Influence of hydrogel mechanical properties and mesh size on vocal fold fibroblast extracellular matrix production and phenotype

Abstract

Current clinical management of vocal fold (VF) scarring produces inconsistent and often suboptimal results. Researchers are investigating a number of alternative treatments for VF lamina propria (LP) scarring, including designer implant materials for functional LP regeneration. In the present study, we investigate the effects of the initial scaffold elastic modulus and mesh size on encapsulated VF fibroblast (VFF) extracellular matrix (ECM) production toward rational scaffold design. Polyethylene glycol diacrylate (PEGDA) hydrogels were selected for this study since their material properties, including mechanical properties, mesh size, degradation rate and bioactivity, can be tightly controlled and systematically modified. Porcine VFF were encapsulated in four PEGDA hydrogels with degradation half lives of ~25 days and initial elastic compressive moduli ranging from ~30 to 100 kPa and initial mesh sizes ranging from ~9 to 27 nm. After 30 days of static culture, VFF ECM production and phenotype in each formulation was assessed biochemically and histologically. Sulfated glycosaminoglycan synthesis increased in similar degree with both increasing initial modulus and decreasing initial mesh size. In contrast, elastin production decreased with increasing initial modulus but increased with decreasing initial mesh size. Both collagen deposition and the induction of a myofibroblastic phenotype depended strongly on initial mesh size but appeared largely unaffected by variations in initial modulus. The present results indicate that scaffold mesh size warrants further investigation as a critical regulator of VFF ECM synthesis. Furthermore, this study validates a systematic and controlled approach for analyzing VFF response to scaffold properties, which should aid in rational scaffold selection/design.

Hydrogel Microsphere Encapsulation of a Cell-Based Gene Therapy System Increases Cell Survival of Injected Cells, Transgene Expression, and Bone Volume in a Model of Heterotopic Ossification

“…20 The hydrogels in the current study were formed with 10% 10 kDa PEGDA, which has been estimated to have a mesh size of 280 Å . 21 Proteins having radii smaller than the hydrogel mesh size enjoy relatively free diffusion through the polymer. 22 Mature BMP-2 is a small protein (*16 kDa), and it has been suggested that it dimerizes immediately after synthesis.…”

3-D Non-UV Digital Printing of Hydrogel Microstructures by Optically Controlled Digital Electropolymerization

“…T ECHNIQUES that could precisely pattern hydrogels with tunable geometric shape and size in micro/nano scale are desired for developing hydrogels' applications in drug delivery [1], cell encapsulation [2], [3], cell-environment interaction research [4], [5] and tissue engineering [6]- [8]. To date, three-dimensional micro hydrogel structures have been created by a variety of methods, including photolithography, softlithography (e.g., micro-contact printing, microfluidic patterning, and micro molding) [9]- [11].…”

Long-Term Neurological and Behavioral Results of Biodegradable Scaffold Implantation in Mice Brain

“…Second, hydrogels are optimal in terms of mechanical compatibility with the brain and spinal cord tissue, Young's modulus values are in the range 1,700-2,000 Pa [34]. The compatibility of the mechanical characteristics is determining during the differentiation of progenitor cells [35] and influences overall success of implantation [36]. Third, hydrogels are promising drug compounds in the injury site [37].…”