Repetitive or excessive loading, abnormal extension of the tendon tissue, or the fracture of the tendon might be a trigger tendinopathy induction5. Tendinopathy or enthesopathy is a complex condition characterized by molecular, histological, and cellular changes appearing in affected tendons and nearby structures that leads to persistent, pain, swelling, and impaired physical performance6. This condition can be also characterized by ineffective neovasularisation, decreased collagen I, and enhance collagen II production7. Moreover, alongside the physical tendon damage, the response of the cells to the pathological stimuli is increased inflammation, together with the release of pro-catabolic molecules, like cytokines and chemokines and tissue degradation enzymes8.
HA during the tendinopathy and enthesopathy
The implementation of the HA during the tendinopathy connects with a vast beneficial outcome. HA is involved in the tissue repair process regulation and tendon healing modulation, such as inflammation or cellular migration9. Furthermore, the implementation of the HA during the tendinopathy leads to decrease of the peripheral inflammatory response and promotes healing via tendon cells, in both repair site and synovial sheath3. It is proven that administration of HA inhibits the proliferation of fibroblasts and due to its anti-inflammatory actions, stimulates the synthesis of the endogenous HA in the tendons10.
HA vs Corticosteroids in tendinopathy and enthesopathy
HA intratendinous or peritendinous injections were proven to be clinically more efficient and safer than corticosteroid (CS) administration. This is based on the fact that despite CS’s broad use, its safety is put into serious consideration11. Scientific evidence shows that CS may influence tendon homeostasis, by disorganization of a collagen structure, which will lead to tenocyte viability reduction and increase in possibility of future tendon rupture8. Literature points out that CS decreases the fibroblasts proliferation rate and delays the healing of the tendon structure. This suggests that CS injection might disturb the early phases of tendon repair, regeneration and remodeling compared to HA12,13.
Mechanism of HA action in tendon
- HA helps to establish homeostasis in tendon environment
- HA acts as anti-inflammatory agent after tendon rupture14
- HA with optimally high MW bind to CD44 receptors with further receptor clustering, which trigger the anti-inflammatory, wound healing, anti-angiogenic, and immunosuppressive actions3,15
- HA inhibits tissue degradation processes by decreasing the matrix metalloproteinase (MMP) release16
- HA promotes mechanisms of tendon repair by increases tenocytes viability and type I collagen production and deposition2
- Kogan G, Šoltés L, Stern R, Gemeiner P. Hyaluronic acid: a natural biopolymer with a broad range of biomedical and industrial applications. Biotechnol Lett. 2006;29(1):17-25. doi:10.1007/s10529-006-9219-z
- Aicale R, Tarantino D, Maffulli N. Non-insertional Achilles Tendinopathy: State of the Art. In: Canata GL, d’Hooghe P, Hunt KJ, Kerkhoffs GMMJ, Longo UG, eds. Sports Injuries of the Foot and Ankle. Springer Berlin Heidelberg; 2019:359-367. doi:10.1007/978-3-662-58704-1_32
- Oliva F, Marsilio E, Asparago G, Frizziero A, Berardi AC, Maffulli N. The Impact of Hyaluronic Acid on Tendon Physiology and Its Clinical Application in Tendinopathies. Cells. 2021;10(11):3081. doi:10.3390/cells10113081
- Hagberg L, Heinegård D, Ohlsson K. The Contents of Macromolecule Solutes in Flexor Tendon Sheath Fluid and Their Relation to Synovial Fluid: A quantitative analysis. Journal of Hand Surgery. 1992;17(2):167-171. doi:10.1016/0266-7681(92)90081-C
- Kaux JF, Forthomme B, Goff CL, Crielaard JM, Croisier JL. Current opinions on tendinopathy. J Sports Sci Med. 2011;10(2):238-253.
- Millar NL, Silbernagel KG, Thorborg K, et al. Tendinopathy. Nat Rev Dis Primers. 2021;7(1):1. doi:10.1038/s41572-020-00234-1
- Frizziero A, Oliva F, Vittadini F, et al. Efficacy of ultrasound-guided hyaluronic acid injections in achilles and patellar tendinopathies:a prospective multicentric clinical trial. Muscle Ligaments and Tendons J. 2019;09(03):305. doi:10.32098/mltj.03.2019.01
- Crimaldi S, Liguori S, Tamburrino P, et al. The Role of Hyaluronic Acid in Sport-Related Tendinopathies: A Narrative Review. Medicina. 2021;57(10):1088. doi:10.3390/medicina57101088
- Litwiniuk M, Krejner A. Hyaluronic Acid in Inflammation and Tissue Regeneration. 2016;28(3).
- Ozgenel GY, Etoz A. Effects of repetitive injections of hyaluronic acid on peritendinous adhesions after flexor tendon repair: a preliminary randomized, placebo-controlled clinical trial. Ulus Travma Acil Cerrahi Derg. 2012;18(1):11-17. doi:10.5505/tjtes.2012.95530
- Dean BJF, Lostis E, Oakley T, Rombach I, Morrey ME, Carr AJ. The risks and benefits of glucocorticoid treatment for tendinopathy: A systematic review of the effects of local glucocorticoid on tendon. Seminars in Arthritis and Rheumatism. 2014;43(4):570-576. doi:10.1016/j.semarthrit.2013.08.006
- Nakamura H, Gotoh M, Kanazawa T, et al. Effects of corticosteroids and hyaluronic acid on torn rotator cuff tendons in vitro and in rats: CS/HA EFFECTS ON RCTs. J Orthop Res. 2015;33(10):1523-1530. doi:10.1002/jor.22921
- Lu H, Yang H, Shen H, Ye G, Lin XJ. The clinical effect of tendon repair for tendon spontaneous rupture after corticosteroid injection in hands: A retrospective observational study. Medicine. 2016;95(41):e5145. doi:10.1097/MD.0000000000005145
- Kaux JF, Samson A, Crielaard JM. Hyaluronic acid and tendon lesions. Muscles Ligaments Tendons J. 2015;5(4):264-269. doi:10.11138/mltj/2015.5.4.264
- Wu PT, Kuo LC, Su FC, et al. High-molecular-weight hyaluronic acid attenuated matrix metalloproteinase-1 and -3 expression via CD44 in tendinopathy. Sci Rep. 2017;7(1):40840. doi:10.1038/srep40840
- Wu PT, Su WR, Li CL, et al. Inhibition of CD44 induces apoptosis, inflammation, and matrix metalloproteinase expression in tendinopathy. Journal of Biological Chemistry. 2019;294(52):20177-20184. doi:10.1074/jbc.RA119.009675