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

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 unpredictabl...

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Published in:	Stem cell research & therapy Vol. 14; no. 1; p. 303
Main Authors:	Svistushkin, Mikhail, Shpichka, Anastasia, Bikmulina, Polina, Fayzullin, Alexey, Zolotova, Anna, Kosheleva, Nastasia, Selezneva, Liliya, Shavkuta, Boris, Lobacheva, Viktoria, Nikiforova, Anna, Kochetkov, Peter, Kotova, Svetlana, Starostina, Svetlana, Shekhter, Anatoly, Svistunov, Andrey, Svistushkin, Valeriy, Timashev, Peter
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 21-10-2023 BioMed Central BMC
Subjects:	Analysis Animals Biocompatibility Body fat Bone marrow Cicatrix - pathology Cicatrix - therapy Collagen Fibrin Hemorrhage Humans Hyaluronic acid Hydrogels Inflammation Lamina propria Mechanical properties Mesenchymal Stem Cell Transplantation Mesenchymal stromal cells Otolaryngology Polyethylene glycol Rabbits Rats Regenerative Medicine Respiration Scarring Scars Spectrum analysis Statistical analysis Stem cells Tissue engineering Viscoelasticity Vocal Cords Vocal folds Vocal organs Germany United States > US Russia Fibrin In vivo Regenerative medicine Tissue engineering Vocal folds PEG-fibrin Mesenchymal stromal cells Bioequivalent Scarring
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Summary:	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. 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. 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. The developed bioequivalent showed to be biocompatible and highly efficient in the restoration of VF's tissue.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1757-6512 1757-6512
DOI:	10.1186/s13287-023-03534-x