Vocal fold restoration after scarring: biocompatibility and efficacy of an MSC-based bioequivalent.

BACKGROUND: There is growing interest to application of regenerative medicine approaches in otorhinolaryngological practice, especially in the framework of the therapy of vocal fold (VF) scar lesions. The used conservative and surgical methods, despite the achieved positive outcomes, are frequently unpredictable and do not result in the restoration of the VF's lamina propria's structure, which provides the mechanical properties necessary for vibration. In this connection, the aim of this study was to ascertain the safety and efficacy of a bioequivalent in the treatment of VF scars using a rabbit model of chronic damage. METHODS: The bioequivalent consisted of a hydrogel system based on a PEG-fibrin conjugate and human bone marrow-derived MSC. It was characterized and implanted heterotopically into rats and orthotopically into rabbits after VF scar excision. RESULTS: We showed that the fabricated bioequivalent consisted of viable cells retaining their metabolic and proliferative activity. While being implanted heterotopically, it had induced the low inflammatory reaction in 7 days and was well tolerated. The orthotopic implantation showed that the gel application was characterized by a lower hemorrhage intensity (p = 0.03945). The intensity of stridor and respiratory rate between the groups in total and between separate groups had no statistically significant difference (p = 0.96 and p = 1; p = 0.9593 and p = 0.97…1, respectively). In 3 days post-implantation, MSC were detected only in the tissues closely surrounding the VF defect. The bioequivalent injection caused that the scar collagen fibers were packed looser and more frequently mutually parallel that is inherent in the native tissue (p = 0.018). In all experimental groups, the fibrous tissue's ingrowth in the adjacent exterior muscle tissue was observed; however, in Group 4 (PEG-Fibrin + MSC), it was much less pronounced than it was in Group 1 (normal saline) (p = 0.008). The difference between the thicknesses of the lamina propria in the control group and in Group 4 was not revealed to be statistically significant (p = 0.995). The Young's modulus of the VF after the bioequivalent implantation (1.15 ± 0.25 kPa) did not statistically significantly differ from the intact VF modulus (1.17 ± 0.45 kPa); therefore, the tissue properties in this group more closely resembled the intact VF. CONCLUSIONS: The developed bioequivalent showed to be biocompatible and highly efficient in the restoration of VF's tissue.

A New Method for Plastic Closure of an Extensive Laryngotracheal Defect.

Introduction: Elimination of extensive defects of the larynx and trachea by using musculoskeletal plastics without the use of supporting materials is not always sufficient. Laser modeling of cartilage tissue is a promising technique in modern medicine. Case Report: This article presents a new method for plastic closure of an extensive defect in the larynx and trachea with the help of costal auto-cartilage modeled by an erbium fiber laser with wavelength of 1.56 µm. Conclusions: The presented method allows us to restore the anatomical integrity of the respiratory tract at the final stage of surgical treatment of patients with chronic combined laryngeal and tracheal stenosis. Presented own clinical observation.

Laser reshaping of costal cartilage for transplantation.

BACKGROUND AND OBJECTIVE: Laser reshaping of cartilage is a new effective and safe technique for correction of nasal septum and ear deformities. Costal cartilage is a most suitable natural material for transplantation. The problem is to obtain stable proper shape of cartilage implants. The objective of this article is to study reshaping of porcine costal cartilage for larynx stenosis surgery using Erbium glass fiber laser. MATERIALS AND METHODS: Porcine cartilage plates 3 mm in thickness were mechanically curved and irradiated (1) on one side (stretched or compressed) and (2) on both sides with different sequence. Irradiation was performed using a 1.56 µm laser with power varied from 1 to 2.5 W, exposure time from 5 to 20 seconds, spot diameter of 2.5 mm, pulse duration of 500 milliseconds, pulse repetition rate of 1.4 Hz. For each laser setting, stable curvature radius was measured during 24 hours after the experiment. Irradiated samples were analyzed by means of differential scanning calorimerty (DSC) to reveal the collagen denaturation degree. RESULTS: The optimum laser setting for stable reshaping of costal cartilage without visual thermal damage of cartilage matrix was established: laser power of 2.2 W, exposure time of 6 seconds. Nonlinear thermomechanical behavior of cartilage in the course of its laser reshaping is experimentally revealed. The influence of irradiation sequence on the curvature radius of cartilage implant is found for the first time. It is shown that (1) it is possible to use laser reshaping technique for making stable proper shape of costal cartilage, and (2) primary irradiation of compressed side followed with an irradiation of stretched side is more effective than reverse sequence of laser treatment. DSC analysis showed that thermal effect of irradiated specimens (2.58-3.79 J/g) was slightly lower that that for intact cartilage specimens and considerably lower than that for denaturation of collagen (65 ± 5 J/g). CONCLUSIONS: It is possible to use laser reshaping technique for preparation of stable cartilage implants. Nonlinear thermomechanical behavior of cartilage is experimentally revealed. The influence of irradiation sequence on curvature radius of cartilage grafts is established for the first time.