Tissue engineering the human auricle by auricular chondrocyte-mesenchymal stem cell co-implantation

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.

Tissue engineering applications in otolaryngology—The state of translation

“…Heatmap representing the proportion of publications by year that utilized specific translational research methodologies from construct characterization to human trial to investigate otologic tissue engineering 15,25‐35,38‐43,45,46,107‐144 …”

Coating Medpor® Implant with Tissue-Engineered Elastic Cartilage

“…Cohen et al demonstrated the successful outcome of patient-specific human ear cartilage engineered exclusively with human cell sources without extensive in vitro cell expansion prior to implantation. This study was a critical step towards the clinical application of tissue engineering for ear cartilage reconstruction [27].…”

Cartilage tissue engineering for craniofacial reconstruction

“…Several trials showed that a mixture of auricular chondrocytes and MSCs yielded cartilage that was equivalent to constructs made from solely chondrocytes. The ratio of chondrocytes and MSCs varied from 1:1 to 1:3 [76,77] . A recent clinical trial of microtia reconstruction with tissueengineered cartilage was published in 2018 [78].…”

“…The reconstructed external ear maintained its shape up to 2 years. The progress of human auricular cartilage tissue engineering is summarized in Table 4 [70][71][72][73][74][75][76][77][78][79].…”