Abstract
In the setting of biological augmentation for meniscus repair, it is extremely important to evaluate all aspects, including effectiveness, costs, potential risks, benefits, and limitations. It seems that everything matters in healing: the aspirate source of the bioactive agents, cell content, presence of stem cells and their type, growth factors, cytokines, biomechanical scaffold, and the quality of the tissue. There are several differences among mesenchymal, adipose, and peripheral blood stem cells, with the cell origin affecting the differentiation potential towards bone, cartilage and ligament. Moreover, different aspirate sources and fibrin clots have different content in cells, growth factors, and cytokines. In this equation, it is not as simple as the more the better. Different doses of growth factors may have different effects in the different cell types. And as this was not complicated enough, synergistic phenomena between cells and between growth factors can play a huge role. Add to that the role of the biomechanical environment, the proper timing of the healing phases and the inherent patient characteristics. There is very, very much to learn, and finally, we acknowledge that not all menisci repairs can always heal.
With recent advances in arthroscopic surgery, the task to “save the meniscus” is now possible not only for simple tears at the red–red vascular zone, but also in more complicated tears. The new challenge has become to attempt to successfully repair menisci tears even in the most difficult scenarios. Would it be possible to further enhance the biological and biomechanical environment of a repaired meniscus so it can successfully heal?
In their article, “Biochemical Characteristics and Clinical Result of Bone Marrow–Derived Fibrin Clot For Repair of Isolated Meniscal Injury in the Avascular Zone,” Hashimoto, Nishino, Orita, Yamasaki, Nishida, Kinoshita, and Nakamura demonstrated a greater concentration in growth factors in bone marrow aspirate (BMA) fibrin clot compared with peripheral blood clot as well as with BMA and peripheral blood aspirates.
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They also used BMA clots in meniscus repairs of horizontal, radial, and flap tear, with promising results.2
When attempting to generalize these findings, careful evaluation of the meniscus tear characteristics and the patient population is important. For example, 23 of 30 tears were discoid meniscus tears, and patient mean age was 23.2 ± 9.6 years (range 13-46 years). This study provides early promising data supporting the use of BMA clot for meniscus tears. However, limitations, such as the lack of control group and the relatively low postoperative Tegner activity scale, highlight the need for additional and high level of evidence studies comparing the new biologic augmentation techniques.To advance outcomes in meniscus repair, 2 main strategic areas require further development. The first strategy is to improve the biomechanical quality of the repair at time zero and during the healing phase. On that front, several new ideas have recently shown promise using better tools, configurations, and materials to provide a stronger fixation and improved outcome.
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Adopting all these strategies has resulted in expanding the indications for meniscus repair with healing rates that continuously improve, even in types of meniscus tears that would be considered nonrepairable in the past.8
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Second, we ought to further enhance the biologic environment of healing, applying evolving knowledge for scaffolds, cells, and growth factors. Ongoing research will lead to exciting stories of regeneration, vascularization, and stem cells with potential for application in meniscus tears.
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However, it is extremely important to understand the complexity of the biology of meniscus healing. And this complexity may explain the unpredictability of clinical success in meniscus healing.It seems that everything matters in healing: the aspirate source of the bioactive agents, cell content, presence of stem cells and their type, growth factors, cytokines, biomechanical scaffold, and the quality of the tissue. There are several differences among mesenchymal, adipose, and peripheral blood stem cells, with the cell origin affecting the differentiation potential toward bone, cartilage, and ligament.
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Moreover, different aspirate sources and fibrin clots have different content in cells, growth factors, and cytokines.14
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In this equation, it is not as simple as the more the better. Different doses of growth factors may have different effects in the different cell types.18
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And if this was not complicated enough, synergistic phenomena between cells and between growth factors can play a huge role.15
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Add to that the role of the biomechanical environment, the proper timing of the healing phases, and the inherent patient characteristics, this is a pretty hard problem to solve.In the setting of biological augmentation for meniscus repair, it is extremely important to evaluate all aspects, including effectiveness, costs, potential risks, benefits, and limitations. Additional research is needed to shed more light in this fascinating microworld. More importantly, we need to ensure that all these amazing tools are used with appropriate clinical indications and that we acknowledge that not all menisci repairs can always heal.
Supplementary Data
- ICMJE author disclosure forms
References
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- Growth factors and fibrochondrocytes in scaffolds.J Orthop Res. 2005; 23: 1184-1190
- Effect of dose and release rate of CTGF and TGFβ3 on avascular meniscus healing.J Orthop Res. 2019; 37: 1555-1562
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- Combined use of chondroitinase-ABC, TGF-β1, and collagen crosslinking agent lysyl oxidase to engineer functional neotissues for fibrocartilage repair.Biomaterials. 2014; 35: 6787-6796
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Footnotes
The author reports the following potential conflicts of interest or sources of funding: personal fees from the Arthroscopic Association of North America, during the conduct of the study. Full ICMJE author disclosure forms are available for this article online, as supplementary material.
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