In vivo comparison of biomimetic approaches for tissue regeneration of the scarred vocal fold

Abstract

The objective of this study was to determine if three different biomimetic approaches could facilitate tissue regeneration and improve viscoelastic properties in the scarred vocal fold lamina propria extracellular matrix (ECM). Twenty rabbit vocal folds were biopsied bilaterally; 2 months postinjury rabbits were unilaterally treated with (i) autologous fibroblasts, (ii) a semisynthetic ECM (sECM), or (iii) autologous fibroblasts encapsulated in sECM. Saline was injected as a control into the contralateral fold. Animals were sacrificed 2 months after treatment. Outcomes measured were procollagen, collagen, and fibronectin levels in the lamina propria, and tissue viscosity and elasticity across three frequency decades. All treatment groups demonstrated accelerated proliferation of the ECM. Vocal fold lamina propria treated with autologous fibroblasts were found to have significantly improved viscosity (p = 0.0077) and elasticity (p = 0.0081) compared to saline. This treatment group had significantly elevated fibronectin levels. sECM and autologous fibroblasts/sECM groups had significantly elevated levels of procollagen, collagen, and fibronectin, indicating abundant matrix production as compared to saline with viscoelastic measures that did not differ statistically from controls. The use of autologous fibroblasts led to better restoration of the vocal fold lamina propria biomechanical properties. Optimization of cell-scaffold interactions and subsequent cell behavior is necessary for utilization of scaffold and scaffold-cell approaches.

FIG. 1.

Histological levels for (A) procollagen, (B) collagen, and (C) fibronectin for four conditions—saline treated, autologous fibroblast treated, sECM treated, and sECM/autologous fibroblast treated. *p < 0.05 compared to saline treated; **p < 0.05 compared to sECM; ***p < 0.05 compared to autologous fibroblast treated.

FIG. 2.

(A) Elastic modulus (G′) and (B) viscous modulus (G″) for four conditions—saline treated, autologous fibroblast treated, sECM treated, and sECM/autologous fibroblast treated.