Biological therapies in tendon repair: Effects on functional recovery, structural integrity, and complication rates. A systematic review
DOI:
https://doi.org/10.58814/01208845.562Keywords:
Tendons, Therapy, Platelet-Rich Plasma, Mesenchymal Stem Cells, Acellular DermalAbstract
Introduction: Tendon injuries pose a significant clinical challenge due to limited regenerative capacity, resulting in incomplete healing, adhesions, and impaired function. Biological Therapies (BT), including Platelet-Rich Plasma (PRP), Mesenchymal Stem Cells (MSCs), Acellular Dermal Matrix (ADM), and Platelet Lysate (PL), have gained attention for their potential to enhance Tendon Repair (TR) through the modulation of inflammation, stimulation of angiogenesis, and promotion of collagen synthesis. However, the clinical outcomes of these therapies remain inconsistent.
Objective: To evaluate the current evidence on the use of these BT in TR, focusing on their efficacy in improving healing and functional outcomes, and their complications rate.
Methodology: This systematic review was conducted in accordance with the PRISMA 2020 guidelines. Comprehensive searches were conducted in October 2024 across PubMed, ScienceDirect and Google Scholar. Randomized controlled trials and observational studies assessing the efficacy of BTs in tendon repair and healing were included. Quality assessment was performed using the Cochrane RoB2 tool. Outcomes were synthesized focusing on functional recovery, structural integrity, and complication rates.
Results: PRP was the most studied therapy (66.6%, n=8), with mixed results. Chronic conditions such as lateral elbow tendinopathy showed significant long-term benefits (VAS reduction: -2.43; p<0.001). MSCs significantly improved functional scores in Achilles tendon ruptures (AOFAS: +15.8; p<0.01). ADM reduced postoperative adhesions and enhanced satisfaction (p<0.05). PL demonstrated superior long-term outcomes in rotator cuff tendinopathy (VAS: -2.5; p=0.01).
Conclusions: BTs show potential in TR, particularly in chronic conditions, but variability persists due to injury temporality, tendon-specific characteristics, and the biological therapy protocol employed. Standardization and combinatorial approaches may enhance clinical outcomes, warranting further high-quality research.
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References
1. Sakabe T, Sakai T. Musculoskeletal diseases--tendon. Br Med Bull. 2011;99(1):211–25. https://doi.org/10.1093/bmb/ldr025 PMID: 21729872; PMCID: PMC3202301.
2. Yang G, Rothrauff BB, Tuan RS. Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth Defects Res C Embryo Today. 2013;99(3):203–22. https://doi.org/10.1002/bdrc.21041 PMID: 24078497; PMCID: PMC4041869.
3. Kwan KYC, Ng KWK, Rao Y, Zhu C, Qi S, Tuan RS, Ker DFE, Wang DM. Effect of Aging on Tendon Biology, Biomechanics and Implications for Treatment Approaches. Int J Mol Sci. 2023;24(20):15183. https://doi.org/10.3390/ijms242015183 PMID: 37894875; PMCID: PMC101607611.
4. Graça AL, Gomez-Florit M, Gomes ME, Docheva D. Tendon aging. Subcell Biochem. 2023;103:121–47. https://doi.org/10.1007/978-3-031-26576-1_7 PMID: 37120467.
5. Feng H, Xing W, Han Y, Sun J, Kong M, Gao B, et al. Tendon-derived cathepsin K-expressing progenitor cells activate Hedgehog signaling to drive heterotopic ossification. J Clin Invest. 2020;130(12):6354–65. https://doi.org/10.1172/JCI132518 PMID: 32853181; PMCID: PMC7685727.
6. Zhang T, Wan L, Xiao H, Wang L, Hu J, Lu H. Single-cell RNA sequencing reveals cellular and molecular heterogeneity in fibrocartilaginous enthesis formation. Elife. 2023;12. https://doi.org/10.7554/eLife.85873 PMID: 37698466; PMCID: PMC10513478.
7. Frassanito P, Cavalieri C, Maestri R, Felicetti G. Effectiveness of Extracorporeal Shock Wave Therapy and kinesio taping in calcific tendinopathy of the shoulder: a randomized controlled trial. Eur J Phys Rehabil Med. 2018;54(3):333–40. https://doi.org/10.23736/S1973-9087.17.04749-9 PMID: 29185674.
8. Jaiswal D, Yousman L, Neary M, Fernschild E, Zolnoski B, Katebifar S, et al. Tendon tissue engineering: biomechanical considerations. Biomed Mater. 2020;15(5):052001. https://doi.org/10.1088/1748-605X/ab852f PMID: 32235051.
9. Docheva D, Müller SA, Majewski M, Evans CH. Biologics for tendon repair. Adv Drug Deliv Rev. 2015;84:222–39. https://doi.org/10.1016/j.addr.2014.11.015 PMID: 25446135; PMCID: PMC4519231.
10. DiIorio SE, Young B, Parker JB, Griffin MF, Longaker MT. Understanding Tendon Fibroblast Biology and Heterogeneity. Biomedicines. 2024;12(4):859. https://doi.org/10.3390/biomedicines12040859 PMID: 38672213; PMCID: PMC11048404.
11. Chen W, Sun Y, Gu X, Cai J, Liu X, Zhang X, et al. Conditioned medium of human bone marrow-derived stem cells promotes tendon-bone healing of the rotator cuff in a rat model. Biomaterials. 2021;271:120714. https://doi.org/10.1016/j.biomaterials.2021.120714 PMID: 33610048.
12. Cherief M, Xu J, Li Z, Tower RJ, Ramesh S, Qin Q, et al. TrkA-mediated sensory innervation of injured mouse tendon supports tendon sheath progenitor cell expansion and tendon repair. Sci Transl Med. 2023;15(727):eade4619. https://doi.org/10.1126/scitranslmed.ade4619 PMID: 38117901.
13. Darrieutort-Laffite C, Blanchard F, Soslowsky LJ, Le Goff B. Biology and physiology of tendon healing. Joint Bone Spine. 2024;91(5):105696. https://doi.org/10.1016/j.jbspin.2024.105696. PMID: 38307405.
14. Zhu J, Du Y, Backman LJ, Chen J, Ouyang H, Zhang W. Cellular Interactions and Biological Effects of Silk Fibroin: Implications for tissue engineering and regenerative medicine. Small. 2025;21(4):e2409739. https://doi.org/10.1002/smll.202409739 PMID: 39668424.
15. Chen JW, Galloway JL. Using the zebrafish to understand tendon development and repair. Methods Cell Biol. 2017;138:299–320. https://doi.org/10.1016/bs.mcb.2016.10.003 PMID: 28129848; PMCID: PMC5633932.
16. Li K, Deng Y, Deng G, Chen P, Wang Y, Wu H, et al. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells. Stem Cell Res Ther. 2020;11(1):131. https://doi.org/10.1186/s13287-020-01643-5 PMID: 32197645; PMCID: PMC70829
17. Zhu J, Du Y, Backman LJ, Chen J, Ouyang H, Zhang W. Cellular interactions and biological effects of silk fibroin: Implications for tissue engineering and regenerative medicine. Small. 2025;21(4):e2409739. https://doi.org/10.1002/smll.202409739 PMID: 39668424.
18. Steltzer SS, Abraham AC, Killian ML. Interfacial Tissue Regeneration with Bone. Curr Osteoporos Rep. 2024;22(2):290–8. https://doi.org/10.1007/s11914-024-00859-1 PMID: 38358401; PMCID: PMC110609
19. Nourissat G, Berenbaum F, Duprez D. Tendon injury: from biology to tendon repair. Nat Rev Rheumatol. 2015;11(4):223–33. https://doi.org/10.1038/nrrheum.2015.26 PMID: 257349
20. Silva M, Ferreira FN, Alves NM, Paiva MC. Biodegradable polymer nanocomposites for ligament/tendon tissue engineering. J Nanobiotechnology. 2020;18(1):23. https://doi.org/10.1186/s12951-019-0556-1 PMID: 32000800; PMCID: PMC6993465.
21. Sarmiento P, Little D. Tendon and multiomics: advantages, advances, and opportunities. NPJ Regen Med. 2021;6(1):61. https://doi.org/10.1038/s41536-021-00168-6 PMID: 34599188; PMCID: PMC84867
22. Sethi P, Fares MY, Murthi A, Tokish JM, Abboud JA. The long head of the biceps tendon: a valuable tool in shoulder surgery. J Shoulder Elbow Surg. 2023;32(9):1801–11. https://doi.org/10.1016/j.jse.2023.04.009 PMID: 37245621.
23. Padilla S, Sánchez M, Orive G, Anitua E. Human-based biological and biomimetic autologous therapies for musculoskeletal tissue regeneration. Trends Biotechnol. 2017;35(3):192–202. https://doi.org/10.1016/j.tibtech.2016.09.008 PMID: 280073
24. Kamble P, Prabhu RM, Jogani A, Mohanty SS, Panchal S, Dakhode S. Is Ultrasound (US)-Guided Platelet-Rich Plasma Injection More Efficacious as a Treatment Modality for Lateral Elbow Tendinopathy Than US-Guided Steroid Injection?: A Prospective Triple-Blinded Study with Midterm Follow-up. Clin Orthop Surg. 2023;15(3):454-462. https://doi.org/10.4055/cios22128 PMID: 37274509; PMCID: PMC10232317.
25. Vieira MHC, de Carvalho Schweich-Adami L, Oliveira RJ, Antoniolli-Silva ACMB. Effect of cell therapy with adipose-derived stem cells in the treatment of acute rupture of the Achilles tendon in humans. Cell Tissue Bank. 2024;25(3):831-838. https://doi.org/10.1007/s10561-024-10141-4 PMID: 38904737.
26. Haddaway NR, Page MJ, Pritchard CC, McGuinness LA. PRISMA2020: An R package and Shiny app for producing PRISMA 2020-compliant flow diagrams, with interactivity for optimised digital transparency and Open Synthesis. Campbell Syst Rev. 2022;18(2):e1230. https://doi.org/10.1002/cl2.1230 PMID: 36911350; PMCID: PMC8958186.
27. Moher D, Liberati A, Tetzlaff J, Altman DP; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. https://doi.org/10.1371/journal.pmed.1000097 PMID: 19621072; PMCID: PMC2707599.
28. Keene DJ, Alsousou J, Harrison P, O’Connor HM, Wagland S, Dutton SJ, Hulley P, Lamb SE, Willett K; PATH-2 Trial group. Platelet-rich plasma injection for acute Achilles tendon rupture: two-year follow-up of the PATH-2 randomized, placebo-controlled, superiority trial. Bone Joint J. 2022;104-B(11):1256-1265. https://doi.org/10.1302/0301-620X.104B11.BJJ-2022-0653.R1 PMID: 36317349; PMCID: PMC9621093.
29. Pitsilos C, Karachrysafi S, Fragou A, Gigis I, Papadopoulos P, Chalidis B. The Biological Effect of Platelet-Rich Plasma on Rotator Cuff Tears: A Prospective Randomized In Vivo Study. Int J Mol Sci. 2024;25(14):7957. https://doi.org/10.3390/ijms25147957 PMID: 39063199; PMCID: PMC112774
30. Centeno CJ, Fausel Z, Dodson E, Berger DR, Steinmetz NJ. Percutaneous bone marrow concentrate and platelet products versus exercise therapy for the treatment of rotator cuff tears: a randomized controlled, crossover trial with 2-year follow-up. BMC Musculoskelet Disord. 2024;25(1):392. https://doi.org/10.1186/s12891-024-07519-6 PMID: 38762734; PMCID: PMC111022
31. Thermann H, Fischer R, Gougoulias N, Cipollaro L, Maffulli N. Endoscopic debridement for non-insertional Achilles tendinopathy with and without platelet-rich plasma. J Sport Health Sci. 2023;12(2):275-80. https://doi.org/10.1016/j.jshs.2020.06.012 PMID: 32619656; PMCID: PMC10105028.
32. Markazi R, Soltani-Zangbar MS, Zamani M, Eghbal-Fard S, Motavalli R, Kamrani A, Dolati S, Ahmadi M, Aghebati-Maleki L, Mehdizadeh A, Eslamian F, Pishgahi A, Yousefi M. Platelet lysate and tendon healing: comparative analysis of autologous frozen-thawed PRP and ketorolac tromethamine in the treatment of patients with rotator cuff tendinopathy. Growth Factors. 2022;40(5-6):163-74. https://doi.org/10.1080/08977194.2022.2093198 PMID: 36026559.
33. Boesen AP, Boesen MI, Hansen R, Barfod KW, Lenskjold A, Malliaras P, Langberg H. Effect of Platelet-Rich Plasma on Nonsurgically Treated Acute Achilles Tendon Ruptures: A Randomized, Double-Blinded Prospective Study. Am J Sports Med. 2020;48(9):2268–76. https://doi.org/10.1177/0363546520922541 PMID: 32485112.
34. Rossi LA, Gorodischer TD, Camino P, Brandariz RN, Tanoira I, Piuzzi NS, Ranalletta M. Leukocyte-Poor Platelet-Rich Plasma as an Adjuvant to Arthroscopic Rotator Cuff Repair Reduces the Retear Rate But Does Not Improve Functional Outcomes: A Double-Blind Randomized Controlled Trial. Am J Sports Med. 2024;52(6):1403-1410. https://doi.org/10.1177/03635465241239062 PMID: 38587033.
35. Lee YJ, Ryoo HJ, Shim HS. Prevention of postoperative adhesions after flexor tendon repair with acellular dermal matrix in Zones III, IV, and V of the hand: A randomized controlled (CONSORT-compliant) trial. Medicine (Baltimore). 2022;101(3):e28630. https://doi.org/10.1097/MD.0000000000028630 PMID: 35060544; PMCID: PMC8772763.
36. Zhang C, Cai Y-Z, Wang Y. Injection of leukocyte-poor platelet-rich plasma for moderate-to-large rotator cuff tears does not improve clinical outcomes but reduces retear rates and fatty infiltration: A prospective, single-blinded randomized study. Arthroscopy. 2022;38(8):2381-2388.e1. https://doi.org/10.1016/j.arthro.2022.02.007 PMID: 35247512.
37. Olesen JL, Hansen M, Turtumoygard IF, Hoffner R, Schjerling P, Christensen J, et al. No treatment benefits of local administration of insulin-like growth factor-1 in addition to heavy slow resistance training in tendinopathic human patellar tendons: A randomized, double-blind, placebo-controlled trial with 1-year follow-up. Am J Sports Med. 2021;49(9):2361–70. https://doi.org/10.1177/03635465211021056 PMID: 34138667.
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