Orthobiologics 2024: Definition, Manufacturing, and Mechanism of Action of the Most Commonly Used Alternatives Currently Used in Orthopedics
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Published:
Aug 20, 2024
Keywords:
Orthobiologics, platelet-rich plasma, bone marrow concentrate, concéntrate, cell cultures, adipose-derived mesenchymal cells
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Abstract
Orthobiologics is emerging as a new subspecialty of orthopedics, with gradual acceptance. While platelet-rich plasma (PRP) and bone marrow concentrate (BMC) provided the initial catalyst for the widespread use of biological therapies in orthopedics due to their ease of preparation and application, there have been significant advances in the last decade, with numerous clinical evidence emerging on the outcomes of other promising biological therapies such as platelet lysate, adipose-derived stromal vascular fraction cells (SVF), and cell cultures. The following article aims to describe the most widely used biological therapies currently used in orthopedics, with special emphasis on their manufacturing process, composition, and mechanism of action.
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How to Cite
Rossi, L., & Levi, L. (2024). Orthobiologics 2024: Definition, Manufacturing, and Mechanism of Action of the Most Commonly Used Alternatives Currently Used in Orthopedics. Revista De La Asociación Argentina De Ortopedia Y Traumatología, 89(4), 431-439. https://doi.org/10.15417/issn.1852-7434.2024.89.4.1920
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References
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Biotechnol 2017;35(2):91-3. https://doi.org/10.1016/j.tibtech.2016.11.001
11. Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-rich plasma: New performance understandings and
therapeutic considerations in 2020. Int J Mol Sci 2020;21(20):7794. https://doi.org/10.3390/ijms21207794
12. Marx R. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 2004;62(4):489-96.
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essential for establishingepiphyseal vascularization and regulating chondrocyte development and survival. J Clin
Invest 2004;113(2):188-99. https://doi.org/10.1172/JCI19383
19. Bethany EL, Kisiday JD, Bahney CS, Ehrhart NP, Goodrich LR. The platelet-rich plasma and mesenchymal stem
cell milieu: A review of therapeutic effects on bone healing. J Orthop Res 2020;38(12):2539-50.
https://doi.org/10.1002/jor.24786
20. da Fonseca L, Silva Santos G, Cares Huber S, Mazzini Setti T, Setti T, Lana FJ. Human platelet lysate - A potent
(and overlooked) orthobiologic. J Clin Orthop Trauma 2021;21:101534. https://doi.org/10.1016/j.jcot.2021.101534
21. Magalon J, Chateau AL, Bertrand B, Louis ML, Silvestre A, Giraudo L, et al. DEPA classification: A proposal
for standardising PRP use and a retrospective application of available devices. BMJ Open Sport Exerc Med
2016;2(1):e000060. https://doi.org/10.1136/bmjsem-2015-000060
22. Kolaparthy LK, Sanivarapu S, Moogla S, Kutcham RS. Adipose tissue-adequate, accessible regenerative material. Int J Stem Cells 2015;8(2):121-7. https://doi.org/10.15283/ijsc.2015.8.2.121
23. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98(5):1076-84.
https://doi.org/10.1002/jcb.20886
24. Kim SJ, Kim EK, Kim SJ, Song DH. Effects of bone marrow aspirate concentrate and platelet-rich plasma on
patients with partial tear of the rotator cuff tendon. J Orthop Surg Res 2018;13(1):1-7. https://doi.org/10.1186/s13018-017-0693-x
25. Zhao T, Yan W, Xu K, Qi Y, Dai X, Shi Z. Combined treatment with platelet-rich plasma and brain-derived
neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord
hemi-section model. Cytotherapy 2013;15(7):792-804. https://doi.org/10.1016/j.jcyt.2013.04.004
26. Tsuji W. Adipose-derived stem cells: Implications in tissue regeneration. World J Stem Cells 2014;6(3):312-21.
https://doi.org/10.4252/wjsc.v6.i3.312
27. Hede K, Christensen BB, Jensen J, Foldager CB, Lind M. Combined bone marrow aspirate and platelet-rich plasma for cartilage repair: Two-year clinical results. Cartilage 2019;13(1_suppl):937S-947S.
https://doi.org/10.1177/1947603519876329
2. Van Schaik KD, Lee KS. Orthobiologics: Diagnosis and treatment of common tendinopathies. Semin Musculoskelet Radiol 2021;25(6):735-44. https://doi.org/10.1055/s-0041-1735475
3. Rauck RC, Eliasberg CD, Rodeo S, Rodeo SA. Orthobiologics for the management of early arthritis in the middleaged athlete. Sports Med Arthrosc Rev 2022;30(2):e9-e16. https://doi.org/10.1097/JSA.0000000000000337
4. Panero AJ, Everts PA, Nakagawa H, Sussman W, Qin X. Basic science of allograft orthobiologics. Phys Med
Rehabil Clin N Am 2023;34(1):49-61. https://doi.org/10.1016/j.pmr.2022.08.005
5. Marx R, Carlson E, Eichstaedt R, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: growth factor
enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85(6):638-46.
https://doi.org/10.1016/s1079-2104(98)90029-4
6. Marx R. Platelet-rich plasma (PRP): what is PRP and what is not PRP? Implant Dent 2001;10(4):225-8.
https://doi.org/10.1097/00008505-200110000-00002
7. Malhotra A, Pelletier M, Yu Y, Walsh W. Can platelet-rich plasma (PRP) improve bone healing? A comparison
between the theory and experimental outcomes. Arch Orthop Trauma Surg 2013;133(2):153-65.
https://doi.org/10.1007/s00402-012-1641-1
8. Xin W, Wen J, Yaqiong Z, Yongqiang H, Yanxu Z, Xueli S, et al. Platelet-rich plasma therapy in the treatment of
diseases associated with orthopedic injuries. Tissue Eng Part B Rev 2020;26(6):571-85.
https://doi.org/10.1089/ten.TEB.2019.0292
9. Zheng C, Zhu Q, Liu X, Huang X, He C, Jiang L, et al. Effect of platelet-rich plasma (PRP) concentration
on proliferation, neurotrophic function and migration of Schwann cells in vitro. J Tissue Eng Regen Med
2016;10(5):428-3. https://doi.org/10.1002/term.1756
10. Anitua E, Prado R, Orive G. Allogeneic platelet rich plasma: at the dawn of an off-the-shelf therapy? Trends
Biotechnol 2017;35(2):91-3. https://doi.org/10.1016/j.tibtech.2016.11.001
11. Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-rich plasma: New performance understandings and
therapeutic considerations in 2020. Int J Mol Sci 2020;21(20):7794. https://doi.org/10.3390/ijms21207794
12. Marx R. Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 2004;62(4):489-96.
https://doi.org/10.1016/j.joms.2003.12.003
13. Heldin C, Westermark B. PDGF-like growth factors in autocrine stimulation of growth. J Cell Physiol Suppl
1987;133(Suppl 5):31-4. https://doi.org/10.1002/jcp.1041330407
14. Andrew J, Hoyland J, Freemont A, Marsh D. Platelet-derived growth factor expression in normally healing human fractures. Bone 1995;16(4):455-60. https://doi.org/10.1016/8756-3282(95)90191-4
15. Barry F, Boynton R, Liu B, Murphy J. Chondrogenic differentiation of mesenchymal stem cells from bone marrow: differentiation-dependent gene expression of matrix components. Exp Cell Res 2001;268(2):189-200.
https://doi.org/10.1006/excr.2001.5278
16. Lieberman J, Daluiski A, Einhorn T. The role of growth factors in the repair of bone biology and clinical
applications. J Bone Joint Surg 2002;84(6):1032-44. https://doi.org/10.2106/00004623-200206000-00022
17. Gerber H, Vu T, Ryan A, Kowalski J, Werb Z, FerraraN. VEGF couples’ hypertrophic cartilage remodeling,
ossification and angiogenesis during endochondral bone formation. Nat Med 1999;5(6):623-8.
https://doi.org/10.1038/9467
18. Maes C, Stockmans I, Moermans K, Van Looveren R, Smets N, Carmeliet P, et al. Soluble VEGF isoforms are
essential for establishingepiphyseal vascularization and regulating chondrocyte development and survival. J Clin
Invest 2004;113(2):188-99. https://doi.org/10.1172/JCI19383
19. Bethany EL, Kisiday JD, Bahney CS, Ehrhart NP, Goodrich LR. The platelet-rich plasma and mesenchymal stem
cell milieu: A review of therapeutic effects on bone healing. J Orthop Res 2020;38(12):2539-50.
https://doi.org/10.1002/jor.24786
20. da Fonseca L, Silva Santos G, Cares Huber S, Mazzini Setti T, Setti T, Lana FJ. Human platelet lysate - A potent
(and overlooked) orthobiologic. J Clin Orthop Trauma 2021;21:101534. https://doi.org/10.1016/j.jcot.2021.101534
21. Magalon J, Chateau AL, Bertrand B, Louis ML, Silvestre A, Giraudo L, et al. DEPA classification: A proposal
for standardising PRP use and a retrospective application of available devices. BMJ Open Sport Exerc Med
2016;2(1):e000060. https://doi.org/10.1136/bmjsem-2015-000060
22. Kolaparthy LK, Sanivarapu S, Moogla S, Kutcham RS. Adipose tissue-adequate, accessible regenerative material. Int J Stem Cells 2015;8(2):121-7. https://doi.org/10.15283/ijsc.2015.8.2.121
23. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98(5):1076-84.
https://doi.org/10.1002/jcb.20886
24. Kim SJ, Kim EK, Kim SJ, Song DH. Effects of bone marrow aspirate concentrate and platelet-rich plasma on
patients with partial tear of the rotator cuff tendon. J Orthop Surg Res 2018;13(1):1-7. https://doi.org/10.1186/s13018-017-0693-x
25. Zhao T, Yan W, Xu K, Qi Y, Dai X, Shi Z. Combined treatment with platelet-rich plasma and brain-derived
neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord
hemi-section model. Cytotherapy 2013;15(7):792-804. https://doi.org/10.1016/j.jcyt.2013.04.004
26. Tsuji W. Adipose-derived stem cells: Implications in tissue regeneration. World J Stem Cells 2014;6(3):312-21.
https://doi.org/10.4252/wjsc.v6.i3.312
27. Hede K, Christensen BB, Jensen J, Foldager CB, Lind M. Combined bone marrow aspirate and platelet-rich plasma for cartilage repair: Two-year clinical results. Cartilage 2019;13(1_suppl):937S-947S.
https://doi.org/10.1177/1947603519876329