Development of a microporous annealed particle hydrogel for long‐term vocal fold augmentation

Abstract

Objectives/Hypothesis The purpose of this study was to develop and provide evidence of a novel permanent injectable biomaterial for vocal fold augmentation with the potential to treat glottic incompetence by evaluating its performance in two animal models. Study Design Animal model. Methods Microporous annealed particle (MAP) hydrogel was fabricated using a water‐in‐oil emulsion method and synthetically tuned to match the stiffness modulus of native vocalis muscle. Thirty‐two New Zealand White rabbits were administered unilateral injections of MAP (n = 16), saline (n = 8), and the clinical standard hyaluronic acid (Restylane‐L) (n = 8), and evaluated at day 0, and 6‐week, 4‐month, and 6‐month endpoints. Induced vocal fold vibration was recorded with a high‐speed camera prior to euthanization, with glottic closure and mucosal wave characteristics assessed both quantitatively and qualitatively by an experienced voice clinician. Histologic analysis was performed to assess scaffold permanence, immunogenicity, and vascularization within the scaffold. Results Histologic analysis confirmed the MAP gel treatment group maintained its volume without migration for 6 months postimplantation. Immune staining showed minimal to nonexistent immunogenicity over the course of the implant lifetime. Extensive tissue integration and vascularization was observed histologically within the MAP gel group by immunofluorescence staining. Mucosal wave was not impaired by any of the injected materials, including the MAP gel augmentation. Conclusions MAP gel is a nonresorbable biostimulatory injectable implant that provides superior tissue integration, stiffness matching, and permanence compared to current injectable implants, with retained biomechanical function, suggesting its potential as a new therapeutic for glottic incompetence. Level of Evidence NA Laryngoscope, 130:2432–2441, 2020

Nucleic Acid Delivery from Granular Hydrogels

“…The hydrogel precursor solution itself is technically injectable prior to crosslinking, but direct injection of the nanoparticle‐mixed precursor would not afford the microporous architecture needed to promote rapid cell infiltration and transfection. While we and other labs have previously reported on emulsion and microfluidic methods to generate granular scaffolds composed of micrometer‐sized spherical hydrogel particles, [ 18,58,59 ] the challenge has been loading charged nanoparticles within the precursor while avoiding aggregation and inactivation. Here, even though our enhanced HA‐coated DNA/PEI particle formulation was optimized for bulk gel loading, it did improve particle distribution within microfluidic generated particles as well (Figure S2c, Supporting Information).…”

In Vitro Evaluation of Biomaterials for Vocal Fold Injection: A Systematic Review

“…All of the studies were published between January 2010 and March 2021. In general, ten studies aimed to develop new formulation of biomaterials [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]; three studies focused in improving or characterizing current biomaterials [ 46 , 47 , 48 ]; one study investigated the effect of the biomaterials toward inflammation [ 49 ]; three studies intended to improve fabrication methods in order to produce better biomaterials [ 36 , 46 , 50 ]. The biomaterials studied in the included articles were carbomer hydrogel, micronized dermal graft tissue, crosslinked HA, HA with gelatine hydrogel, CaHA, carboxymethylcellulose (CMC), bovine collagen, micronized alloderm (Cymetra) (Lifecell Corp, Branchburg, NJ, USA), HA gel, carboxylic and hydroxylic multi-walled functionalized carbon, unequal particle sized middle viscosity and low viscosity HA, Rofilan (Laborata es Filorga, Lisbonne, Paris, France),Radiesse (Merz, Franksville, WI, USA),Restylane (Galderma Laboratories, Fort Worth, TX, USA), dextran beads in HA microsphere (MP), polyethylene glycol-diamine (PEG) microparticles, gelatine methacrylate MP, HA methacrylate, semi-IPN MP, glycol chitosan hydrogel, pluronic F127 with collagen, HA with poly(ethylene glycol) diacrylate (PEGDA) crosslinkers, silk protein based in HA suspension, resilin-like-polypeptide hydrogel, PEG30 hydrogel and polydimethylsiloxane (PDMS) with polydopamine (PDA).…”

Spatially heterogeneous epidermal growth factor release from microporous annealed particle (MAP) hydrogel for improved wound closure

“…Microgels were imaged at a 1 : 100 dilution in PBS and analyzed for particle diameter using a custom ImageXpress (Molecular Devices) module as previously described. 17 Microgels were imaged before and after lyophilization to confirm lyophilization did not alter physical properties.…”