De novo tissue formation using custom microporous annealed particle hydrogel provides long-term vocal fold augmentation

Abstract

Biomaterial-enabled de novo formation of non-fibrotic tissue in situ would provide an important tool to physicians. One example application, glottic insufficiency, is a debilitating laryngeal disorder wherein vocal folds do not fully close, resulting in difficulty speaking and swallowing. Preferred management of glottic insufficiency includes bulking of vocal folds via injectable fillers, however, the current options have associated drawbacks including inflammation, accelerated resorption, and foreign body response. We developed a novel iteration of microporous annealed particle (MAP) scaffold designed to provide persistent augmentation. Following a 14-month study of vocal fold augmentation using a rabbit vocal paralysis model, most MAP scaffolds were replaced with tissue de novo that matched the mixture of fibrotic and non-fibrotic collagens of the contralateral vocal tissue. Further, persistent tissue augmentation in MAP-treated rabbits was observed via MRI and via superior vocal function at 14 months relative to the clinical standard.

Cell-scale porosity in microporous annealed particle (MAP) scaffolds modulates immune response and promotes formation of innervated muscle fibers in volumetric muscle loss injuries

“…Here, we explore the treatment of VML injuries with Microporous Annealed Particle (MAP) scaffolds, which are injectable hydrogel constructs that start as a slurry of spherical microgels that become bonded together (i.e., annealed) in situ to form a structurally stable scaffold with cell-scale porosity. This biomaterial platform has been used for multiple regenerative engineering applications, including dermal wound healing 54, 55 , brain recovery from stroke 56, 57 , cardiac muscle recovery following myocardial infarction 58 , vocal fold augmentation 59, 60 , acute cartilage defect healing 61 , recovery from spinal cord injury 62 , and delivery of mesenchymal stem cells 63 . Additionally, previous work has shown that MAP scaffold porosity has immunomodulatory properties, as demonstrated by their lack of fibrous encapsulation 60, 64 , mitigation of glial scarring 57, 62 , and decreased presence of immune cells with inflammatory phenotypes 54, 57, 62, 65 .…”

“…This biomaterial platform has been used for multiple regenerative engineering applications, including dermal wound healing 54, 55 , brain recovery from stroke 56, 57 , cardiac muscle recovery following myocardial infarction 58 , vocal fold augmentation 59, 60 , acute cartilage defect healing 61 , recovery from spinal cord injury 62 , and delivery of mesenchymal stem cells 63 . Additionally, previous work has shown that MAP scaffold porosity has immunomodulatory properties, as demonstrated by their lack of fibrous encapsulation 60, 64 , mitigation of glial scarring 57, 62 , and decreased presence of immune cells with inflammatory phenotypes 54, 57, 62, 65 . We tested the potential of acellular MAP scaffolds to address many of the challenges of regeneration after a VML injury in a rodent model, evaluating the effect of microporosity specifically by comparing MAP scaffolds to nanoporous bulk scaffolds with the same chemical composition and stiffness.…”