טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentBar-Zvi Shira
SubjectTreating Joint Cartilage Damage by Xenotransplantation of
Tissue Engineered Hyaline Cartilage
DepartmentDepartment of Medicine
Supervisor Dr. Gila Maor
Full Thesis textFull thesis text - English Version


Abstract

Articular hyaline cartilage covers the apical surfaces of the bones in synovial joints, enabling smooth gliding movements of the bones, and the ability to withstand high pressure and compression forces. Lesions of articular cartilage are common conditions and may develop as a result of several different factors such as trauma or as age-related tissue deterioration.

As articular hyaline cartilage does not heal spontaneously and has very little regenerative capacity, active therapeutic approaches are required to treat such articular damage. Due to the unique physico-mechanical properties of hyaline cartilage, it can only be replaced by natural hyaline cartilage tissue and not by an artificial substitute. As a result, many orthopedic as well as tissue engineering technologies have been explored in an effort to rehabilitate damage to cartilage in articular joints. Unfortunately, the end results of these attempts have been impeded by the inherent tendency of implanted cartilage cells to dedifferentiate into fibroblast-like cells, producing a stiff fibrocartilage rather than a flexible hyaline cartilage.

We propose the use of a unique growth center, the mandibular condyle (MC), which serves as the growth center of the mandible during fetal and early post-natal life and unlike growth centers of long bones that are eventually replaced with bone tissue, the mandibular condyle cartilage never disappears. Since the the early post-natal mandibular condyle is a potential xenogeneic source, we used the pig xenogeneic model, as a cell-source. Using an in vitro model, we demonstrated that mandibular condyle-derived chondrocytes (MCDC) spontaneously differentiate into hyaline cartilage-producing cells, generating proper hyaline cartilage, which is implantable as a continuous carrier membrane (denoted CartiMove).

Screening CartiMove for safety parameters indicated that it exhibits no immunogenic or pathogenic risks in xenotransplantation. Additionally, when employing an in vivo model of xenotransplantation in goats, we established that CartiMove rehabilitates damaged articular cartilage, filling the lesion with a non-fibrotic hyaline cartilage  tissue. Hence, we conclude that our model for spontaneously differentiating hyaline cartilage cells, derived from the mandibular condyle of a neonatal mammal, may serve as a reliable solution for the restoration of damaged articular cartilage.

Finally, in attempts to minimize the surgical procedure of the implantation, we  developed a rigid hyaline patch, designed to be implanted arthroscopically, in which MCDCs are adhered to a biodegradable carrier membrane, denoted Cartistick.

Screening proliferation and differentiation activities of the cartilaginous component of Cartistick, indicate that the cells maintain their chondrogenic cascade and may serve as an easily implantable cartilage tissue.