Epigallocatechin-3-Gallate (EGCG)-Loaded Hyaluronic Acid Hydrogel Seems to Be Effective in a Rat Model of Collagenase-Induced Achilles Tendinopathy

Overview

Journal J Funct Biomater

Specialty Biomedical Engineering

Date 2025 Feb 25

PMID 39997589

Authors

Hwa Jun Kang

Sivakumar Allur Subramanian

Si Young Song

Jihyun Hwang

Collin Lee

Sung Jae Kim

Affiliations

Soon will be listed here.

Abstract

Tendon injuries account for 45% of musculoskeletal injuries. However, research on the occurrence and pathogenesis of tendinopathy is insufficient, and there is still much debate regarding treatment methods. It is important to understand the molecular mechanisms of oxidative stress and inflammatory responses because oxidative stress in tendon tissue is induced by various factors, including inflammatory cytokines, drug exposure, and metabolic abnormalities. In this study, 28 rats were divided into four groups (7 rats assigned to each group): control group (CON), collagenase injection group (CL), collagenase injection and hyaluronic acid injection group (CL + HA), and collagenase injection and EGCG-loaded hyaluronic acid injection group (CL + HA + EGCG). Seven weeks after the start of the study, all rats underwent histochemical analysis, immunofluorescence staining, and Western blot. The results showed increased inflammatory cells, disarray of collagen matrix, and degradation of the collagen matrix in the CL group. However, in the EGCG-treated group, there was a significant increase in type I collagen expression and a significant decrease in type III collagen expression, compared to the CL group. Additionally, there was an increase in the expression of antioxidant markers SOD (Superoxide Dismutase) and CAT (Catalase), tenogenic markers COLL-1 (collagen type I), and SCX (Scleraxis), and a downregulated expression of apoptosis markers cas-3 and cas-7. Our findings suggest that EGCG-loaded hyaluronic acid hydrogel exhibits potential in preventing tendon damage and promoting the regeneration process in a rat model of Achilles tendinopathy. The insights gained from our histological and molecular investigations highlight the future potential for testing novel tendinopathy treatments in human subjects.

References

Rho J, Ko I, Jin J, Hwang L, Kim S, Chung J . Polydeoxyribonucleotide Ameliorates Inflammation and Apoptosis in Achilles Tendon-Injury Rats. Int Neurourol J. 2020; 24(Suppl 2):79-87. PMC: 7731881. DOI: 10.5213/inj.2040428.214. View

Yoshimoto Y, Takimoto A, Watanabe H, Hiraki Y, Kondoh G, Shukunami C . Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system. Sci Rep. 2017; 7:45010. PMC: 5361204. DOI: 10.1038/srep45010. View

Feng H, He Z, Twomey K, Ilaltdinov A, Leong D, Wang Y . Epigallocatechin-3-gallate suppresses pain-related and proinflammatory mediators in the subacromial bursa in rotator cuff tendinopathy. Discov Med. 2019; 27(147):63-77. View

Semis H, Gur C, Ileriturk M, Kandemir F, Kaynar O . Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases. Am J Sports Med. 2021; 50(2):486-498. DOI: 10.1177/03635465211059821. View

Hsieh Y, Lin M, Hong C, Chen H . Percutaneous soft tissue release performed using a blunt cannula in rabbits with chronic collagenase-induced Achilles tendinopathy. Foot Ankle Surg. 2018; 25(2):186-192. DOI: 10.1016/j.fas.2017.10.007. View

Yun H, Yoo W, Han M, Lee Y, Kim J, Lee S . Epigallocatechin-3-gallate suppresses TNF-alpha -induced production of MMP-1 and -3 in rheumatoid arthritis synovial fibroblasts. Rheumatol Int. 2008; 29(1):23-9. DOI: 10.1007/s00296-008-0597-5. View

Sharma P, Maffulli N . Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact. 2006; 6(2):181-90. View

Annaniemi J, Pere J, Giordano S . Platelet-rich plasma versus corticosteroid injections for rotator cuff tendinopathy: a comparative study with up to 18-month follow-up. Clin Shoulder Elb. 2022; 25(1):28-35. PMC: 8907507. DOI: 10.5397/cise.2021.00486. View

Moore N, Pollack C, Butkerait P . Adverse drug reactions and drug-drug interactions with over-the-counter NSAIDs. Ther Clin Risk Manag. 2015; 11:1061-75. PMC: 4508078. DOI: 10.2147/TCRM.S79135. View

10.

Maffulli N, Spiezia F, Longo U, Denaro V, Maffulli G . High volume image guided injections for the management of chronic tendinopathy of the main body of the Achilles tendon. Phys Ther Sport. 2012; 14(3):163-7. DOI: 10.1016/j.ptsp.2012.07.002. View

11.

Hildebrand K, Jia F, Woo S . Response of donor and recipient cells after transplantation of cells to the ligament and tendon. Microsc Res Tech. 2002; 58(1):34-8. DOI: 10.1002/jemt.10114. View

12.

Magra M, Maffulli N . Nonsteroidal antiinflammatory drugs in tendinopathy: friend or foe. Clin J Sport Med. 2005; 16(1):1-3. DOI: 10.1097/01.jsm.0000194764.27819.5d. View

13.

Maffulli N, Reaper J, Ewen S, Waterston S, Barrass V . Chondral metaplasia in calcific insertional tendinopathy of the Achilles tendon. Clin J Sport Med. 2006; 16(4):329-34. DOI: 10.1097/00042752-200607000-00008. View

14.

Hsiao M, Lin A, Liao W, Wang T, Hsu C, Chen W . Drug-loaded hyaluronic acid hydrogel as a sustained-release regimen with dual effects in early intervention of tendinopathy. Sci Rep. 2019; 9(1):4784. PMC: 6423120. DOI: 10.1038/s41598-019-41410-y. View

15.

Wang H, Guo Y, Jiang Y, Ge Y, Wang H, Shi D . Exosome-loaded biomaterials for tendon/ligament repair. Biomater Transl. 2024; 5(2):129-143. PMC: 11438604. DOI: 10.12336/biomatertransl.2024.02.004. View

16.

Gonzalez-Alfonso J, Penalver P, Ballesteros A, Morales J, Plou F . Effect of α-Glucosylation on the Stability, Antioxidant Properties, Toxicity, and Neuroprotective Activity of (-)-Epigallocatechin Gallate. Front Nutr. 2019; 6:30. PMC: 6438877. DOI: 10.3389/fnut.2019.00030. View

17.

Mi C, Qi X, Ding Y, Zhou J, Dao J, Wei D . Recent advances of medical polyhydroxyalkanoates in musculoskeletal system. Biomater Transl. 2024; 4(4):234-247. PMC: 10817797. DOI: 10.12336/biomatertransl.2023.04.004. View

18.

Li X, Su Z, Shen K, Wang Q, Xu C, Wang F . Eugenol-Preconditioned Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Antioxidant Capacity of Tendon Stem Cells and . Oxid Med Cell Longev. 2022; 2022:3945195. PMC: 8847013. DOI: 10.1155/2022/3945195. View

19.

Staal J, de Bie R, de Vet H, Hildebrandt J, Nelemans P . Injection therapy for subacute and chronic low back pain: an updated Cochrane review. Spine (Phila Pa 1976). 2009; 34(1):49-59. DOI: 10.1097/BRS.0b013e3181909558. View

20.

Cetik R, Yabanoglu Ciftci S, Arica B, Baysal I, Dizakar S, Elibol F . Evaluation of the Effects of Transforming Growth Factor-Beta 3 (TGF-β3) Loaded Nanoparticles on Healing in a Rat Achilles Tendon Injury Model. Am J Sports Med. 2022; 50(4):1066-1077. DOI: 10.1177/03635465211073148. View