Nasal Chondrocyte–Based Engineered Grafts for the Repair of Articular Cartilage “Kissing” Lesions: A Pilot Large-Animal Study

Background: Bipolar or “kissing” cartilage lesions formed on 2 opposite articular surfaces of the knee joint are commonly listed as exclusion criteria for advanced cartilage therapies. Purpose: To test, in a pilot large-animal study, whether autologous nasal chondrocyte (NC)–based tissue engineering, recently introduced for the treatment of focal cartilage injuries, could provide a solution for challenging kissing lesions. Study Design: Controlled laboratory study. Methods: Osteochondral kissing lesions were freshly introduced into the knee joints of 26 sheep and covered with NC-based grafts with a low or high hyaline-like extracellular matrix; a control group was treated with a cell-free scaffold collagen membrane (SCA). The cartilage repair site was assessed at 6 weeks and 6 months after implantation by histology, immunohistochemistry, and magnetic resonance imaging evaluation. Results: NC-based grafts, independently of their composition, induced partial hyaline cartilage repair with stable integrity in surrounding healthy tissue at 6 months after treatment. The SCA repaired cartilage to a similar degree to that of NC-based grafts. Conclusion: Kissing lesion repair, as evidenced in this sheep study, demonstrated the feasibility of the treatment of complex cartilage injuries with advanced biological methods. However, the potential advantages of an NC-based approach over a cell-free approach warrant further investigations in a more relevant preclinical model. Clinical Relevance: NC-based grafts currently undergoing phase II clinical trials have a high potential to replace existing cartilage therapies that show significant limitations in the quality and reproducibility of the repair method. We have brought this innovative concept to the next level by addressing a new clinical indication.

Prevention of Ischemic Myocardial Contracture Through Hemodynamically Controlled DCD

Purpose Ischemic myocardial contracture (IMC) or “stone heart” is a condition with rapid onset following circulatory death. It inhibits transplantability of hearts donated upon circulatory death (DCD). We investigate the effectiveness of hemodynamic normalization upon withdrawal of life-sustaining therapy (WLST) in a large-animal controlled DCD model, with the hypothesis that reduction in cardiac work delays the onset of IMC. Methods A large-animal study was conducted comprising of a control group ($$n=6$$ n = 6 ) receiving no therapy upon WLST, and a test group ($$n=6$$ n = 6 ) subjected to a protocol for fully automated computer-controlled hemodynamic drug administration. Onset of IMC within 1 h following circulatory death defined the primary end-point. Cardiac work estimates based on pressure-volume loop concepts were developed and used to provide insight into the effectiveness of the proposed computer-controlled therapy. Results No test group individual developed IMC within $${1} \text { h}$$ 1 h , whereas all control group individuals did (4/6 within $${30}{\text { min}}$$ 30 min ). Conclusion Automatic dosing of hemodynamic drugs in the controlled DCD context has the potential to prevent onset of IMC up to $${1}{\text { h}}$$ 1 h , enabling ethical and medically safe organ procurement. This has the potential to increase the use of DCD heart transplantation, which has been widely recognized as a means of meeting the growing demand for donor hearts.