In Vitro Regeneration of Patient-specific Ear-shaped Cartilage and Its First Clinical Application for Auricular Reconstruction

TLDR

Microtia is a congenital ear malformation that impairs well‑being, and although tissue‑engineered ear‑shaped cartilage has been successfully regenerated in a nude mouse, technical challenges have prevented clinical use. Patient‑specific ear‑shaped cartilage was engineered in vitro by expanding microtia chondrocytes on a compound biodegradable scaffold and cultured, followed by surgical trials to optimize graft handling. The engineered cartilage was successfully implanted in five microtia patients, yielding satisfactory aesthetics and mature cartilage after 2.5 years, marking a breakthrough in clinical translation. The study was registered in the Chinese Clinical Trial Registry (ChiCTR‑ICN‑14005469).

Abstract

Microtia is a congenital external ear malformation that can seriously influence the psychological and physiological well-being of affected children. The successful regeneration of human ear-shaped cartilage using a tissue engineering approach in a nude mouse represents a promising approach for auricular reconstruction. However, owing to technical issues in cell source, shape control, mechanical strength, biosafety, and long-term stability of the regenerated cartilage, human tissue engineered ear-shaped cartilage is yet to be applied clinically. Using expanded microtia chondrocytes, compound biodegradable scaffold, and in vitro culture technique, we engineered patient-specific ear-shaped cartilage in vitro. Moreover, the cartilage was used for auricle reconstruction of five microtia patients and achieved satisfactory aesthetical outcome with mature cartilage formation during 2.5 years follow-up in the first conducted case. Different surgical procedures were also employed to find the optimal approach for handling tissue engineered grafts. In conclusion, the results represent a significant breakthrough in clinical translation of tissue engineered human ear-shaped cartilage given the established in vitro engineering technique and suitable surgical procedure.This study was registered in Chinese Clinical Trial Registry (ChiCTR-ICN-14005469).