Abstract
The construction and regeneration of tissue-engineered auricles are pacesetters in tissue engineering and have realized their first international clinical application. However, the unstable regeneration quality and insufficient mechanical strength have become significant obstacles impeding its clinical promotion. The perichondrium is indispensable for the nutritional and vascular supply of the underlying cartilage tissue, as well as for proper anatomical functioning and mechanical performance. This study presents a novel strategy for integrated construction of bioengineered perichondrium with bioprinted cartilage to enhance the regeneration quality and mechanical properties of tissue-engineered auricles. Simulating the anatomical structure of the native auricle designs a sandwich construction model containing bilateral perichondrium and intermediate cartilage, employing a photocrosslinkable acellular cartilage matrix and gelatin bionics matrix microenvironment, applying co-cultured auricular chondrocytes and adipose-derived stem cells creates functional cell populations, designing hatch patterns imitates microscopic arrangement structures, utilizing sacrificial materials forms interlaminar network traffic to enhance the tight connection between layers, and finally, assessing the regenerative quality of the constructs explores their feasibility and stability. The multi-level and multi-scale biomimetic construction strategy overcomes the technical limitation of the integrated construction of perichondrium-wrapped auricles and realizes biomimicry in morphology, structure, and biomechanics. Altogether, this study provides a technical reference for the hierarchical construction of complex tissues and promotes the clinical translation and application of engineered tissues or organs.