Overcoming Clinical Challenges to Tissue Engineering the Human Auricle

Abstract

Autologous costal cartilage and alloplastic implant reconstruction for deformed or damaged auricles fail to accurately replicate the complex morphology of the ear or the structure, composition, or mechanics of auricular cartilage. Tissue engineering can provide patient-specific auricular replacements featuring robust auricular cartilage, but several challenges to clinical translation must first be addressed (‎Chapter 1). Advances in bioimaging and additive manufacturing technology have allowed for improved morphology following construct generation and have the potential to further the clinical transition by making tissue-engineered auricles more accessible, reproducible, and scalable (‎Chapter 2). The stability of an engineered ear following implantation is of critical importance to the clinical outcome. Long-term implantation of full-size pediatric auricles was performed to ascertain the development of a tissue-engineered ear (‎Chapter 3). Auricular chondrocytes (AuCs) have limited clinical accessibility, whereas mesenchymal stem cells (MSCs) can be acquired in large numbers with relatively minimal surgery. The capacity for MSCs to reduce AuC requirement for auricular cartilage tissue engineering was evaluated (‎Chapter 4 and Appendix A). The limits of AuC expansion without impairment of cartilage generating properties was also explored (‎Chapter 5). Finally, cell-seeded collagen hydrogel constructs consistently demonstrate contraction following implantation, negatively impacting construct morphology and amount of tissue generated. Low oxygen tensions similar to the state of native cartilage tissue were applied to AuCs during both expansion and three-dimensional culture to determine the effect on construct shape maintenance and cartilage development (‎Chapter 6). Collectively, this dissertation demonstrates the stability of patient-specific, tissue-engineered ears during in vivo growth, while also providing multiple avenues for clinical cell sourcing and a method for preventing changes in construct morphology (‎Chapter 7). This work shows the potential for tissue engineering as a superior option for auricular reconstruction and overcomes several of the obstacles towards clinical translation of this technique.