M S Courey1. 1. Vanderbilt Bill Wilkerson Center for Otolaryngology & Communication Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37212, U.S.A.
Abstract
OBJECTIVES/HYPOTHESIS: Dysphonia resulting from failure of glottic closure during voicing is a difficult clinical problem. Recently developed homologous collagen compounds may be beneficial in treating this problem. The objectives of this thesis are to: 1) evaluate the potential site(s) of collagen graft placement in the human vocal fold, quantify the amount of graft material that can be injected into these sites, and determine how these sites are accessed by the currently available surgical tools for injection; 2) determine the effects of the superficial vocal fold implant on laryngeal vibratory patterns and characterize how the implant affects the forces required to bring vocal folds into an adducted position for vibration; and 3) evaluate the host response to two different forms of cadaveric collagen. STUDY DESIGN: Prospective laboratory. METHODS: Three separate experiments were undertaken: 1) Eight cadaver larynges were injected with collagen compounds through a 27-gauge needle. The amount of substance required to medialize the vocal fold and potential positions for graft placement were evaluated. 2) Six cadaver larynges were mounted on a stabilizing stand while airflow, vocal fold length, adduction forces, and abduction forces on the vocal folds were manipulated. Vibratory patterns before and after the injection of the vocal folds with solubilized collagen were assessed. 3) A nude mouse model was used to study the host response to two different exogenous collagen compounds. RESULTS: Solubilized collagen compounds could be injected reliably into the superficial layer of the lamina propria (SLLP), medial portion of the thyroarytenoid muscle, or lateral portion of the thyroarytenoid muscle. When injected superficially, significantly less material was required to displace the medial edge of the vocal fold to midline (P =.0001). When graft material was placed into the medial portion of the thyroarytenoid (TA) muscle, the forces required to bring the vocal fold into a position suitable for vibration were significantly reduced (P =.0106) and the vibratory patterns of the vocal folds were not impaired. Both AlloDerm(R) and Dermalogen(R) solubilized preparations of human dermal tissue were well tolerated in the nude-mouse model. Minimal inflammatory reaction occurred. Small amounts of graft material were identified histologically at the end of the 6-month study period. The graft material appeared organized and had been infiltrated with fibroblasts of host origin. CONCLUSIONS: Homologous collagen compounds can be reliably injected into the cadaveric human larynx. When the substances are injected into the medial portion of the TA muscle, immediately deep to the vocal ligament, they decrease the force of contraction needed to bring the vocal folds into a position adequate for phonation and have minimal affect on the vibratory patterns. These forms of homologous collagen are well tolerated. A small amount persists over a 6-month interval. These materials warrant further clinical trials in human subjects.
OBJECTIVES/HYPOTHESIS: Dysphonia resulting from failure of glottic closure during voicing is a difficult clinical problem. Recently developed homologous collagen compounds may be beneficial in treating this problem. The objectives of this thesis are to: 1) evaluate the potential site(s) of collagen graft placement in the human vocal fold, quantify the amount of graft material that can be injected into these sites, and determine how these sites are accessed by the currently available surgical tools for injection; 2) determine the effects of the superficial vocal fold implant on laryngeal vibratory patterns and characterize how the implant affects the forces required to bring vocal folds into an adducted position for vibration; and 3) evaluate the host response to two different forms of cadaveric collagen. STUDY DESIGN: Prospective laboratory. METHODS: Three separate experiments were undertaken: 1) Eight cadaver larynges were injected with collagen compounds through a 27-gauge needle. The amount of substance required to medialize the vocal fold and potential positions for graft placement were evaluated. 2) Six cadaver larynges were mounted on a stabilizing stand while airflow, vocal fold length, adduction forces, and abduction forces on the vocal folds were manipulated. Vibratory patterns before and after the injection of the vocal folds with solubilized collagen were assessed. 3) A nude mouse model was used to study the host response to two different exogenous collagen compounds. RESULTS: Solubilized collagen compounds could be injected reliably into the superficial layer of the lamina propria (SLLP), medial portion of the thyroarytenoid muscle, or lateral portion of the thyroarytenoid muscle. When injected superficially, significantly less material was required to displace the medial edge of the vocal fold to midline (P =.0001). When graft material was placed into the medial portion of the thyroarytenoid (TA) muscle, the forces required to bring the vocal fold into a position suitable for vibration were significantly reduced (P =.0106) and the vibratory patterns of the vocal folds were not impaired. Both AlloDerm(R) and Dermalogen(R) solubilized preparations of human dermal tissue were well tolerated in the nude-mouse model. Minimal inflammatory reaction occurred. Small amounts of graft material were identified histologically at the end of the 6-month study period. The graft material appeared organized and had been infiltrated with fibroblasts of host origin. CONCLUSIONS: Homologous collagen compounds can be reliably injected into the cadaveric human larynx. When the substances are injected into the medial portion of the TA muscle, immediately deep to the vocal ligament, they decrease the force of contraction needed to bring the vocal folds into a position adequate for phonation and have minimal affect on the vibratory patterns. These forms of homologous collagen are well tolerated. A small amount persists over a 6-month interval. These materials warrant further clinical trials in human subjects.