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.

PROJECT NARRATIVE Voice problems constitute the most common communication disorder across the lifespan. Many malignant and benign vocal fold lesions require surgical removal using cold cutting tools or lasers, leaving a wound and in some cases a large void in the lamina propria and/or a tear in the epithelium. We are developing novel biomaterials that can be injected or deposited layer by layer into the wound site to help vocal fold tissue healing and promote the permanent regeneration of engineered tissue with the same viscoelasticity and morphology than the native uninjured lamina propria. These materials and tools would help patients with vocal fold injuries to completely recover their voice, with less hoarseness or dysphonia.