Assessment of canine vocal fold function after injection of a new biomaterial designed to treat phonatory mucosal scarring.

OBJECTIVES: Most cases of irresolvable hoarseness are due to deficiencies in the pliability and volume of the superficial lamina propria of the phonatory mucosa. By using a US Food and Drug Administration-approved polymer, polyethylene glycol (PEG), we created a novel hydrogel (PEG30) and investigated its effects on multiple vocal fold structural and functional parameters. METHODS: We injected PEG30 unilaterally into 16 normal canine vocal folds with survival times of 1 to 4 months. High-speed videos of vocal fold vibration, induced by intratracheal airflow, and phonation threshold pressures were recorded at 4 time points per subject. Three-dimensional reconstruction analysis of 11.7 T magnetic resonance images and histologic analysis identified 3 cases wherein PEG30 injections were the most superficial, so as to maximally impact vibratory function. These cases were subjected to in-depth analyses. RESULTS: High-speed video analysis of the 3 selected cases showed minimal to no reduction in the maximum vibratory amplitudes of vocal folds injected with PEG30 compared to the non-injected, contralateral vocal fold. All PEG30-injected vocal folds displayed mucosal wave activity with low average phonation threshold pressures. No significant inflammation was observed on microlaryngoscopic examination. Magnetic resonance imaging and histologic analyses revealed time-dependent resorption of the PEG30 hydrogel by phagocytosis with minimal tissue reaction or fibrosis. CONCLUSIONS: The PEG30 hydrogel is a promising biocompatible candidate biomaterial to restore form and function to deficient phonatory mucosa, while not mechanically impeding residual endogenous superficial lamina propria.

Modulation of vocal fold scar fibroblasts by adipose-derived stem/stromal cells.

OBJECTIVES/HYPOTHESIS: To explore whether adipose-derived stem/stromal cells (ASCs) have therapeutic potential for treating scarred superficial lamina propria through the effects of secreted hepatocyte growth factor (HGF) on scar fibroblasts. STUDY DESIGN: In vitro study using coculture system. METHODS: Scar fibroblasts (SFs) were isolated from ferret vocal folds electrocauterized 2 weeks previously. ASCs were isolated from ferret lipoaspirated subcutaneous abdominal fat. For coculture experiments, the two cell types were combined in Transwell plates for 6 days, followed by 1 or 3 days of monoculture after removing the upper chamber. Assays were then performed on cells and media from the bottom chamber. We measured: 1) the production of hyaluronic acid (HA), collagen and HGF via enzyme-linked immunosorbent assays, 2) the expression of alpha-smooth muscle actin (alpha-SMA), 3) cell proliferation, and 4) apoptosis of SFs (2, 3, and 4 via flow cytometry). Other experiments examined the effects of HGF on SFs and the effects of HGF neutralization in the coculture system. RESULTS: Coculture led to significant decreases in SF collagen production (P < .05), cell proliferation (P < .05), and alpha-SMA expression (P < .05), whereas HA production increased (P < .05). Coculture also increased HGF secretion from ASCs (P < .05). Neutralization of HGF abolished the inhibitory effects of ASCs on SF collagen synthesis (P < .05). CONCLUSIONS: ASCs influence SFs to adopt a less fibrotic profile. It appears that HGF is at least one of the soluble factors responsible for this effect. Implanted ASCs could potentially ameliorate vocal fold scar by acting as long-term, intrinsic sources of HGF.

Implantable diagnostic device for cancer monitoring.

Biopsies provide required information to diagnose cancer but, because of their invasiveness, they are difficult to use for managing cancer therapy. The ability to repeatedly sample the local environment for tumor biomarker, chemotherapeutic agent, and tumor metabolite concentrations could improve early detection of metastasis and personalized therapy. Here we describe an implantable diagnostic device that senses the local in vivo environment. This device, which could be left behind during biopsy, uses a semi-permeable membrane to contain nanoparticle magnetic relaxation switches. A cell line secreting a model cancer biomarker produced ectopic tumors in mice. The transverse relaxation time (T(2)) of devices in tumor-bearing mice was 20+/-10% lower than devices in control mice after 1 day by magnetic resonance imaging (p<0.01). Short term applications for this device are numerous, including verification of successful tumor resection. This may represent the first continuous monitoring device for soluble cancer biomarkers in vivo.