In recent years, the search for novel and biocompatible sources for cartilage tissue engineering has become a key focus in regenerative medicine. Given the limitations of mammalian tissues and the demand for naturally structured biomaterials, marine-derived sources have gained increasing scientific attention. Among these, the cartilage of cartilaginous fish offers unique cellular and extracellular characteristics that may position it as a promising alternative scaffold for cartilage regeneration. The aim of this work was to consider the hystomorphological characteristics of backbone cartilage from fish with a cartilaginous skeleton, including reticulate whipray, milk shark and beluga sturgeon for potential application in cartilage tissue engineering. Through detailed histological and immunohistochemical evaluation of cartilage from three fish species, significant differences in cellular and extracellular matrix composition were identified. Histomorphometric analysis demonstrated that the number of chondrocytes was markedly higher in the reticulate whipray and milk shark compared to the beluga sturgeon (p < 0.05), indicating species-dependent variations in cellular density that may influence tissue regeneration potential. Moreover, glycosaminoglycan (GAG) content was highest in the whipray cartilage (p < 0.05), reflecting the presence of a rich proteoglycan matrix essential for maintaining cartilage hydration and mechanical resilience. Analysis of collagen content analysis revealed that whipray and beluga cartilage had greater total collagen than shark cartilage (p < 0.05), suggesting that structural protein composition also varies considerably among species. Immunohistochemistry for type II collagen (Col II) demonstrated that whipray cartilage exhibited the most abundant Col II among the species, indicative of a more hyaline-like phenotype and therefore a more desirable microstructure for tissue engineering purposes. These histological findings highlight the favorable microstructure of whipray cartilage, characterized by high chondrocyte density, abundant GAGs, and strong type II collagen expression, making it especially promising as a scaffold material in cartilage tissue engineering
