Evaluation of Bioprinted Autologous Cartilage Grafts in an Immunocompetent Rabbit Model

The gold standard of auricular reconstruction involves manual graft assembly from autologous costal cartilage. The intervention may require multiple surgical procedures and lead to donor-site morbidity, while the outcome is highly dependent on individual surgical skills. A tissue engineering approach provides the means to produce cartilage grafts of a defined shape from autologous chondrocytes. The use of autologous cells minimizes the risk of host immune response; however, factors such as biomaterial compatibility and in vitro maturation of the tissue-engineered (TE) cartilage may influence the engraftment and shape-stability of TE implants. Here, this work tests the biocompatibility of bioprinted autologous cartilage constructs in a rabbit model. The TE cartilage is produced by embedding autologous auricular chondrocytes into hyaluronan transglutaminase (HATG) based bioink, previously shown to support chondrogenesis in human auricular chondrocytes in vitro and in immunocompromised xenotransplantation models in vivo. A drastic softening and loss of cartilage markers, such as sulfated glycosaminoglycans (GAGs) and collagen type II are observed. Furthermore, fibrous encapsulation and partial degradation of the transplanted constructs are indicative of a strong host immune response to the autologous TE cartilage. The current study thus illustrates the crucial importance of immunocompetent autologous animal models for the evaluation of TE cartilage function and compatibility. Auricular reconstruction is a complex process that involves grafting of autologous cartilage. Here, this work tests a tissue engineering (TE) approach to auricular reconstruction in a rabbit model. Autologous auricular chondrocytes were bioprinted and constructs were transplanted back to the animals. A strong host immune response to the autologous TE cartilage was observed, highlighting the importance of using immunocompetent animal models for the evaluation of TE grafts. image