Articular cartilage defects of the knee pose significant challenges due to limited healing potential and a tendency to progress to osteoarthritis (OA). Traditional regenerative techniques are often costly and insufficient for treating osteochondral lesions, leading to a shift toward innovative cell-free treatments. Among these innovative therapies, one has been gaining particular attention. This chapter aims to illustrate the scientific evidence surrounding Agili-C™, exploring its composition, scientific rationale, clinical indications, and long-term efficacy. Composed of aragonite, Agili-C™ is able to support both articular cartilage and subchondral bone regeneration. While preclinical studies demonstrated its effectiveness, early human trials confirmed significant clinical outcomes and a favorable safety profile. The scaffold’s design facilitates easy handling, eliminates donor site morbidity, and allows for one-step procedures, making it a cost-effective solution. Mid-term follow-up studies reported a statistically significant improvement in clinical scores at the 1-, 2-, and 3-year follow-ups compared to baseline. The Agili-C® scaffold represents a promising advancement in treating knee cartilage defects, particularly in young patients and those with post-traumatic lesions, offering a comprehensive approach that addresses both chondral and osteochondral defects.