Regeneration of Paralyzed Vocal Fold by the Injection of Plasmid DNA Complex-Loaded Hydrogel Bulking Agent

Abstract

Various growth factor delivery systems were used in the treatment of glottal insufficiency; however, relatively little attention has been paid to a gene delivery system for aspects of active vocal fold (VF) regeneration. Herein, we present a plasmid DNA (pDNA; bFGF gene encoding) complex-loaded alginate (ALG)/hyaluronic acid (HA) mixture hydrogel dispersed with polycaprolactone (PCL) microspheres that can enhance simultaneous regeneration of VF muscle and lamina propria, as well as have a bulking effect on atrophied VF. We have demonstrated long-term efficacy of bFGF synthesized from pDNA complex-transfected cells in vitro. PCL microspheres–dispersed ALG/HA hydrogel (with or without pDNA complex loading) are injected into rabbit VFs with recurrent laryngeal nerve denervation. The PCL microspheres dispersed in the hydrogel bulking agents remain stable at the applied site, leading to constant medialization of the paralyzed VF without significant initial volume loss even after 24 weeks. A regenerative effect for collagen deposition and HA synthesis around the injected site, which are major components of VF tissue, is well confirmed in the pDNA-complex-loaded hydrogel group. Moreover, the compensation of atrophied VFs also leads to the contact of bilateral VF and the remarkable recovery of voice function in the pDNA-complex-loaded group. Based on the results, pDNA (bFGF encoding) complex-loaded hydrogel dispersed with PCL microspheres may be employed as a bioactive bulking agent for the treatment of glottal insufficiency.

Functional mechanism of AMPK activation in mitochondrial regeneration of rat peritoneal macrophages mediated by uremic serum

“…Chronic inflammatory diseases not only have a persistent pro-inflammatory response but also have the possibility of an uncontrolled inflammatory response [ 18 – 20 ]. It has been found that almost all kidney diseases are accompanied by secretion of inflammatory factors and infiltration of immune cells, while macrophages have strong plasticity in acute and chronic inflammation.…”

“…It has also been shown that with the decline of renal function in patients with CKD, the body will continue to show low levels of inflammation in the absence of systemic or local obvious clinical manifestations of infection, mainly with the persistent increase of tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) as the signal [17]. Chronic inflammatory diseases not only have a persistent pro-inflammatory response but also have the possibility of an uncontrolled inflammatory response [18][19][20]. It has been found that almost all kidney diseases are accompanied by secretion of inflammatory factors and infiltration of immune cells, while macrophages have strong plasticity in acute and chronic inflammation.…”

Recent Progress on Polysaccharide-Based Hydrogels for Controlled Delivery of Therapeutic Biomolecules

“…When injected into the vocal fold of rabbits with laryngeal nerve denervation, an unprecedented recovery of vocal function was achieved. 62 …”

Injection laryngoplasty of human adipose-derived stem cell spheroids with hyaluronic acid-based hydrogel improves the morphological and functional characteristics of geriatric larynx

“…Regeneration of laryngeal tissues and restoration of intrinsic laryngeal functions are challenging problems that have yet to be addressed by existing injectable materials. Previously, with experience of injection laryngoplasty of diverse materials, including polycaprolactone, Pluronic F127, poly (lactic-co-glycolic acid) (PLGA), and adipose-derived extracellular matrix (ECM) [ 13 – 18 ], we have accumulated various experimental and analytical methods to assess the properties of injectable materials.…”