3D bioprinted composite scaffold incorporating microfluidics-derived chondrocyte microspheroids promotes auricular cartilage regeneration

Microtia remains a major clinical challenge, as autologous costal cartilage transplantation-the current gold standard-suffers from donor-site morbidity and imprecise morphology, whereas synthetic implants are prone to immune rejection and structural collapse. Here, we present a biphasic composite strategy integrating microfluidics and 3D bioprinting. Organoid-like auricular spheroids generated via microfluidics exhibited a biomimetic architecture, featuring cartilage-specific collagen cores surrounded by organized chondrocytes, with sustained ECM secretion and phenotype maintenance. These bioactive spheroids were subsequently incorporated into a biomimetic bioink and patterned through extrusion-based 3D bioprinting, enabling precise anatomical shaping and functional scaffold construction. Upon implantation in immunodeficient mice, the biphasic constructs promoted rapid in situ cartilage regeneration and ECM deposition, yielding tissue with morphological and histological features closely resembling native auricular cartilage. Collectively, this study demonstrates that the integration of microfluidic spheroids with 3D bioprinting offers a balanced solution between structural fidelity and biological functionality, providing a promising pathway for auricular cartilage reconstruction.