Injectable Materials for Vocal Cord Augmentation

Historical Context

• Paraffin - first used by Brunings in the early 20th century; abandoned due to granuloma formation
• Polytetrafluoroethylene (PTFE / Teflon) - reintroduced by Arnold in the 1960s; fell out of favor due to a rising frequency of granuloma formation and foreign body giant cell reactions, often requiring surgical excision with resulting tissue loss
• Absorbable gelatin sponge (Gelfoam) - introduced as a temporary measure; now largely supplanted by longer-lasting agents

Currently Used Injectable Materials

1. Autologous Fat

• Source: Harvested by liposuction from the abdomen or thigh; centrifuged and purified before injection
• Duration: Highly variable - results range from months to years; unpredictable resorption is the main limitation
• Properties: Viscoelastic studies show fat has nearly identical viscosity to true vocal fold mucosa and does not limit mucosal wave - the best rheological match of any injectable
• Injection: 18-gauge needle; typically requires overinjection by ~30% to compensate for expected resorption
• Considerations: Requires harvest (operating room), donor site morbidity is minor; not suitable for office-based injection; some studies show inconsistent results compared to type I thyroplasty for permanent paralysis
• Best for: Young patients, vocal fold atrophy, patients who may become candidates for permanent framework surgery later

2. Calcium Hydroxylapatite (CaHA)

• Composition: Microspheres of calcium hydroxylapatite (30%) suspended in an aqueous carboxymethylcellulose carrier gel (70%)
• Duration: ~1 to 2 years - the most durable of the current injectable options, and FDA-approved for laryngeal use
• Properties: The gel carrier is reabsorbed over weeks, leaving the CaHA microspheres which stimulate collagen formation; eventually the microspheres themselves are metabolized
• Injection: 25-27 gauge needle; over-inject by ~10% to account for gel reabsorption; placed lateral to the vocal ligament in the paraglottic space - superficial injection into Reinke's space must be avoided
• Considerations: Higher viscosity than vocal fold mucosa; patient-reported voice outcomes are somewhat poorer than hyaluronic acid but duration is longer; a rare foreign body reaction with giant cells has been documented; not ideal for lamina propria defects
• Best for: Unilateral paralysis expected to be permanent, or when a longer interval between injections is desired; presbylarynx

Calcium hydroxylapatite particle paste has been introduced as a durable injectable with effect around one year. - Scott-Brown's, p. 1149

3. Hyaluronic Acid (HA) Preparations

• Source: Cross-linked chains of hyaluronic acid (a natural polysaccharide found in the vocal fold lamina propria itself)
• Duration: Typically 4-6 months; some studies report up to 12 months
• Properties: Rheologically superior to most other injectables - best viscoelastic match to vocal fold mucosa among the non-autologous options; very low tissue reactivity; hydrophilic (absorbs water, can expand slightly post-injection)
• Injection: 25-27 gauge needle; suitable for both paraglottic and superficial intracordal injection
• Considerations: Low viscosity approximates vocal fold mucosa, making superficial injection relatively safe; rare granulomatous reaction reported; no risk of infectious transmission
• Best for: Office-based injection in awake patients; presbylarynx; short-term medialization while awaiting recovery; sulcus vocalis and soft tissue deficits

Viscoelastic properties best resemble the human vocal fold - Otorhinolaryngologist Review

4. Collagen-Based Products

a) Micronized Cadaveric Dermis - Cymetra (Alloderm regenerative tissue matrix)

• Source: Micronized alloderm (human cadaveric dermis); reconstituted with saline before use
• Duration: 3-9 months; radiographic evidence of material up to 11 months
• Properties: Minimal tissue response histologically; no serious allergic reactions in laryngoplasty reported
• Considerations: Theoretical risk of infectious transmission (human cadaveric tissue) - not documented clinically; requires over-injection; can cause small submucosal nodules if injected into Reinke's space
• Best for: Temporary medialization in patients with potential for RLN recovery; soft tissue deficits

b) Bovine Collagen - Zyderm I, Zyderm II, Zyplast

• Older preparations; shown effective for vocal fold paralysis, sulcus vocalis, and soft tissue defects
• Inflammatory changes (chronic inflammatory infiltrate with foreign body giant cells) observed histologically in some cases
• FDA approved for laryngeal injections
• Duration ~3 months
• Risk of allergic reaction to bovine protein; skin testing previously recommended

c) Engineered Human Collagen - Cosmoplast / Cosmoderm

• Laboratory-engineered purified human collagen; lower infection risk than cadaveric products
• Limited laryngeal track record compared to dermal filler use

5. Absorbable Gelatin Sponge (Gelfoam / Surgifoam)

• Composition: Bovine-derived gelatin powder mixed with saline to form a viscous paste
• Duration: 4-6 weeks - shortest duration of any current injectable
• Injection: 18-19 gauge needle required (high viscosity)
• Considerations: Historically important and very safe; minimal utility today because newer substances are easier to use and last longer; still useful for temporary augmentation when testing patient tolerance or when early recovery from RLN injury is expected
• Best for: Temporary measure; pre-planned short duration

6. Carboxymethylcellulose-Glycerine Gel

• Synthetic, biocompatible filler; used in some centers as a temporary injectable
• Duration: variable (weeks to months)
• Listed in Scott-Brown's among substances used for temporary glottic insufficiency relief

7. Autologous Fascia

• Source: Operatively harvested fascia (fascia lata, rectus sheath, temporal fascia)
• Duration: Up to 1 year
• Injection: 18-gauge needle into the vocalis muscle
• Considerations: Donor site morbidity not insignificant; minimal histologic tissue reaction; requires operative harvest; not suitable for office-based procedures

8. Polydimethylsiloxane (Bioplastique)

• A semi-permanent silicone microparticle suspension
• Provides longer-lasting augmentation but carries risk of migration and granuloma
• Not widely used due to adverse reaction profile; listed as a longer-lasting option in some older series

Comparison Summary

Clinical Considerations

• Medialization for paralysis: inject deep to the vocalis muscle in the paraglottic space - lateral to the vocal ligament
• Soft tissue deficits (atrophy, sulcus): inject intracordally, deep to the lamina propria, avoiding Reinke's space
• Superficial injections into Reinke's space cause stiffening, mucosal nodules, and poor phonatory outcomes that may require microsurgical correction

• Cummings Otolaryngology Head and Neck Surgery, Chapter on Vocal Fold Medialization by Injection
• Scott-Brown's Otorhinolaryngology Head & Neck Surgery, Chapter 78 (Paralysis of the Larynx), pp. 1149-1150
• Iowa Head and Neck Protocols - Injectable Substances for Injection Laryngoplasty
• Avdiyuk et al. (2025). In-Office Hyaluronic Acid Injection for Presbyphonia. J Clin Med, 14(3):960.