of tendons

Summary

Introduction

Due to the limited supply of vessels and nerves, acute or chronic tendon injuries of the hand often result in significant pain and sprains, as well as the loss of joint mobility and stability in patients [1,2]. The most significant and persistent complication of these injuries is tendon adhesion, which leads to problems in joint flexion and contracture, occurring in approximately 30–40% of both repaired and unrepaired cases [3,4]. Fibroblasts in native tissues migrate from the surrounding tissue to the injured end of the tendon, leading to adhesion formation between the tendon and the surrounding tissue [6]. To overcome this severe post-operative complication, various attempts have been made to prevent tendon adhesion formation [7,8]. There has been tremendous interest in the development of anti-adhesive agents for the suppression of adhesion formation between tendons and the surrounding connective tissue [11]

Methods

Results

Discussion

Conclusion