Tissue Engineered Human Elastic Cartilage From Primary Auricular Chondrocytes for Ear Reconstruction

ABSTRACT Functional elastic cartilage remains an unmet challenge in regenerative medicine, limiting reconstructive options for children born with microtia, the congenital malformation of the auricle. The current gold standard treatment relies on harvesting rib cartilage, an invasive procedure associated with donor site morbidity, impaired aesthetics, and unnaturally stiff ears due to the use of hyaline cartilage. Here, we engineered primary human auricular chondrocytes to generate functional elastic cartilage with near‐native tissue properties. This was achieved through the synergistic integration of growth factor‐controlled chondrogenesis, stress‐relaxing biomaterials that promote elastic cartilage formation, and a bioreactor platform enabling homogeneous tissue maturation. The engineered grafts exhibited a uniform extracellular matrix composition with elastin, glycosaminoglycans, and collagen II comparable to native auricular cartilage, while lacking the fibrocartilage marker collagen I. The resulting tissue achieved a compressive modulus of 1.1 ± 0.03 MPa, matching native cartilage (1.0 ± 0.1 MPa), and maintained its structural integrity and elasticity in vivo for 6 weeks in a subcutaneous rat model. These grafts represent the closest replication of native human elastic cartilage achieved ex vivo to date, establishing a foundation for clinically viable, functional auricular grafts.