Articular cartilage repair biomaterials: strategies and applications Articular cartilage injury is a common global health issue, requiring effective treatment. Due to the lack of blood vessels and nerves, cartilage has limited self-repair ability. Although various clinical treatments are available, unfavorable outcomes and complications remain prevalent. The emergence of tissue engineering and regenerative medicine has generated interest in using biomaterials for cartilage repair. However, comprehensive reviews of strategies and applications are limited. This review provides an overview of primary biomaterials and bioactive substances for cartilage repair, including regeneration, substitution, and immunization. The strategies include the use of mechanically supportive scaffolds, which influence cellular behavior, and bioactive substances such as bioactive factors, stem cells, extracellular vesicles, and cartilage organoids. Composite bioactive scaffolds produced for clinical use are also presented. This review offers innovative solutions for treating cartilage ailments and emphasizes the potential of biomaterials for cartilage repair in clinical translation. Articular cartilage injury is a prevalent global health issue, posing significant treatment challenges in orthopedics and sports medicine. In a study of 1000 patients undergoing knee arthroscopy, 61% exhibited cartilage or osteochondral pathology signs, and 19% had focal cartilage or osteochondral defects. Articular cartilage is a smooth, elastic, and translucent connective tissue that bears loads and reduces joint friction. In cases of cartilage injury, the first structural damage occurs in the cartilage surface layer, leading to the loss of proteoglycans in the extracellular matrix (ECM) and disrupting the collagen fiber network. Subsequently, chondrocytes degenerate and are lost, resulting in minor localized damage that may spread to the middle and deep layers of cartilage. Cartilage tissue has few cells, no blood vessels, lymph, or nerves, which restricts the ability to repair after injury. Poor cartilage damage treatment can cause degenerative arthritis, meniscus injury, bone hyperplasia, and other joint diseases. Several clinical techniques are available for treating cartilage injuries, including microfracture technology, osteochondral transplantation technology, autologous chondrocyte transplantation technology, and matrix-induced chondrogenesis technology. However, these techniques have significant limitations, such as the challenge of repairing large areas of injury, the immune response of the patient, and the limited availability of donor tissue. In arthroscopic techniques, progenitor cells are recruited from the bloodstream and bone marrow into the voids created by microdrilling or microfracture. While this approach promotes cartilage regeneration by inducing differentiation of these cells into chondrogenic phenotypes, it results in mechanically weak cartilage that often degenerates into severe osteoarthritis later on. Transplanting soft tissues like perichondrium and periosteum to full-thickness articular cartArticular cartilage repair biomaterials: strategies and applications Articular cartilage injury is a common global health issue, requiring effective treatment. Due to the lack of blood vessels and nerves, cartilage has limited self-repair ability. Although various clinical treatments are available, unfavorable outcomes and complications remain prevalent. The emergence of tissue engineering and regenerative medicine has generated interest in using biomaterials for cartilage repair. However, comprehensive reviews of strategies and applications are limited. This review provides an overview of primary biomaterials and bioactive substances for cartilage repair, including regeneration, substitution, and immunization. The strategies include the use of mechanically supportive scaffolds, which influence cellular behavior, and bioactive substances such as bioactive factors, stem cells, extracellular vesicles, and cartilage organoids. Composite bioactive scaffolds produced for clinical use are also presented. This review offers innovative solutions for treating cartilage ailments and emphasizes the potential of biomaterials for cartilage repair in clinical translation. Articular cartilage injury is a prevalent global health issue, posing significant treatment challenges in orthopedics and sports medicine. In a study of 1000 patients undergoing knee arthroscopy, 61% exhibited cartilage or osteochondral pathology signs, and 19% had focal cartilage or osteochondral defects. Articular cartilage is a smooth, elastic, and translucent connective tissue that bears loads and reduces joint friction. In cases of cartilage injury, the first structural damage occurs in the cartilage surface layer, leading to the loss of proteoglycans in the extracellular matrix (ECM) and disrupting the collagen fiber network. Subsequently, chondrocytes degenerate and are lost, resulting in minor localized damage that may spread to the middle and deep layers of cartilage. Cartilage tissue has few cells, no blood vessels, lymph, or nerves, which restricts the ability to repair after injury. Poor cartilage damage treatment can cause degenerative arthritis, meniscus injury, bone hyperplasia, and other joint diseases. Several clinical techniques are available for treating cartilage injuries, including microfracture technology, osteochondral transplantation technology, autologous chondrocyte transplantation technology, and matrix-induced chondrogenesis technology. However, these techniques have significant limitations, such as the challenge of repairing large areas of injury, the immune response of the patient, and the limited availability of donor tissue. In arthroscopic techniques, progenitor cells are recruited from the bloodstream and bone marrow into the voids created by microdrilling or microfracture. While this approach promotes cartilage regeneration by inducing differentiation of these cells into chondrogenic phenotypes, it results in mechanically weak cartilage that often degenerates into severe osteoarthritis later on. Transplanting soft tissues like perichondrium and periosteum to full-thickness articular cart