Challenges in Cartilage Tissue Engineering

Over 27 million Americans suffer from cartilage damage with several million people affected per year. Articular cartilage or hyaline cartilage has a limited capacity to heal after damage from injury or degenerative disease. In an attempt to delay the progression of widespread damage, orthopedic surgeons routinely treat osteochondral injuries with minimally invasive surgical procedures involving articular resurfacing. The knee is the most prevalent joint affected. One of the three most common treatments for injury of the knee is arthroscopic lavage, either with or without debridement. Yet this treatment is merely palliative, providing symptomatic relief but does not repair injury to cartilage [1]. The most frequently used reparative treatment for small symptomatic lesions of articular cartilage of the knee are marrow-stimulating techniques, such as subchondral drilling, abrasion arthroplasty and microfracturin [2]. In microfracturing, which is the most commonly used technique, multiple holes made in the subchondral bone allow bone marrow components to reach the joint surface and facilitate repair. Bone marrow contains mesenchymal stem cells that have the potential to form new cartilage. However, fibrocartilage typically forms, which is mechanically much less robust than articular cartilage. While it may provide pain mitigation, fibrocartilage typically shows signs of degeneration after one year [3,4]. Alternative surgical procedures include autologous chondrocyte transplantation and osteoarticular transfer. These procedures require harvesting cartilage from the patient or cadaveric source and later injecting/grafting into the lesion. In the past few years, three systematic reviews of current treatments for focal chondral defects have come to the same conclusion that no “gold standard” exists for repairing chondral injuries [2,5,6]. All current surgical interventions produce mediocre efficacy. Once degeneration has progressed to severe osteoarthritis (OA) where articular resurfacing is no longer an option, the only recourse is Total Knee Replacement (TKR). However, TKR is contraindicated for patients younger than 45-years old, for whom no alternative treatment exists. This younger patient population is increasing due to sports-related injuries and the growing obesity epidemic. Therefore, a growing unmet need exists for future interventions that dramatically delay or halt widespread cartilage damage.