Update on Cartilage Regeneration and Clinical Applications of Tissue Engineering in the Management of Cartilage Defects

Abstract

The limited repair potential of human articular cartilage results in the eventual development of osteoarthritis, and remains a significant clinical and economic challenge throughout the world. Cartilage regeneration has evolved from palliative methods, such as débridement and lavage or abrasion chondroplasty, to what has been named the two "R" paradigm: repair and replacement. Replacement aims to restore the contour of the articular surface by replacing a lesion in it with an osteochondral graft, whether autogenous, allogenous, or synthetic. Repair involves stimulating the formation of a biologic tissue that fills the defect in the articular surface. This initially involved marrow-stimulation techniques, including microfracture, which remains the most popular procedure for cartilage repair and is considered the standard of care for small cartilage defects because of its simple technique, cost-effectiveness, and single-stage nature. More recently, other cartilage repair strategies have evolved through modifications of bone marrow stimulation and the implementation of tissue-engineering strategies. The development of cartilage-regeneration strategies based on tissue engineering has progressed to provide a more functional biologic tissue for damaged cartilage. Currently, cartilage regeneration has three cornerstones. First, it requires a cell population capable of proliferation and differentiation into mature chondrocytes. Second, it requires a scaffold that is chondro-conductive and/or chondro-inductive. Third, it requires the introduction of growth factors and signaling molecules that stimulate the cellular response and subsequent production of a hyaline extracellular matrix composed predominantly of type II collagen and aggrecan. Numerous limitations hinder the translation of these applications from basic science to clinical research. The most important of these are potential contamination and disease transmission after the manipulation in vitro of cell lineages. Also important are the optimal dosage and delivery of growth factors for the initiation of chondrogenesis and maintenance of the resulting cartilage. This article summarizes the advances that have been made in cartilage regeneration, with their clinical applications and results. Specific emphasis is given to the knee and ankle joints because they remain the two most common joints for the implementation of cartilage-regeneration procedures in clinical practice.

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