PROJECT SUMMARY/ABSTRACT:
Voice disorders are among the most common communication disorders across the lifespan. Approximately 3-
9% of the general population, including children and adults, have a voice problem at any given point in time. Our
ultimate aim is the permanent repair of injured, altered or dysfunctional vocal fold tissue using injected or printed
biomaterials for lesion-specific application. Much previous work on injectable biomaterials for VF repair has
targeted sub-epithelial injections through a needle. Such delivery method is useful for the surgical treatment of
pathologies allowing needle injection into the native LP, or into the muscle for VF medialization. We have
developed composite bioactive tissue-engineered biomaterials, namely glycol-chitosan (GCS) hydrogels with
imbedded collagen fibers (COL I+III. Within the past year, our group has refined the composition of the GCS
hydrogel to a highly porous viscoelastic hydrogel (PVH). The increased porosity of PVH is expected to enhance
infiltration and survival of host cells and thus accelerate endogenous tissue regeneration. We have completed a
series of in vitro experiments using an injectable form of PVH.
We propose to build novel bioprinting tools that can deliver biomaterials to dress wounds on site. When large
lesions such as cancer are surgically removed using cold knifes or lasers, large voids are created possibly all
the way through the LP, down to the muscle. Novel materials that cure, adhere and seal quickly in situ will be
developed to prevent being dislodged and ingested into the airway. We propose a fast polymerization material,
PVH-prt, that cures in seconds, as opposed to minutes, and that can be printed on site through a laryngoscope
using needle-sized nozzles. On-site layer-by-layer deposition and sculpting would rebuild the resected portion
of the VF using new materials that are mechanically tough, with high adhesive strength, and that solidify quickly.
We will investigate strategies to lay such implants using additive manufacturing tools that are based on
microfluidics. We will test custom-made endoscopic size surgical “3D printing pens” using ex vivo larynges and
VF replicas. We will perform pilot studies of this novel concept in vivo using an animal model.
We will evaluate our biomaterials in rabbits. Foreign body response, tissue viscoelasticity and phonatory
functions will be evaluated with histology, mechanical tests and flow-bench experiments, respectively. To
complement the known limitations of animal studies and build on previous studies, a phonomimetic bioreactor
will be used to systematically vary scaffold properties, types and phonation conditions, and assess the
mechanical characteristics of the engineered lamina propria. Our overarching goal is to translate these new
biomaterials and bioprinting tools into otolaryngology clinics in the United States and Canada within the next 5
years.
