Biologic Knee Arthroplasty in 360 Degrees for Early Osteoarthritis Treatment
Main Article Content
Abstract
This article gives a comprehensive review of a two-step single surgical alternative that searches to preserve the patient's cartilage and joint. It addresses the knee from a 360-degree perspective; First, from the articular side, full-thickness cartilage lesions are treated with hyaluronic acid (HA) scaffold combined with bone marrow aspirate concentrate (BMC), which restores the articular cartilage with a hyaline-like tissue. Then, deep inside the subchondral bone, a minimally invasive procedure called Osteo-Core-Plasty (OCP) is conducted when it is affected. This procedure serves to restore the subchondral bone with structural bone autograft and BMAC derived signaling cells. The HA-BMC cartilage preserving technique with more than ten years of follow-up provides persistent and prothesis sparing surgical results, while OCP offers the further benefits of the new technology for deep joint bone-core treatment and regeneration with significant improvement in clinical score outcomes and magnetic resonance imaging. Given the evidence, these articular preservation techniques can be considered the new paradigm knee arthroplasty surgery as they can achieve a valuable and holistic approach to early osteoarthritis treatment.
Keywords:
stem cells, scaffold, osteoarthritis, hyaluronic acid, cartilage regeneration, subchondral bone, bio-orthopaedics
Article Details
How to Cite
GOBBI, Alberto; MORALES, Macarena; VALSECCHI, Giacomo.
Biologic Knee Arthroplasty in 360 Degrees for Early Osteoarthritis Treatment.
Medical Research Archives, [S.l.], v. 10, n. 3, mar. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2717>. Date accessed: 24 dec. 2024.
doi: https://doi.org/10.18103/mra.v10i3.2717.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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3. Silverwood V, Blagojevic-Bucknall M, Jinks C, Jordan JL, Protheroe J, Jordan KP. Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthr Cartil. 2015;23(4):507-515. doi:10.1016/J.JOCA.2014.11.019
4. Vigdorchik JM, Nepple JJ, Eftekhary N, Leunig M, Clohisy JC. What Is the Association of Elite Sporting Activities With the Development of Hip Osteoarthritis?: https://doi.org/101177/0363546516656359. 2016;45(4):961-964. doi:10.1177/0363546516656359
5. Gobbi A, Lane J, Giuseppe L, Dallo I. Joint Function Preservation; A Focus on the Osteochondral Unit. SPRINGER NATURE; 2021.
6. Bierma-Zeinstra SMA, Waarsing JH. The role of atherosclerosis in osteoarthritis. Best Pract Res Clin Rheumatol. 2017;31(5):613-633. doi:10.1016/J.BERH.2018.08.006
7. Hall AJ, Stubbs B, Mamas MA, Myint PK, Smith TO. Association between osteoarthritis and cardiovascular disease: Systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23(9):938-946. doi:10.1177/2047487315610663
8. Widuchowski W, Widuchowski J, Trzaska T. Articular cartilage defects: Study of 25,124 knee arthroscopies. Knee. 2007;14(3):177-182. doi:10.1016/j.knee.2007.02.001
9. Flanigan DC, Harris JD, Trinh TQ, Siston RA, Brophy RH. Prevalence of chondral defects in Athletes' Knees: A systematic review. Med Sci Sports Exerc. 2010;42(10):1795-1801. doi:10.1249/MSS.0b013e3181d9eea0
10. Hunter W. Of the structure and disease of articulating cartilages. 1743. Clin Orthop Relat Res. 1995;(317):3-6. Accessed January 19, 2022. https://pubmed.ncbi.nlm.nih.gov/7671493/
11. Gobbi A, Lane JG, Dallo I. Editorial Commentary: Cartilage Restoration—What Is Currently Available? Arthrosc - J Arthrosc Relat Surg. 2020;36(6):1625-1628. doi:10.1016/j.arthro.2020.04.001
12. Kon E, Filardo G, Gobbi A, et al. Long-term Results after Hyaluronan-based M.A.C.T. for the Treatment of Cartilage Lesions of the Patellofemoral Joint. Am J Sports Med. 2016;44(3):602-608. doi:10.1177/0363546515620194
13. Tuli R, Li WJ, Tuan RS. Current state of cartilage tissue engineering. Arthritis Res Ther. 2003;5(5):235. doi:10.1186/AR991
14. Dovedytis M, Liu ZJ, Bartlett S. Hyaluronic acid and its biomedical applications: A review. Eng Regen. 2020;1:102-113. doi:10.1016/J.ENGREG.2020.10.001
15. Grigolo B, Lisignoli G, Piacentini A, et al. Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAFF®11): Molecular, immunohistochemical and ultrastructural analysis. Biomaterials. 2002;23(4):1187-1195. doi:10.1016/S0142-9612(01)00236-8
16. Gobbi A, Whyte GP. Long-term clinical outcomes of one-stage cartilage repair in the knee with hyaluronic acid–based scaffold embedded with mesenchymal stem cells sourced from bone marrow aspirate concentrate. Am J Sport Med. 2019;47:1621-1628.
17. Caplan AI. Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. Tissue Eng. 2005;11(7-8):1198-1211. doi:10.1089/TEN.2005.11.1198
18. Hellingman CA, Davidson E.N.B., Koevoet W, et al. Smad signaling determines chondrogenic differentiation of bone-marrow-derived mesenchymal stem cells: Inhibition of Smad1/5/8P prevents terminal differentiation and calcification. Tissue Eng - Part A. 2011;17(7-8):1157-1167. doi:10.1089/ten.tea.2010.0043
19. Pasquinelli G, Orrico C, Foroni L, et al. Mesenchymal stem cell interaction with a non-woven hyaluronan-based scaffold suitable for tissue repair. J Anat. 2008;213(5):520. doi:10.1111/J.1469-7580.2008.00974.X
20. Lisignoli G, Cristino S, Piacentini A, et al. Chondrogenic differentiation of murine and human mesenchymal stromal cells in a hyaluronic acid scaffold: Differences in gene expression and cell morphology. J Biomed Mater Res - Part A. 2006;77(3):497-506. doi:10.1002/jbm.a.30632
21. Gobbi A, Karnatzikos G, Petrera M. Biologic Arthroplasty for Full-thickness Cartilage Lesions of the Knee: Results at Three Years Follow-up (SS-56). Arthrosc J Arthrosc Relat Surg. 2013;29(6):e27. doi:10.1016/J.ARTHRO.2013.03.063
22. Gobbi A, Karnatzikos G, Scotti C, Mahajan V, Mazzucco L, Grigolo B. One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2-year follow-up. Cartilage. 2011;2(3):286-299. doi:10.1177/1947603510392023
23. Gobbi A, Whyte G.P.G.P. Long-term Clinical Outcomes of One-Stage Cartilage Repair in the Knee With Hyaluronic Acid–Based Scaffold Embedded With Mesenchymal Stem Cells Sourced From Bone Marrow Aspirate Concentrate. Am J Sports Med. 2019;47(7):1621-1628. doi:10.1177/0363546519845362
24. Whyte GP, Gobbi A, Sadlik B. Dry Arthroscopic Single-Stage Cartilage Repair of the Knee Using a Hyaluronic Acid-Based Scaffold With Activated Bone Marrow-Derived Mesenchymal Stem Cells. Arthrosc Tech. 2016;5(4):e913-e918. doi:10.1016/J.EATS.2016.04.020
25. Nejadnik H, Hui JH, Choong EPF, Tai BC, Eng Hin Lee. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010;38(6):1110-1116. doi:10.1177/0363546509359067
26. Gobbi A, Chaurasia S, Karnatzikos G, Nakamura N. Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial. Cartilage. 2015;6(2):82-97. doi:10.1177/1947603514563597
27. Gobbi A, Scotti C, Karnatzikos G, Mudhigere A, Castro M, Peretti GMGM. One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years. Knee Surgery, Sport Traumatol Arthrosc. 2017;25(8):2494-2501. doi:10.1007/s00167-016-3984-6
28. Sadlik B, Gobbi A, Puszkarz M, Klon W, Whyte GP. Biologic Inlay Osteochondral Reconstruction: Arthroscopic One-Step Osteochondral Lesion Repair in the Knee Using Morselized Bone Grafting and Hyaluronic Acid-Based Scaffold Embedded With Bone Marrow Aspirate Concentrate. Arthrosc Tech. 2017;6(2):e383-e389. doi:10.1016/J.EATS.2016.10.023
29. Gobbi A, Karnatzikos G, Lad D, Chaurasia S. Long-term Results after Microfracture Treatment of Full-thickness Knee Chondral Lesions in Athletes. Arthroscopy. 2014;30(6):e33. doi:10.1016/J.ARTHRO.2014.04.072
30. Gobbi A, Whyte G.P.G.P. One-Stage Cartilage Repair Using a Hyaluronic Acid-Based Scaffold with Activated Bone Marrow-Derived Mesenchymal Stem Cells Compared with Microfracture. Am J Sports Med. 2016;44(11):2846-2854. doi:10.1177/0363546516656179
31. Clark JM, Huber JD. The structure of the human subchondral plate. J Bone Joint Surg Br. 1990;72(5):866-873. doi:10.1302/0301-620X.72B5.2211774
32. Radin EL, Paul IL. Response of joints to impact loading. I. In vitro wear. Arthritis Rheum. 1971;14(3):356-362. doi:10.1002/ART.1780140306
33. McCarty D, a WK-A and allied conditions:, 1993 undefined. Arthritis and allied conditions: a textbook of rheumatology. pesquisa.bvsalud.org. Accessed January 12, 2022. https://pesquisa.bvsalud.org/portal/resource/pt/biblio-971453
34. Imhof H, Breitenseher M, Kainberger F, Rand T, Trattnig S. Importance of subchondral bone to articular cartilage in health and disease. Top Magn Reson Imaging. 1999;10(3):180-192. doi:10.1097/00002142-199906000-00002
35. L.B. L, A V, P.G. B, Lane LB, Villacin A, Bullough PG. The vascularity and remodelling of subchondrial bone and calcified cartilage in adult human femoral and humeral heads. An age- and stress-related phenomenon. J Bone Joint Surg Br. 1977;59(3):272-278. doi:10.1302/0301-620X.59B3.893504
36. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013;21(1):16-21. doi:10.1016/J.JOCA.2012.11.012
37. McIlwraith C, Frisbie D, Kawcak C, Weeren R Van. Joint disease in the horse. Published online 2015. Accessed January 12, 2022. https://books.google.com/books?hl=it&lr=&id=8LNgCgAAQBAJ&oi=fnd&pg=PP1&ots=WP_ob5QbRv&sig=aZMABdgIhJLog-Ml6cZTyt_zEdM
38. Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res. 1986;213(213):34-40. doi:10.1097/00003086-198612000-00005
39. Hernigou P, Bouthors C, Bastard C, Flouzat Lachaniette CH, Rouard H, Dubory A. Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study. Int Orthop. 2021;45(2):391-399. doi:10.1007/S00264-020-04687-7
40. Kon E, Boffa A, Andriolo L, et al. Subchondral and intra-articular injections of bone marrow concentrate are a safe and effective treatment for knee osteoarthritis: a prospective, multi-center pilot study. Knee Surg Sports Traumatol Arthrosc. 2021;29(12):4232-4240. doi:10.1007/S00167-021-06530-X
41. Szwedowski D, Dallo I, Irlandini E, Gobbi A. Osteo-core Plasty: A Minimally Invasive Approach for Subchondral Bone Marrow Lesions of the Knee. Arthrosc Tech. 2020;9(11). doi:10.1016/J.EATS.2020.07.023
42. Everts PA. Journal of Stem Cell Biology and Transplantation A comparative quantification in cellularity of bone marrow aspirated with two new har-vesting devices, and the nonequivalent difference between a centrifugated bone marrow concentrate and a bone marrow aspirate as biological injectates, using a bi-lateral patient model. J Stem Cell Biol Transpl 2020 Stem Cell Res. Published online 2020.
43. Hernigou P, Homma Y, Flouzat Lachaniette CH, et al. Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop. 2013;37(11):2279. doi:10.1007/S00264-013-2017-Z
44. Viganò M, Ragni E, Di Matteo B, et al. A single step, centrifuge-free method to harvest bone marrow highly concentrated in mesenchymal stem cells: results of a pilot trial. Int Orthop. Published online 2021. doi:10.1007/s00264-021-05243-7
45. Scarpone M, Kuebler D, Chambers A, et al. Isolation of clinically relevant concentrations of bone marrow mesenchymal stem cells without centrifugation 11 Medical and Health Sciences 1103 Clinical Sciences. J Transl Med. 2019;17(1):1-10. doi:10.1186/S12967-018-1750-X/FIGURES/2
46. Osteo-Core-PlastyTM with Marrow CellutionTM | Aspire Medical Innovation.
2. Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (G.B.D. 2019) results. 2020. http://ghdx.healthdata.org/gbd-results-tool (accessed Ago 8, 2020). Accessed August 10, 2021. http://ghdx.healthdata.org/gbd-results-tool
3. Silverwood V, Blagojevic-Bucknall M, Jinks C, Jordan JL, Protheroe J, Jordan KP. Current evidence on risk factors for knee osteoarthritis in older adults: a systematic review and meta-analysis. Osteoarthr Cartil. 2015;23(4):507-515. doi:10.1016/J.JOCA.2014.11.019
4. Vigdorchik JM, Nepple JJ, Eftekhary N, Leunig M, Clohisy JC. What Is the Association of Elite Sporting Activities With the Development of Hip Osteoarthritis?: https://doi.org/101177/0363546516656359. 2016;45(4):961-964. doi:10.1177/0363546516656359
5. Gobbi A, Lane J, Giuseppe L, Dallo I. Joint Function Preservation; A Focus on the Osteochondral Unit. SPRINGER NATURE; 2021.
6. Bierma-Zeinstra SMA, Waarsing JH. The role of atherosclerosis in osteoarthritis. Best Pract Res Clin Rheumatol. 2017;31(5):613-633. doi:10.1016/J.BERH.2018.08.006
7. Hall AJ, Stubbs B, Mamas MA, Myint PK, Smith TO. Association between osteoarthritis and cardiovascular disease: Systematic review and meta-analysis. Eur J Prev Cardiol. 2016;23(9):938-946. doi:10.1177/2047487315610663
8. Widuchowski W, Widuchowski J, Trzaska T. Articular cartilage defects: Study of 25,124 knee arthroscopies. Knee. 2007;14(3):177-182. doi:10.1016/j.knee.2007.02.001
9. Flanigan DC, Harris JD, Trinh TQ, Siston RA, Brophy RH. Prevalence of chondral defects in Athletes' Knees: A systematic review. Med Sci Sports Exerc. 2010;42(10):1795-1801. doi:10.1249/MSS.0b013e3181d9eea0
10. Hunter W. Of the structure and disease of articulating cartilages. 1743. Clin Orthop Relat Res. 1995;(317):3-6. Accessed January 19, 2022. https://pubmed.ncbi.nlm.nih.gov/7671493/
11. Gobbi A, Lane JG, Dallo I. Editorial Commentary: Cartilage Restoration—What Is Currently Available? Arthrosc - J Arthrosc Relat Surg. 2020;36(6):1625-1628. doi:10.1016/j.arthro.2020.04.001
12. Kon E, Filardo G, Gobbi A, et al. Long-term Results after Hyaluronan-based M.A.C.T. for the Treatment of Cartilage Lesions of the Patellofemoral Joint. Am J Sports Med. 2016;44(3):602-608. doi:10.1177/0363546515620194
13. Tuli R, Li WJ, Tuan RS. Current state of cartilage tissue engineering. Arthritis Res Ther. 2003;5(5):235. doi:10.1186/AR991
14. Dovedytis M, Liu ZJ, Bartlett S. Hyaluronic acid and its biomedical applications: A review. Eng Regen. 2020;1:102-113. doi:10.1016/J.ENGREG.2020.10.001
15. Grigolo B, Lisignoli G, Piacentini A, et al. Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAFF®11): Molecular, immunohistochemical and ultrastructural analysis. Biomaterials. 2002;23(4):1187-1195. doi:10.1016/S0142-9612(01)00236-8
16. Gobbi A, Whyte GP. Long-term clinical outcomes of one-stage cartilage repair in the knee with hyaluronic acid–based scaffold embedded with mesenchymal stem cells sourced from bone marrow aspirate concentrate. Am J Sport Med. 2019;47:1621-1628.
17. Caplan AI. Review: mesenchymal stem cells: cell-based reconstructive therapy in orthopedics. Tissue Eng. 2005;11(7-8):1198-1211. doi:10.1089/TEN.2005.11.1198
18. Hellingman CA, Davidson E.N.B., Koevoet W, et al. Smad signaling determines chondrogenic differentiation of bone-marrow-derived mesenchymal stem cells: Inhibition of Smad1/5/8P prevents terminal differentiation and calcification. Tissue Eng - Part A. 2011;17(7-8):1157-1167. doi:10.1089/ten.tea.2010.0043
19. Pasquinelli G, Orrico C, Foroni L, et al. Mesenchymal stem cell interaction with a non-woven hyaluronan-based scaffold suitable for tissue repair. J Anat. 2008;213(5):520. doi:10.1111/J.1469-7580.2008.00974.X
20. Lisignoli G, Cristino S, Piacentini A, et al. Chondrogenic differentiation of murine and human mesenchymal stromal cells in a hyaluronic acid scaffold: Differences in gene expression and cell morphology. J Biomed Mater Res - Part A. 2006;77(3):497-506. doi:10.1002/jbm.a.30632
21. Gobbi A, Karnatzikos G, Petrera M. Biologic Arthroplasty for Full-thickness Cartilage Lesions of the Knee: Results at Three Years Follow-up (SS-56). Arthrosc J Arthrosc Relat Surg. 2013;29(6):e27. doi:10.1016/J.ARTHRO.2013.03.063
22. Gobbi A, Karnatzikos G, Scotti C, Mahajan V, Mazzucco L, Grigolo B. One-step cartilage repair with bone marrow aspirate concentrated cells and collagen matrix in full-thickness knee cartilage lesions: results at 2-year follow-up. Cartilage. 2011;2(3):286-299. doi:10.1177/1947603510392023
23. Gobbi A, Whyte G.P.G.P. Long-term Clinical Outcomes of One-Stage Cartilage Repair in the Knee With Hyaluronic Acid–Based Scaffold Embedded With Mesenchymal Stem Cells Sourced From Bone Marrow Aspirate Concentrate. Am J Sports Med. 2019;47(7):1621-1628. doi:10.1177/0363546519845362
24. Whyte GP, Gobbi A, Sadlik B. Dry Arthroscopic Single-Stage Cartilage Repair of the Knee Using a Hyaluronic Acid-Based Scaffold With Activated Bone Marrow-Derived Mesenchymal Stem Cells. Arthrosc Tech. 2016;5(4):e913-e918. doi:10.1016/J.EATS.2016.04.020
25. Nejadnik H, Hui JH, Choong EPF, Tai BC, Eng Hin Lee. Autologous bone marrow-derived mesenchymal stem cells versus autologous chondrocyte implantation: an observational cohort study. Am J Sports Med. 2010;38(6):1110-1116. doi:10.1177/0363546509359067
26. Gobbi A, Chaurasia S, Karnatzikos G, Nakamura N. Matrix-Induced Autologous Chondrocyte Implantation versus Multipotent Stem Cells for the Treatment of Large Patellofemoral Chondral Lesions: A Nonrandomized Prospective Trial. Cartilage. 2015;6(2):82-97. doi:10.1177/1947603514563597
27. Gobbi A, Scotti C, Karnatzikos G, Mudhigere A, Castro M, Peretti GMGM. One-step surgery with multipotent stem cells and Hyaluronan-based scaffold for the treatment of full-thickness chondral defects of the knee in patients older than 45 years. Knee Surgery, Sport Traumatol Arthrosc. 2017;25(8):2494-2501. doi:10.1007/s00167-016-3984-6
28. Sadlik B, Gobbi A, Puszkarz M, Klon W, Whyte GP. Biologic Inlay Osteochondral Reconstruction: Arthroscopic One-Step Osteochondral Lesion Repair in the Knee Using Morselized Bone Grafting and Hyaluronic Acid-Based Scaffold Embedded With Bone Marrow Aspirate Concentrate. Arthrosc Tech. 2017;6(2):e383-e389. doi:10.1016/J.EATS.2016.10.023
29. Gobbi A, Karnatzikos G, Lad D, Chaurasia S. Long-term Results after Microfracture Treatment of Full-thickness Knee Chondral Lesions in Athletes. Arthroscopy. 2014;30(6):e33. doi:10.1016/J.ARTHRO.2014.04.072
30. Gobbi A, Whyte G.P.G.P. One-Stage Cartilage Repair Using a Hyaluronic Acid-Based Scaffold with Activated Bone Marrow-Derived Mesenchymal Stem Cells Compared with Microfracture. Am J Sports Med. 2016;44(11):2846-2854. doi:10.1177/0363546516656179
31. Clark JM, Huber JD. The structure of the human subchondral plate. J Bone Joint Surg Br. 1990;72(5):866-873. doi:10.1302/0301-620X.72B5.2211774
32. Radin EL, Paul IL. Response of joints to impact loading. I. In vitro wear. Arthritis Rheum. 1971;14(3):356-362. doi:10.1002/ART.1780140306
33. McCarty D, a WK-A and allied conditions:, 1993 undefined. Arthritis and allied conditions: a textbook of rheumatology. pesquisa.bvsalud.org. Accessed January 12, 2022. https://pesquisa.bvsalud.org/portal/resource/pt/biblio-971453
34. Imhof H, Breitenseher M, Kainberger F, Rand T, Trattnig S. Importance of subchondral bone to articular cartilage in health and disease. Top Magn Reson Imaging. 1999;10(3):180-192. doi:10.1097/00002142-199906000-00002
35. L.B. L, A V, P.G. B, Lane LB, Villacin A, Bullough PG. The vascularity and remodelling of subchondrial bone and calcified cartilage in adult human femoral and humeral heads. An age- and stress-related phenomenon. J Bone Joint Surg Br. 1977;59(3):272-278. doi:10.1302/0301-620X.59B3.893504
36. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthr Cartil. 2013;21(1):16-21. doi:10.1016/J.JOCA.2012.11.012
37. McIlwraith C, Frisbie D, Kawcak C, Weeren R Van. Joint disease in the horse. Published online 2015. Accessed January 12, 2022. https://books.google.com/books?hl=it&lr=&id=8LNgCgAAQBAJ&oi=fnd&pg=PP1&ots=WP_ob5QbRv&sig=aZMABdgIhJLog-Ml6cZTyt_zEdM
38. Radin EL, Rose RM. Role of subchondral bone in the initiation and progression of cartilage damage. Clin Orthop Relat Res. 1986;213(213):34-40. doi:10.1097/00003086-198612000-00005
39. Hernigou P, Bouthors C, Bastard C, Flouzat Lachaniette CH, Rouard H, Dubory A. Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study. Int Orthop. 2021;45(2):391-399. doi:10.1007/S00264-020-04687-7
40. Kon E, Boffa A, Andriolo L, et al. Subchondral and intra-articular injections of bone marrow concentrate are a safe and effective treatment for knee osteoarthritis: a prospective, multi-center pilot study. Knee Surg Sports Traumatol Arthrosc. 2021;29(12):4232-4240. doi:10.1007/S00167-021-06530-X
41. Szwedowski D, Dallo I, Irlandini E, Gobbi A. Osteo-core Plasty: A Minimally Invasive Approach for Subchondral Bone Marrow Lesions of the Knee. Arthrosc Tech. 2020;9(11). doi:10.1016/J.EATS.2020.07.023
42. Everts PA. Journal of Stem Cell Biology and Transplantation A comparative quantification in cellularity of bone marrow aspirated with two new har-vesting devices, and the nonequivalent difference between a centrifugated bone marrow concentrate and a bone marrow aspirate as biological injectates, using a bi-lateral patient model. J Stem Cell Biol Transpl 2020 Stem Cell Res. Published online 2020.
43. Hernigou P, Homma Y, Flouzat Lachaniette CH, et al. Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop. 2013;37(11):2279. doi:10.1007/S00264-013-2017-Z
44. Viganò M, Ragni E, Di Matteo B, et al. A single step, centrifuge-free method to harvest bone marrow highly concentrated in mesenchymal stem cells: results of a pilot trial. Int Orthop. Published online 2021. doi:10.1007/s00264-021-05243-7
45. Scarpone M, Kuebler D, Chambers A, et al. Isolation of clinically relevant concentrations of bone marrow mesenchymal stem cells without centrifugation 11 Medical and Health Sciences 1103 Clinical Sciences. J Transl Med. 2019;17(1):1-10. doi:10.1186/S12967-018-1750-X/FIGURES/2
46. Osteo-Core-PlastyTM with Marrow CellutionTM | Aspire Medical Innovation.