Glottic insufficiency is one of the voice disorders affecting all demographics. Due to the incomplete closure of the vocal fold, there is a risk of aspiration and ineffective phonation. Current treatments for glottic insufficiency include nerve repair, reinnervation, implantation and injection laryngoplasty. Injection laryngoplasty is favored among these techniques due to its cost-effectiveness and efficiency. However, research into developing an effective injectable for the treatment of glottic insufficiency is currently lacking. Therefore, this study aims to develop an injectable gelatin (G) hydrogel crosslinked with either 1-ethyl-3-(3-dimethylaminpropyl)carbodiimide hydrochloride) (EDC) or genipin (gn). The gelation time, biodegradability and swelling ratio of hydrogels with varying concentrations of gelatin (6–10% G) and genipin (0.1–0.5% gn) were investigated. Some selected formulations were proceeded with rheology, pore size, chemical analysis and in vitro cellular activity of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs), to determine the safety application of the selected hydrogels, for future cell delivery prospect. 6G 0.4gn and 8G 0.4gn were the only hydrogel groups capable of achieving complete gelation within 20 min, exhibiting an elastic modulus between 2 and 10 kPa and a pore size between 100 and 400 μm. Moreover, these hydrogels were biodegradable and biocompatible with WJMSCs, as > 70% viability were observed after 7 days of in vitro culture. Our results suggested 6G 0.4gn and 8G 0.4gn hydrogels as potential cell encapsulation injectates. In light of these findings, future research should focus on characterizing their encapsulation efficiency and exploring the possibility of using these hydrogels as a drug delivery system for vocal fold treatment.

Objectives: Xerostomia is a prevalent sequelae among nasopharyngeal cancer (NPC) survivors; yet, effective treatment protocols have been elusive. This study was a prospective randomized clinical trial to compare the effects of saliva substitute mouthwash in nasopharyngeal cancer survivors with xerostomia, between two treatment arms, conducted in a tertiary center.Materials and methods: This study measured the effects within 4 weeks in relation to summated xerostomia inventory (SXI) and unstimulated whole saliva (UWS). Patients randomized into the interventional arm were prescribed an immunologically active saliva substitute (IASS), while patients in the control arm were prescribed a non-immunologically active mouthwash as placebo.Results: The study population consisted of 94 patients. There was a significant difference in SXI difference (p< 0.0001) and UWS difference (p< 0.0001) between control and interventional arms. No harmful side effects associated with the use of either mouthwash encountered throughout the study duration.Conclusion: IASS mouthwash significantly reduces subjective xerostomia scores measured using SXI and improves objective measurement of salivary flow using UWS among nasopharyngeal cancer survivors with xerostomia.Clinical relevance: IASS is significantly more effective in improving subjective and objective xerostomia measurements compared to non-immunologically active mouthwash. Additionally, this treatment is very safe, with superior side effect profiles.Trial registration: ClinicalTrials.govIdentifier: NCT04491435

Vocal fold injection is a preferred treatment in glottic insufficiency because it is relatively quick and cost-saving. However, researchers have yet to discover the ideal biomaterial with properties suitable for human vocal fold application. The current systematic review employing PRISMA guidelines summarizes and discusses the available evidence related to outcome measures used to characterize novel biomaterials in the development phase. The literature search of related articles published within January 2010 to March 2021 was conducted using Scopus, Web of Science (WoS), Google Scholar and PubMed databases. The search identified 6240 potentially relevant records, which were screened and appraised to include 15 relevant articles based on the inclusion and exclusion criteria. The current study highlights that the characterization methods were inconsistent throughout the different studies. While rheologic outcome measures (viscosity, elasticity and shear) were most widely utilized, there appear to be no target or reference values. Outcome measures such as cellular response and biodegradation should be prioritized as they could mitigate the clinical drawbacks of currently available biomaterials. The review suggests future studies to prioritize characterization of the viscoelasticity (to improve voice outcomes), inflammatory response (to reduce side effects) and biodegradation (to improve longevity) profiles of newly developed biomaterials.

Approaches to regenerate vocal fold in glottic insufficiency remains to be a focus for exploration. This is attributed to the applications of cells or biological molecules alone result in fast degradation and inadequate for regeneration. Development of an injectable hydrogel for glottic insufficiency is challenging, as it needs to be non-cytotoxic, elastic yet possess good strength and easy to fabricate. This gap prompts us to study the feasibility of our genipin(gn)-crosslinked gelatin (G) hydrogel in encapsulating Wharton’s Jelly Mesenchymal Stem Cells (WJMSCs) and basic fibroblast growth factor (bFGF) WJMSCs with the aim to provide regeneration in glottic insufficiency. WJMSCs was encapsulated into two optimised formulations with the density of 2,000,000 cells/mL. The encapsulated cells were tested for its morphology, cell viability, proliferation and migration. Then, the incorporation of basic fibroblast growth factor (bFGF) was done into a final formulation and was tested for the cellular response and in vitro inflammation. 6G 0.4gn demonstrated better cell viability after in vitro culturing for 7 day. After incorporation of bFGF into cell-laden 6G 0.4gn, encapsulated WJMSCs showed to have improved viability and migration. The inflammatory profile of the hydrogel was imperceptible and was regarded as minimal or no pro- and anti-inflammation. Altogether, we have first formulated 6G 0.4gn which is suitable to encapsulate WJMSCs and incorporation of bFGF. Current study fulfils the market need in vocal fold regeneration, by suggesting its rejuvenating potential in glottic insufficiency, yet this combined formulation should be studied further to justify its translation to clinical setting.

To study the effectiveness of early percutaneous transthyrohyoid injection laryngoplasty under local anesthesia in improving voice quality in unilateral vocal fold paralysis (UVFP) patients. Longitudinal data of 29 UVFP patients who underwent injection laryngoplasty within six months from the onset of the symptoms were studied. The injectate (0.5–1 mL) was hyaluronic acid-based material (Juvéderm ULTRA XC; Allergan Industrie, France) that was delivered under local anesthesia with transthyrohyoid approach using a double-bend 21G needle. Multidimensional voice outcomes employing: 1) Malay-Voice-Handicap Index-10 (mVHI-10); 2) maximum phonation time (MPT); and 3) acoustic analysis [jitter%, shimmer% and noise-harmonic ratio (NHR)] were used to assess the treatment progress. The voice parameters were measured at baseline (2 weeks pre-injection), and at the first and third months post-injection. The mean age of the 29 patients was 44.69 years, with a female-to-male ratio of 3.14:1. The voice outcomes measured at different time points were evaluated with repeated measures ANOVA. Significant improvement was observed from baseline to three months post injection laryngoplasty for mVHI-10, jitter, and NHR (p<0.001), shimmer (p=0.005) and MPT (p=0.018). Following the procedure, none of the patients developed any major complications. Office setting early transthyrohyoid injection laryngoplasty using a double-bend needle is a safe and effective procedure in patients with UVFP with evidence of significant improvement in voice and life quality.