Scarring of even one of the paired vocal folds (Figure 1), which constitute the vocal apparatus, can result in voice changes ranging from hoarseness to complete voice loss. In this debilitating condition, the pliability of the vocal fold lamina propria is impaired and its physical volume is reduced. These alterations disrupt vibratory efficiency of the scarred vocal fold and reduce the quality of cycle-to-cycle closure of the paired vocal fold structures. Chronic lamina propria scar has proven difficult to treat with current surgical techniques or standard injectable fillers (e.g. collagen, fat). As such, researchers are actively exploring alternative treatment routes, including the development of designer implant biomaterials for functional lamina propria regeneration. Any biomaterial developed for restoration of chronic lamina propria scar must address both decreased pliability and volumetric deficiency of scarred lamina propria Long-term lamina propria augmentation and improvement in biomechanical properties following implant insertion requires local VFF to produce appropriate extracellular matrix (ECM) as the implant material degrades.
Lamina propria regeneration biomaterials are generally designed to elicit desired ECM production from VFF as the biomaterial degrades, with the rationale that appropriate ECM production will result in tissue with desired mechanical function. Although this approach has yielded significant advances, it fails to capture several aspects of the in vivo implant environment, which critically impact the quality and rate of VFF matrix synthesis. For instance, fibroblasts associated with chronic vocal fold scar display myofibroblastic or fibrotic phenotypes, whereas the VFF employed in most in vitro biomaterial studies are “normal” or non-fibrotic. In addition, biomaterial insertion/injection is associated with an acute inflammatory response where macrophages are induced to take on a classically-activated/pro-inflammatory wound-healing phenotype. We hypothesize that a biomaterial can be designed to contain bioactive moieties that induce local myofibroblasts to take on a normal VFF phenotype and induce local macrophages to alter their polarization to an anti-inflammatory, pro-tissue healing environment.
Video of Normal Vocal Fold Vibration:
Video of Scarred Vocal Fold Vibration: