Biologics in Sports Medicine
By: Jorge Chahla, M.D., Ph.D. and Kyle Kunze, M.D.
The ways we treat patients have improved thanks to several developments in refining patient selection, enhancing surgical techniques and optimizing recovery, and only continues to evolve. The application of biologics has been observed in all of these domains, though evidence as to the appropriateness and efficacy of their use has remained far behind the frequency of their administration in practice. Indeed, the vast use of biologics has been out of optimism and excitement derived from a paucity of high-quality evidence, and the level of public misinformation is not insignificant.1 We cannot fall short of continuing to appropriately define the optimal compositions of biologics we choose to administer and the specific indications for their use in order to treat our patients appropriately and optimize patient outcomes.
With this in mind, many exciting developments are on the horizon for the use of various biologics in sports medicine, and the potential applications are more extensive than ever before. The past few years have observed a substantial amount of research at the basic, animal, translational and clinical levels into amniotic-derived treatments,2-4 adipose-derived stem cells,5 bone marrow aspirate concentrate6, 7 and platelet-rich plasma.8, 9 Moreover, we are observing biologics increasingly being used to treat focal chondral defects10 and early osteoarthritis,11, 12 while others have studied their role in bone healing13 and ligament/tendon repair and reconstruction.14, 15 It is undeniable that the future of biologics holds much promise and is an area worthwhile of continued investigations. An area that deserves further exploration is the synovial fluid composition of the diseased joint. This will allow Orthopaedic Surgeons to understand how to best treat different scenarios (catabolic, inflammatory, degradative).
A high level of excitement and optimism is necessary in any research effort; however, until we can be confident in the available evidence, we must practice prudence in clinical settings as it pertains to administering these agents. Considerable challenges currently exist in the widespread lack of consensus on the optimal preparation, source, delivery method and dosing of biologic therapies.16-18 A mismatch between the clinical application of biologics and the lengthy process of understanding developmental processes through rigorous testing will put emerging biologic technologies at risk. On the contrary, developmental processes that respect the delicate balance between consumer and industry pressures along with the challenge of translational medicine will likely be sustained. To this end, clinicians should adhere to Food and Drug Administration guidelines and documents on recommendations; critically evaluate the evidence behind biologics; and consider the risk imposed on patients. It’s important to remember that when it comes to the future of biologics, slow and steady wins the race.
References
1. Murray, I.R., Chahla, J., Frank, R.M., et al. "Rogue Stem Cell Clinics." The Bone & Joint Journal. 2020;102-B:148-154.
2. McIntyre, J.A., Jones, I.A., Danilkovich, A., Vangsness Jr., CT. "The Placenta: Applications in Orthopaedic Sports Medicine." American Journal of Sports Medicine. 2018;46:234-247.
3. Huddleston, H.P., Cohn, M.R., Haunschild, E.D., Wong, S.E., Farr, J., Yanke, A.B. "Amniotic Product Treatments: Clinical and Basic Science Evidence." Current Reviews in Musculoskeletal Medicine. 2020;13:148-154.
4. You, Q., Liu, Z., Zhang, J., et al. "Human Amniotic Mesenchymal Stem Cell Sheets Encapsulating Cartilage Particles Facilitate Repair of Rabbit Osteochondral Defects." American Journal of Sports Medicine. 2020;48:599-611.
5. Kunze, K.N., Burnett, R.A., Wright-Chisem, J., Frank, R.M., Chahla, J. "Adipose-Derived Mesenchymal Stem Cell Treatments and Available Formulations." Current Reviews in Musculoskeletal Medicine. 2020;13:264-280.
6. Jones, I.A., Togashi, R., Wilson, M.L., Heckmann, N., Vangsness Jr., C.T. "Intraarticular Treatment Options for Knee Osteoarthritis." Nature Reviews Rheumatology. 2019;15:77-90.
7. Shapiro, S.A., Kazmerchak, S.E., Heckman, M.G., Zubair, A.C., O'Connor, M.I. "A Prospective, Single-Blind, Placebo-Controlled Trial of Bone Marrow Aspirate Concentrate for Knee Osteoarthritis." American Journal of Sports Medicine. 2017;45:82-90.
8. Cole, B.J., Karas, V., Hussey, K., Pilz, K., Fortier, L.A. "Hyaluronic Acid Versus Platelet-Rich Plasma: A Prospective, Double-Blind Randomized Controlled Trial Comparing Clinical Outcomes and Effects on Intraarticular Biology for the Treatment of Knee Osteoarthritis." American Journal of Sports Medicine. 2017;45:339-346.
9. Zheng, C., Lu, H., Tang, Y., et al. "Autologous Freeze-Dried, Platelet-Rich Plasma Carrying Icariin Enhances Bone-Tendon Healing in a Rabbit Model." American Journal of Sports Medicine. 2019;47:1964-1974.
10. Kraeutler, M.J., Chahla, J., LaPrade, R.F., Pascual-Garrido, C. "Biologic Options for Articular Cartilage Wear (Platelet-Rich Plasma, Stem Cells, Bone Marrow Aspirate Concentrate)." Clinical Journal of Sports Medicine. 2017;36:457-468.
11. Sherman, B.J., Chahla, J., Glowney, J., Frank, R.M. "The Role of Orthobiologics in the Management of Osteoarthritis and Focal Cartilage Defects." Orthopedics. 2019;42:66-73.
12. Chahla, J., Mandelbaum, B.R. "Biological Treatment for Osteoarthritis of the Knee: Moving from Bench to Bedside-Current Practical Concepts." Arthroscopy: The Journal of Arthroscopic and Related Surgery. 2018;34:1719-1729.
13. Miller, T.L., Kaeding, C.C., Rodeo, S.A. "Emerging Options for Biologic Enhancement of Stress Fracture Healing in Athletes." Journal of the American Academy of Orthopaedic Surgery. 2020;28:1-9.
14. Chahla, J., Kennedy, M.I., Aman, Z.S., LaPrade, R.F. "Orthobiologics for Ligament Repair and Reconstruction." Clinical Journal of Sports Medicine. 2019;38:97-107.
15. Dallo, I., Chahla, J., Mitchell, J.J., Pascual-Garrido, C., Feagin, J.A., LaPrade, R.F. "Biologic Approaches for the Treatment of Partial Tears of the Anterior Cruciate Ligament: A Current Concepts Review." Orthopaedic Journal of Sports Medicine. 2017;5:2325967116681724.
16. Murray, I.R., Chahla, J., Safran, M.R., et al. "International Expert Consensus on a Cell Therapy Communication Tool: DOSES." Journal of Bone and Joint Surgery -- American Volume. 2019;101:904-911.
17. Chahla, J., Cinque, M.E., Piuzzi, N.S., et al. "A Call for Standardization in Platelet-Rich Plasma Preparation Protocols and Composition Reporting: A Systematic Review of the Clinical Orthopaedic Literature." Journal of Bone and Joint Surgery -- American Volume. 2017;99:1769-1779.
18. Rodeo, S.A. "Cell Therapy in Orthopaedics: Where Are We in 2019?" The Bone & Joint Journal. 2019;101-B:361-364.