Knee articular cartilage injuries cause pain, lead to poor joint function and disability. The spontaneous healing of cartilage lesions is poor and their treatment is still a challenge for orthopedic surgeons. If left untreated, these lesions may predispose to osteoarthritis and ultimately total joint replacement.
Cartilage repair procedures have the potential to relieve pain, improve the quality of life in younger patients and may delay or eliminate the need for joint replacement in the elderly. However, current treatments still have major drawbacks such as poor quality of repair tissue in comparison to native cartilage. The implantation of autologous articular chondrocytes (AC, cells harvested from a small biopsy of the patient’s own knee cartilage) at the damaged site to induce cartilage regeneration has represented a major breakthrough in the field. However, probably due to the variable quality of the cells used, even these treatments cannot yet offer predictable, reproducible and durable restoration of cartilage structure and function.
The BIO-CHIP project introduces two innovations with the potential to improve the clinical outcome of cartilage repair:
• use of a different source of cells: cells (Nasal Chondrocytes, NC) are harvested from the nasal septum of patients with limited risk of donor-site morbidity. Moreover, NC have been shown to have a higher and more reproducible capacity to regenerate cartilage tissue than AC. Additionally, NC can adapt to the joint environment acquiring the expression of molecules characteristic of AC and can withstand mechanical forces associated with weight bearing as well as inflammation associated with trauma and surgery;
• engineering of a mature cartilage tissue: the NC-based implant can be developed to various degrees of functional maturation depending on the culture time. In particular, NC,-based grafts can reproducibly reach biochemical and mechanical maturation approaching that of native cartilage, in contrast to typical tissues engineered using AC. A more mature tissue could offer higher functionality upon implantation and superior long-term performance, though this hypothesis has never been clinically tested.
The BIO-CHIP project targets two main objectives:
• conduct a multicenter (Croatia, Germany, Italy and Switzerland), prospective, phase II clinical study to treat 108 patients to determine the effect of maturation of NC-based cartilage grafts on the clinical outcome;
• explore in a large animal model the possibility to extend the clinical indications of the engineered grafts from acute, traumatic cartilage injuries to currently untreatable, degenerative cases (pre-osteoarthritic lesions).
In the multicenter clinical trial, 100 of 108 patients could be included, thus reaching the critical number of 97 patients, statistically required according to a power analysis to reach the objective of the study. Follow-up of patients is still ongoing, so no conclusion about the effect of maturation can be drawn yet. However, preliminary results indicate that most patients could benefit from the treatment. Animal experiments have shown, that grafts are also applicable in biomechanically challenging indications, such as kissing lesions. This is currently a contraindication for all cartilage repair products on the market.
