The intrinsic regenerative capacity of avascular cartilage is limited. Cartilage injuries result in chronic, non-healing lesions requiring surgical management. Frequently, these surgical techniques make use of allogeneic cells and tissues. This review discusses the immune status of these materials. Cartilage allografts, often used in orthopedic and plastic surgeries, have rarely provoked a significant immune response. In whole cartilage transplants, the dense matrix produced by chondrocytes inhibits lymphocyte migration, preventing immune detection rendering them "antigen sequestered." It is unclear whether isolated chondrocytes are immune-privileged; chondrocytes express immune inhibitory B7 molecules, indicating that they have some ability to modulate immune reactions. Allogeneic cartilage grafts often involve a bony portion often retaining immunogenic cells and proteins-to facilitate good surgical attachment and concern that this may enhance inflammation and immune rejection. However, studies of failed cartilage grafts have not found immune responses to be a contributing factor. Meniscus allografts, which also retain a bony portion, raise similar concerns as cartilage allografts. Despite this, the plugs improved patient outcomes, indicating that the immunological effects were not clinically significant. Finally, allogeneic mesenchymal stromal cells (MSCs) also are being investigated as a treatment for cartilage damage. MSCs have been demonstrated to have unique immunomodulatory properties including their ability to reduce immune cell infiltration and to modulate inflammation. In summary, the immunogenic properties of cartilage vary with the type of allograft used: Cartilage allografts demonstrate active immune-suppressive mechanisms as evidenced by lack of allograft rejection, while MSC allografts appear to be safe for transplantation.

This review summarizes recent developments in biologic treatments-including growth factors, platelet-rich plasma (PRP), stem cells, and cell-seeded scaffolds-for tendon repair. Growth and differentiation faction-5 (GDF-5), insulin-related growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF) all improved extracellular matrix (ECM) production and tensile strength of treated tendons; however, no clinical trials were done on GDF-5. Platelet-derived growth factor-BB (PDGF-BB) improved proliferation and ECM production, but did not consistently improve mechanical properties. The literature was mixed on the efficacy of PRP for the treatment of chronic and acute tendinopathies. However, PRP did cause any complications, and its benefits may be enhanced once an ideal, standardized composition is developed. Therefore, PRP may be a valid treatment, especially once nonsurgical management options have failed. Mesenchymal stem cells (MSCs) significantly and substantially improved the quality of tendon repairs and demonstrated the ability to regenerate an enthesis. Adipose-derived stem cells (ADSCs) have similar effects and are easier to harvest. The periosteum may also regenerate the tendon-bone attachment. Tenocytes, meanwhile, may be ideal for midsubstance tendon repairs. Cell-seeded scaffolds-especially ECMderived scaffolds-were demonstrated to improve ECM production, enhancing the healing abilities of tenocytes or stem cells while providing early mechanical support to healing tendons.Each of these treatments demonstrated enhanced healing compared to common surgical techniques; moreover, patient outcomes may be enhanced by combining these treatments. Lay SummaryTendon injuries are very prevalent and can be debilitating. Tendon heals poorly, and the scar tissue that forms is weak and susceptible to reinjury. A major focus of orthopedic research is regenerative medicine, encouraging the formation of healthy tendon rather than mechanically inferior scar tissue. This review summarizes the recent scientific literature on biologic treatments for tendon repair, such as growth factors, platelet-rich plasma, and stem cells. The purpose of which is to show which treatments are promising candidates for clinical use and research, helping to guide physicians and to lay out a path for future research.

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