Abstract
Children suffering from microtia have few options for auricular reconstruction. Tissue engineering approaches attempt to replicate the complex anatomy and structure of the ear with autologous cartilage but have been limited by access to clinically accessible cell sources. Here we present a full-scale, patient-based human ear generated by implantation of human auricular chondrocytes and human mesenchymal stem cells in a 1:1 ratio. Additional disc construct surrogates were generated with 1:0, 1:1, and 0:1 combinations of auricular chondrocytes and mesenchymal stem cells. After 3 months in vivo, monocellular auricular chondrocyte discs and 1:1 disc and ear constructs displayed bundled collagen fibers in a perichondrial layer, rich proteoglycan deposition, and elastin fiber network formation similar to native human auricular cartilage, with the protein composition and mechanical stiffness of native tissue. Full ear constructs with a 1:1 cell combination maintained gross ear structure and developed a cartilaginous appearance following implantation. These studies demonstrate the successful engineering of a patient-specific human auricle using exclusively human cell sources without extensive in vitro tissue culture prior to implantation, a critical step towards the clinical application of tissue engineering for auricular reconstruction.
Highlights
For over two decades, tissue engineering the human auricle, or external ear, has been pursued as an alternative to existing methods of auricular reconstruction [1]
Human auricular chondrocytes (AuCs) were expanded through third passage (P3) before being encapsulated within engineered constructs
The data from this study show that engineered constructs fabricated using a 1:1 ratio of human AuCs and mesenchymal stem cells (MSCs) generated cartilage in vivo that was equivalent to native auricular cartilage and constructs containing solely AuCs, whereas constructs with only MSCs failed to generate cartilage tissue
Summary
Tissue engineering the human auricle, or external ear, has been pursued as an alternative to existing methods of auricular reconstruction [1]. The current gold standard treatment for patients with significant deformation or damage of the auricle is autologous reconstruction using costal cartilage. This is a complex surgical technique employed by relatively few surgeons due to morbidity at the rib cartilage donor site and challenges in producing auricles with acceptable aesthetic results [2,3,4]. There are reports of successful reconstruction using prosthetic scaffolds, widespread adoption of this approach has been limited by poor biocompatibility and potential for extrusion [3].
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