Effect of Hyaluronic Acid on Rabbit Profundus Flexor Tendon Healing in Vitro

Rotator cuff tears (RCTs) and rotator cuff disease (RCD) are important causes of disability in middle-aged individuals affected by nontraumatic shoulder dysfunctions. Our previous studies have demonstrated that four different hyaluronic acid preparations (HAPs), including Artrosulfur® hyaluronic acid (HA) (Alfakjn S.r.l., Garlasco, Italy), may exert a protective effect in human RCT-derived tendon cells undergoing oxidative stress damage. Recently, methylsulfonylmethane (MSM) (Barentz, Paderno Dugnano, Italy) has proven to have anti-inflammatory properties and to cause pain relief in patients affected by tendinopathies. This study aims at evaluating three preparations (Artrosulfur® HA, MSM, and Artrosulfur® MSM + HA) in the recovery from hydrogen peroxide-induced oxidative stress damage in human tenocyte. Cell proliferation, Lactate Dehydrogenase (LDH) release, and inducible nitric oxide synthases (iNOS) and prostaglandin E2 (PGE2) modulation were investigated. In parallel, expression of metalloproteinases 2 (MMP2) and 14 (MMP14) and collagen types I and III were also examined. Results demonstrate that Artrosulfur® MSM + HA improves cell escape from oxidative stress by decreasing cytotoxicity and by reducing iNOS and PGE2 secretion. Furthermore, it differentially modulates MMP2 and MMP14 levels and enhances collagen III expression after 24 h, proteins globally related to rapid acceleration of the extracellular matrix (ECM) remodelling and thus tendon healing. By improving the anti-cytotoxic effect of HA, the supplementation of MSM may represent a feasible strategy to ameliorate cuff tendinopathies.

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Gene Expression Analysis of the Pleiotropic Effects of TGF-β1 in an In Vitro Model of Flexor Tendon Healing

PLoS ONE ◽

10.1371/journal.pone.0051411 ◽

2012 ◽

Vol 7 (12) ◽

pp. e51411 ◽

Cited By ~ 46

Author(s):

Youssef M. Farhat ◽

Alaa A. Al-Maliki ◽

Tony Chen ◽

Subhash C. Juneja ◽

Edward M. Schwarz ◽

...

Keyword(s):

Gene Expression ◽

Expression Analysis ◽

Gene Expression Analysis ◽

In Vitro Model ◽

Flexor Tendon ◽

Tendon Healing ◽

Pleiotropic Effects ◽

Vitro Model ◽

Tgf Β1

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Carbodiimide-Derivatized Hyaluronic Acid Surface Modification of Lyophilized Flexor Tendon: A Biomechanical Study in a Canine in Vitro Model

Yearbook of Hand and Upper Limb Surgery ◽

10.1016/j.yhls.2011.03.007 ◽

2011 ◽

Vol 2011 ◽

pp. 53-54

Author(s):

J.B. Tang

Keyword(s):

Surface Modification ◽

Hyaluronic Acid ◽

In Vitro Model ◽

Flexor Tendon ◽

Biomechanical Study ◽

Vitro Model

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Hyaluronic acid diminishes the resistance to excursion after flexor tendon repair: An in vitro biomechanical study

Journal of Biomechanics ◽

10.1016/j.jbiomech.2004.04.021 ◽

2005 ◽

Vol 38 (3) ◽

pp. 503-507 ◽

Cited By ~ 33

Author(s):

T. Akasaka ◽

J. Nishida ◽

S. Araki ◽

T. Shimamura ◽

P.C. Amadio ◽

...

Keyword(s):

Hyaluronic Acid ◽

Flexor Tendon ◽

Tendon Repair ◽

Biomechanical Study ◽

Flexor Tendon Repair

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Hyaluronic Acid Modulates Cell Proliferation Unequally in Intrasynovial and Extrasynovial Rabbit Tendons In Vitro

Journal of Hand Surgery (European Volume) ◽

10.1054/jhsb.1999.0354 ◽

2000 ◽

Vol 25 (2) ◽

pp. 183-187 ◽

Cited By ~ 16

Author(s):

M. WIIG ◽

S.-O. ABRAHAMSSON

Keyword(s):

Cell Proliferation ◽

Hyaluronic Acid ◽

Mechanism Of Action ◽

Biochemical Composition ◽

Matched Control ◽

Flexor Tendon ◽

Acid Sensitivity ◽

Collagen Protein ◽

Matrix Components

As tendons differ in biochemical composition and cellular capacities, we have compared dose response effects of hyaluronic acid on cell proliferation and synthesis of matrix components in intermediate and proximal segments of intrasynovial deep flexor tendons and extrasynovial peroneus rabbit tendons in vitro. Compared with matched control tendons, hyaluronic acid inhibited cell proliferation in intermediate and proximal intrasynovial flexor tendon segments at the concentrations of 0.1–2.0 mg/ml and 0.5–2.0 mg/ml respectively, but in extrasynovial tendon segments only at the concentration of 0.5 mg/ml. Hyaluronic acid did not affect synthesis of proteoglycan, collagen and non-collagen protein in either type of tendon. These results show that hyaluronic acid modulates cell proliferation unequally in intra- and extrasynovial tendons without affecting the synthesis of matrix components in the two types of tendons, indicating differential hyaluronic acid sensitivity and a possible mechanism of action.

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The Impact of Hyaluronic Acid on Tendon Physiology and Its Clinical Application in Tendinopathies

Cells ◽

10.3390/cells10113081 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3081

Author(s):

Francesco Oliva ◽

Emanuela Marsilio ◽

Giovanni Asparago ◽

Antonio Frizziero ◽

Anna Concetta Berardi ◽

...

Keyword(s):

Molecular Weight ◽

Hyaluronic Acid ◽

Clinical Application ◽

Chemical Properties ◽

Tendon Healing ◽

Biological Properties ◽

Patellar Tendinopathy ◽

Physical Chemical ◽

The Impact

The physical–chemical, structural, hydrodynamic, and biological properties of hyaluronic acid within tendons are still poorly investigated. Medical history and clinical applications of hyaluronic acid for tendinopathies are still debated. In general, the properties of hyaluronic acid depend on several factors including molecular weight. Several preclinical and clinical experiences show a good efficacy and safety profile of hyaluronic acid, despite the absence of consensus in the literature regarding the classification according to molecular weight. In in vitro and preclinical studies, hyaluronic acid has shown physical–chemical properties, such as biocompatibility, mucoadhesivity, hygroscopicity, and viscoelasticity, useful to contribute to tendon healing. Additionally, in clinical studies, hyaluronic acid has been used with promising results in different tendinopathies. In this narrative review, findings encourage the clinical application of HA in tendinopathies such as rotator cuff, epicondylitis, Achilles, and patellar tendinopathy.

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