SPHERpower: MSC spheroid-based bioequivalent lead to the efficient restoration of the scarred vocal folds.

Cell-based therapy has become an attractive option to restore the vocal folds (VF) after scarring. Despite that first clinical trials using mesenchymal stromal cells (MSC) suspension has been launched, there is still an issue of retaining cells at implantation site to prolong their effects. Therefore, cell spheroids are considered to be a part of next generation bioequivalents. This study aims to reveal the safety and efficacy of MSC spheroid-based bioequivalent in treating VF scars in comparison with cell suspension. To evaluate this approach in vivo, a rabbit vocal fold scar model was established in 48 male rabbits, which were allocated to four groups: untreated control, PEG-fibrin, PEG-fibrin with MSC suspension, and PEG-fibrin with MSC spheroids. In 3 months post operation, in group where the MSC suspension-based bioequivalent was implanted, the mature connective tissue was located beneath the epithelium without dystrophic changes and had a relatively loose ECM; the thickness of the lamia propria was higher than that in the intact VF. In group where we used the MSC spheroid-based bioequivalent the loose connective tissue consisted of longitudinally oriented collagen fibers, spindle-shaped fibroblasts; the lamia propria was relatively thin (116.42 ± 42.77 μm) and loose and did not differ from the intact VF. Both types enabled the VF restoration; nevertheless, the use of MSC spheroids lead to more efficient regeneration: the tissue architectonics and mechanical properties of the treated VF was more similar to those of the intact VF.