Controlled release of hepatocyte growth factor from a bovine acellular scaffold for vocal fold reconstruction

Abstract

A bovine acellular scaffold was found to facilitate tissue remodeling in a rat model of vocal fold injury, whereas hepatocyte growth factor (HGF) has been shown to have an anti-scarring effect in the larynx. This study examined the loading and release kinetics of HGF in vitro, and the potential of the acellular scaffold as a timed-release system for the delivery of HGF in vivo. Bilateral wounds were created in the posterior vocal folds of 20 rats, with HGF-loaded acellular scaffolds implanted into the wounds unilaterally, and scaffolds without HGF implanted into the contralateral vocal folds as control. The rats were humanely sacrificed after 3, 7, 30, and 90 days and their larynges were examined histologically and immunohistochemically. Expressions of key matrix proteins in the vocal fold coronal sections were quantified by digital image analysis. Results demonstrated a gradual, sustained release of HGF for at least 7 days in vitro, consistent with the detection of glycosaminoglycans inherent of the scaffold. In rat vocal folds implanted with HGFloaded scaffolds, apparently fewer inflammatory cells were observed 3 days after surgery when compared to the control. The mean relative densities of collagen III and hyaluronic acid were significantly lower than those of the control 7 days after surgery. Scaffold implants were apparently degraded by 3 months in all animals, with no evidence of fibrosis or calcification. These data suggested that the bovine acellular scaffold could be promising for the exogenous delivery of select growth factors in vivo.

Hepatocyte Growth Factor-Loaded Biomaterials for Mesenchymal Stem Cell Recruitment

“…They came to similar release kinetics for HGF from acellular scaffolds. They showed a total release of 32.6% HGF after 7 days, which is in accordance with our results [33]. For both of our gels, the HGF release is well acceptable and will be analyzed further in terms of cell migration and degradation properties in our in vivo model.…”

Nonlinear viscoelastic characterization of human vocal fold tissues under large-amplitude oscillatory shear (LAOS)

“…Various types of biological materials and biomimetic scaffolds have been proposed as candidates of tissue substitutes for vocal fold reconstruction involving surgical repair of lamina propria deficits, including scarring, fibrosis, tissue loss and atrophy. Such materials have included biologic ECM scaffolds, HA hydrogels, as well as aligned biomimetic scaffolds being identified as promising implants for vocal fold repair [24-27]. A better characterization of their nonlinear viscoelastic properties under LAOS in comparison with those of the vocal fold cover and vocal ligament would allow for optimized functional biomechanical and vibratory performance of the tissue substitutes during phonation.…”

Regenerative Medicine of the Larynx. Where are we Today? A Review

“…Although HGF has been reported to increase HA production by hVFFs, they found that by day 7, the level of HA in the HGF-loaded group was statistically lower than that of the control. 47 Despite strong effects in experimental settings before, it seemed that the HGF-loaded scaffold showed a rather weak effect in the in vivo study. The same group recently published a work using the human umbilical vein as a scaffold.…”