REGENERATIVE STRATEGIES FOR SPORTS-RELATED MUSCULOSKELETAL INJURIES: FROM PRP TO 3D BIOPRINTING
DOI:
https://doi.org/10.31435/ijitss.1(49).2026.5330Keywords:
Regenerative Medicine, Sports Injuries, Platelet-Rich Plasma, Mesenchymal Stem Cells, Rehabilitation, Return-to-PlayAbstract
Regenerative medicine is becoming an increasingly important part of sports medicine, especially in the treatment of musculoskeletal injuries that are difficult to manage with conventional methods alone. This review provides a structured and clinically focused overview of established and emerging regenerative therapies used in sports-related musculoskeletal conditions. Particular attention is given to platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), exosome-based therapies, low-intensity pulsed ultrasound (LIPUS), hydrogel-based scaffolds, bone marrow aspirate concentrate, adipose-derived biologics, and three-dimensional (3D) bioprinting. A structured narrative review with scoping characteristics was conducted in accordance with PRISMA-ScR recommendations. Articles published between 2003 and 2025 were identified through PubMed, Scopus, Web of Science, and Google Scholar, with priority given to studies relevant to clinical practice, rehabilitation, functional outcomes, and athlete-centered recovery. The reviewed evidence suggests that PRP and MSC-based therapies currently represent the main biologic approaches in this field, while newer technologies offer promising but still largely experimental directions for future treatment. The value of regenerative therapies extends beyond tissue repair alone and may also influence rehabilitation, return-to-play, and quality of life. At the same time, their clinical use remains limited by methodological heterogeneity, lack of standardization, and insufficient long-term data. Further high-quality studies are needed to define clear indications, improve treatment protocols, and support the evidence-based integration of regenerative therapies into modern sports medicine.
References
Andia, I., & Maffulli, N. (2013). Platelet-rich plasma for muscle injury and tendinopathy. Sports Medicine and Arthroscopy Review, 21(4), 191–198. https://doi.org/10.1097/JSA.0b013e318299972b
Andia, I., & Maffulli, N. (2017). Biological therapies in regenerative sports medicine. Sports Medicine, 47(5), 807–828. https://doi.org/10.1007/s40279-016-0620-z
Ardern, C. L., Glasgow, P., Schneiders, A., Witvrouw, E., Clarsen, B., Cools, A., Gojanovic, B., Griffin, S., Khan, K. M., Moksnes, H., Mutch, S. A., Phillips, N., Reurink, G., Sadler, R., Silbernagel, K. G., Thorborg, K., Wangensteen, A., Wilk, K. E., & Bizzini, M. (2016). 2016 consensus statement on return to sport from the First World Congress in Sports Physical Therapy, Bern. British Journal of Sports Medicine, 50(14), 853–864. https://doi.org/10.1136/bjsports-2016-096278
Ardern, C. L., Taylor, N. F., Feller, J. A., & Webster, K. E. (2013). Psychological responses to sports injury. British Journal of Sports Medicine, 47, 112–118. https://doi.org/10.1177/0363546513489284
Ardern, C. L., Webster, K. E., Taylor, N. F., & Feller, J. A. (2011). Return to sport following anterior cruciate ligament reconstruction surgery: A systematic review and meta-analysis of the state of play. British Journal of Sports Medicine, 45(7), 596–606. https://doi.org/10.1136/bjsm.2010.076364
Bahr, R., & Krosshaug, T. (2005). Understanding injury mechanisms: A key component of preventing injuries in sport. British Journal of Sports Medicine, 39(6), 324–329. https://doi.org/10.1136/bjsm.2005.018341
Blair, P., & Flaumenhaft, R. (2009). Platelet α-granules: Basic biology and clinical correlates. Blood Reviews, 23, 177–189. https://doi.org/10.1016/j.blre.2009.04.001
Brewer, B. W., Andersen, M. B., & Van Raalte, J. L. (2002). Psychological aspects of sport injury rehabilitation: Toward a biopsychosocial approach. In D. L. Mostofsky & L. D. Zaichkowsky (Eds.), Medical and psychological aspects of sport and exercise (pp. 41–54). Fitness Information Technology.
Caplan, A. I. (2007). Adult mesenchymal stem cells for tissue engineering versus regenerative medicine. Journal of Cellular Physiology, 213(2), 341–347. https://doi.org/10.1002/jcp.21200
Caplan, A. I., & Correa, D. (2011). The MSC: An injury drugstore. Cell Stem Cell, 9(1), 11–15. https://doi.org/10.1016/j.stem.2011.06.008
Cavallo, C., Roffi, A., Grigolo, B., Mariani, E., Pratelli, L., Merli, G., Kon, E., Marcacci, M., & Filardo, G. (2016). Platelet-rich plasma: The choice of activation method affects the release of bioactive molecules. BioMed Research International, 2016, Article 6591717. https://doi.org/10.1155/2016/6591717
Cerza, F., Carnì, S., Carcangiu, A., Di Vavo, I., Schiavilla, V., Pecora, A., De Biasi, G., & Ciuffreda, M. (2012). Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. The American Journal of Sports Medicine, 40(12), 2822–2827. https://doi.org/10.1177/0363546512461902
Chen, J., Zhou, R., Feng, Y., & Cheng, L. (2022). Molecular mechanisms of exercise contributing to tissue regeneration. Signal Transduction and Targeted Therapy, 7(1), 383. https://doi.org/10.1038/s41392-022-01233-2
Chen, Y., Yang, H., Wang, Z., Zhu, R., Cheng, L., & Cheng, Q. (2023). Low-intensity pulsed ultrasound promotes mesenchymal stem cell transplantation-based articular cartilage regeneration via inhibiting the TNF signaling pathway. Stem Cell Research & Therapy, 14(1), 93. https://doi.org/10.1186/s13287-023-03296-6
Cheng, M., Wang, H., Yoshida, R., & Murray, M. M. (2010). Platelets and plasma proteins are both required to stimulate collagen gene expression by anterior cruciate ligament cells in three-dimensional culture. Tissue Engineering Part A, 16(5), 1479–1489. https://doi.org/10.1089/ten.TEA.2009.0199
Choi, J. R., Yong, K. W., & Choi, J. Y. (2018). Effects of mechanical loading on human mesenchymal stem cells for cartilage tissue engineering. Journal of Cellular Physiology, 233(3), 1913–1928. https://doi.org/10.1002/jcp.26018
Clarke, L. E., McConnell, J. C., Sherratt, M. J., Derby, B., Richardson, S. M., & Hoyland, J. A. (2014). Growth differentiation factor 6 and transforming growth factor-beta differentially mediate mesenchymal stem cell differentiation, composition, and micromechanical properties of nucleus pulposus constructs. Arthritis Research & Therapy, 16(2), R67. https://doi.org/10.1186/ar4505
Costa, F. R., Pires, L., Martins, R. A., de Oliveira, M. G., Santos, G. S. S., Lana, J. F. S. D., et al. (2025). Orthobiologics revisited: A concise perspective on regenerative orthopedics. Current Issues in Molecular Biology, 47(4), 247. https://doi.org/10.3390/cimb47040247
Dai, W.-L., Zhou, A.-G., Zhang, H., & Zhang, J. (2017). Efficacy of platelet-rich plasma in the treatment of knee osteoarthritis: A meta-analysis of randomized controlled trials. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 33(3), 659–670.e1. https://doi.org/10.1016/j.arthro.2016.09.024
Dhurat, R., & Sukesh, M. S. (2014). Principles and methods of preparation of platelet-rich plasma: A review and author's perspective. Journal of Cutaneous and Aesthetic Surgery, 7(4), 189–197. https://doi.org/10.4103/0974-2077.150734
Ekstrand, J., Hägglund, M., & Waldén, M. (2011). Injury incidence and injury patterns in professional football: The UEFA injury study. British Journal of Sports Medicine, 45(7), 553–558. https://doi.org/10.1136/bjsm.2009.060582
Filardo, G., Kon, E., Di Martino, A., Di Matteo, B., Merli, M. L., Cenacchi, A., Fornasari, P. M., & Marcacci, M. (2012). Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: Study design and preliminary results of a randomized controlled trial. BMC Musculoskeletal Disorders, 13, 229. https://doi.org/10.1186/1471-2474-13-229
Filbay, S. R., Crossley, K. M., & Ackerman, I. N. (2016). Activity preferences, lifestyle modifications and re-injury fears influence longer-term quality of life in people with knee symptoms following anterior cruciate ligament reconstruction: A qualitative study. Journal of Physiotherapy, 62(2), 103–110. https://doi.org/10.1016/j.jphys.2016.02.011
Finch, C. (2006). A new framework for research leading to sports injury prevention. Journal of Science and Medicine in Sport, 9(1–2), 3–9. https://doi.org/10.1016/j.jsams.2006.02.009
Fong, E. L. S., Chan, C. K., & Goodman, S. B. (2011). Stem cell homing in musculoskeletal injury. Biomaterials, 32(2), 395–409. https://doi.org/10.1016/j.biomaterials.2010.08.101
Forsdyke, D., Smith, A., Jones, M., & Gledhill, A. (2016). Psychosocial factors associated with outcomes of sports injury rehabilitation in competitive athletes: A mixed studies systematic review. British Journal of Sports Medicine, 50(9), 537–544. https://doi.org/10.1136/bjsports-2015-094850
Gentile, P., Calabrese, C., De Angelis, B., Dionisi, L., Pizzicannella, J., Kothari, A., de Fazio, D., & Garcovich, S. (2020). Impact of the different preparation methods to obtain autologous non-activated platelet-rich plasma (A-PRP) and activated platelet-rich plasma (AA-PRP) in plastic surgery: Wound healing and hair regrowth evaluation. International Journal of Molecular Sciences, 21(2), 431. https://doi.org/10.3390/ijms21020431
Gentile, P., Cole, J. P., Cole, M. A., Garcovich, S., Bielli, A., Scioli, M. G., Orlandi, A., Insalaco, C., & Cervelli, V. (2017). Evaluation of not-activated and activated PRP in hair loss treatment: Role of growth factor and cytokine concentrations obtained by different collection systems. International Journal of Molecular Sciences, 18(2), 408. https://doi.org/10.3390/ijms18020408
Gupta, P. K., Chullikana, A., Rengasamy, M., Shetty, N., Pandey, V., Agarwal, V., Sharma, A., Verma, R. S., Rajagopal, K., & Majumdar, A. S. (2016). Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel®): Preclinical and clinical trial in osteoarthritis of the knee joint. Arthritis Research & Therapy, 18, 301. https://doi.org/10.1186/s13075-016-1195-7
Hashemi-Afzal, F., Haugh, M. G., Kelly, D. J., & O’Brien, F. J. (2024). Advancements in hydrogel design for articular cartilage regeneration: A comprehensive review. Journal of Orthopaedic Translation, 49, 182–195. https://doi.org/10.1016/j.jot.2024.08.001
Henriksson, H. B., Svanvik, T., Jonsson, M., Hagman, M., Horn, M., Lindahl, A., & Brisby, H. (2009). Transplantation of human mesenchymal stem cells into intervertebral discs in a xenogeneic porcine model. Spine, 34(2), 141–148. https://doi.org/10.1097/BRS.0b013e31818f8c20
Huang, Y., He, B., Wang, L., Yuan, B., Shu, H., Zhang, F., & Sun, L. (2020). Bone marrow mesenchymal stem cell-derived exosomes promote rotator cuff tendon-bone healing by promoting angiogenesis and regulating M1 macrophages in rats. Stem Cell Research & Therapy, 11(1), 496. https://doi.org/10.1186/s13287-020-02005-x
Jacho, D., & Yildirim-Ayan, E. (2024). Mechanome-guided strategies in regenerative rehabilitation. Current Opinion in Biomedical Engineering, 29, 100516. https://doi.org/10.1016/j.cobme.2023.100516
Kang, Y., Guan, Y., & Li, S. (2024). Innovative hydrogel solutions for articular cartilage regeneration: A comprehensive review. International Journal of Surgery, 110(12), 7984–8001. https://doi.org/10.1097/JS9.0000000000002076
Kjaer, M., Langberg, H., Miller, B. F., Boushel, R. C., Crameri, R., Koskinen, S., Heinemeier, K. M., Olesen, J. L., Døssing, S., Hansen, M., Pedersen, S. G., Rennie, M. J., & Magnusson, P. (2005). Metabolic activity and collagen turnover in human tendon in response to physical activity. Journal of Musculoskeletal & Neuronal Interactions, 5(1), 41–52.
Kon, E., Mandelbaum, B., Buda, R., Filardo, G., Delcogliano, M., Timoncini, A., Fornasari, P. M., Giannini, S., & Marcacci, M. (2011). Platelet-rich plasma intra-articular injection versus hyaluronic acid viscosupplementation as treatments for cartilage pathology: From early degeneration to osteoarthritis. Arthroscopy: The Journal of Arthroscopic & Related Surgery, 27(11), 1490–1501. https://doi.org/10.1016/j.arthro.2011.05.011
Liu, G., Wei, X., Zhai, Y., Zhang, J., Li, J., Zhao, Z., Guan, T., & Zhao, D. (2024). 3D printed osteochondral scaffolds: Design strategies, present applications and future perspectives. Frontiers in Bioengineering and Biotechnology, 12, 1339916. https://doi.org/10.3389/fbioe.2024.1339916
Magnusson, S. P., & Kjaer, M. (2019). The impact of loading, unloading, ageing and injury on the human tendon. The Journal of Physiology, 597(5), 1283–1298. https://doi.org/10.1113/JP275450
McIntyre, J. A., Jones, I. A., Han, B., & Vangsness, C. T., Jr. (2018). Intra-articular mesenchymal stem cell therapy for the human joint: A systematic review. The American Journal of Sports Medicine, 46(14), 3550–3563. https://doi.org/10.1177/0363546517735844
Milano, G., Sanna Passino, E., Deriu, L., Careddu, G., Manunta, L., Manunta, A., Saccomanno, M. F., & Fabbriciani, C. (2010). The effect of platelet rich plasma combined with microfractures on the treatment of chondral defects: An experimental study in a sheep model. Osteoarthritis and Cartilage, 18(7), 971–980. https://doi.org/10.1016/j.joca.2010.03.013
Molnar, V., Matišić, V., Kodvanj, I., Bjelica, R., Jeleč, Ž., Hudetz, D., et al. (2022). Mesenchymal stem cell mechanisms of action and clinical effects in osteoarthritis: A narrative review. Genes, 13(6), 949. https://doi.org/10.3390/genes13060949
Nyland, J., Pyle, B., Krupp, R., Kittle, G., Richards, J., & Brey, J. (2022). ACL microtrauma: Healing through nutrition, modified sports training, and increased recovery time. Journal of Experimental Orthopaedics, 9, 121. https://doi.org/10.1186/s40634-022-00561-0
Orozco, L., Soler, R., Morera, C., Alberca, M., Sánchez, A., & García-Sancho, J. (2011). Intervertebral disc repair by autologous mesenchymal bone marrow cells: A pilot study. Transplantation, 92(7), 822–828. https://doi.org/10.1097/TP.0b013e3182298a15
Peters, M. D. J., Godfrey, C. M., Khalil, H., McInerney, P., Parker, D., & Soares, C. B. (2015). Guidance for conducting systematic scoping reviews. International Journal of Evidence-Based Healthcare, 13(3), 141–146. https://doi.org/10.1097/XEB.0000000000000050
Podlog, L., & Eklund, R. C. (2007). The psychosocial aspects of a return to sport following serious injury: A review of the literature from a self-determination perspective. Psychology of Sport and Exercise, 8(4), 535–566. https://doi.org/10.1016/j.psychsport.2006.07.008
Riboh, J. C., Saltzman, B. M., Yanke, A. B., Fortier, L., & Cole, B. J. (2016). Effect of leukocyte concentration on the efficacy of platelet-rich plasma in the treatment of knee osteoarthritis. The American Journal of Sports Medicine, 44(3), 792–800. https://doi.org/10.1177/0363546515580787
Shi, S., & Gronthos, S. (2003). Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp. Journal of Bone and Mineral Research, 18(4), 696–704. https://doi.org/10.1359/jbmr.2003.18.4.696
Sun, Y., Feng, Y., Zhang, C.-Q., Chen, S.-B., & Cheng, X.-G. (2010). The regenerative effect of platelet-rich plasma on healing in large osteochondral defects. International Orthopaedics, 34(4), 589–597. https://doi.org/10.1007/s00264-009-0793-2
Tan, F., Zhao, Y., Han, X., Wang, H., Zhang, Y., Liu, H., Yi, F., Li, Z., Zhang, J., & Zhang, H. (2024). Clinical applications of stem cell-derived exosomes. Signal Transduction and Targeted Therapy, 9, 26. https://doi.org/10.1038/s41392-023-01704-0
Tricco, A. C., Lillie, E., Zarin, W., et al. (2018). PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Annals of Internal Medicine, 169(7), 467–473. https://doi.org/10.7326/M18-0850
van der Horst, N., Backx, F. J. G., Goedhart, E. A., & Huisstede, B. M. A. (2017). Return to play after hamstring injuries in football (soccer): A worldwide Delphi procedure regarding definition, medical criteria and decision-making. British Journal of Sports Medicine, 51(22), 1583–1591. https://doi.org/10.1136/bjsports-2016-097206
Wei, L.-C., Gao, S.-G., Xu, M., Jiang, W., Tian, J., & Lei, G.-H. (2012). A novel hypothesis: The application of platelet-rich plasma can promote the clinical healing of white-white meniscal tears. Medical Science Monitor, 18(8), HY47–HY50. https://doi.org/10.12659/MSM.883254
Xie, X., Wu, H., Zhao, S., Xie, G., Huangfu, X., & Zhao, J. (2013). The effect of platelet-rich plasma on patterns of gene expression in a dog model of anterior cruciate ligament reconstruction. Journal of Surgical Research, 180(1), 80–88. https://doi.org/10.1016/j.jss.2012.10.036
Xu, T., Binder, K. W., Albanna, M. Z., Dice, D., Zhao, W., Yoo, J. J., & Atala, A. (2013). Hybrid printing of mechanically and biologically improved constructs for cartilage tissue engineering applications. Biofabrication, 5(1), 015001. https://doi.org/10.1088/1758-5082/5/1/015001
Zhang, J., et al. (2025). Stem cell-derived exosomes: A comprehensive review of biological mechanisms, engineering strategies, and therapeutic applications. International Journal of Nanomedicine. https://doi.org/10.2147/IJN.S527137
Zhang, Y., et al. (2023). Mechanisms and therapeutic prospects of mesenchymal stem cells-derived exosomes for tendinopathy. Stem Cell Research & Therapy, 14, 307. https://doi.org/10.1186/s13287-023-03431-3
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Katarzyna Szlachetka, Aleksandra Gralec, Piotr Helbin
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
How to Cite
