Vocal cord tissue engineering: Pre-clinical scale-up

点击翻译按钮获取中文摘要

Veterans suffering loss of the larynx's vocal fold cover due to trauma or laryngeal cancer can suffer disabling voice difficulties, and treatment options are limited. A vibrating replacement tissue would revolutionize the treatment of laryngeal disorders. The work described in this proposal characterizes and optimizes a tissue-engineered Cell-based Outer Vocal cord Replacement (COVR). Adult human multipotent cells isolated from adipose tissue are cultured within fibrin hydrogel derived from the blood product cryoprecipitate. The result is a completely autologous three-dimensional tissue substitute. Upon implantation in rabbits, this construct healed well and produced normal short-term vibration for voicing. The COVR construct will now be introduced in a large animal model in preparation for human translation. This proposed research will assess the feasibility, safety, and efficacy of the tissue-engineered implant. Mechanisms of action will also be assessed by determining the fate of the implanted cells, and the effect on extracellular matrix and inflammation. Human cells will be implanted with immunosuppression. A canine model is planned because extensive prior laryngeal work has been performed in canines, providing ample data on normal phonation. If canines are impossible, a porcine model would also allow scale-up to large mammals and detailed study of the wound healing. Completion of the proposed research will determine whether the COVR meets safety and efficacy requirements to proceed with a larger trial. The goal is to restore normal voicing without adverse events. If successful outcomes occur in this pilot study, a larger trial will be performed with the intention of generating pre-clinical data for FDA application.