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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., (© 2023. The Author(s).)

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. [ABSTRACT FROM AUTHOR]

Introduction: Glottic insufficiency is characterized by an inability of the vocal fold to close completely during phonation leading to aspiration and phonation issues. Injectable biomaterials are preferred because it is easy, cheap and time-saving. However, current biomaterials used to augment the vocal fold have limitations such as inflammation and degradation. Therefore, better biomaterial with long term effects should be introduced. This study aims to optimize the best genipin-crosslinked gelatine hydrogel with the best physicomechanical properties for glottic insufficiency. Methods: Different percentages of gelatine and genipin ranging from 6% to 10% and 0.1% to 0.5% were fabricated. A total of 15 sets was tested with gelation time. After optimizing the gelation time, a total of 9 sets were further characterized using biodegradation, swelling ratio, crosslinking index, contact angle, porosity and water vapour transmission rate (WVTR). Results: With 6, 8, 10% of gelatine, 0.3% to 0.5% of genipin were able to achieve gelation time below 20 minutes at 37°C. For the biodegradation and swelling ratio test, 0.4% and 0.5% genipin of 6% and 8% gelatine exhibited less swelling and degradation. In addition, 6% and 8% gelatine with 0.5% genipin had higher crosslinking than 0.4% genipin. The optimized hydrogel sets had hydrophilic properties (<90°), 50 to 60% porosity and acceptable WVTR. Conclusion: The optimized 6% and 8% gelatine with 0.4% and 0.5% genipin had acceptable physicomechanical properties. Further characterization using pore size, biocompatibility and cellular response tests should be elucidated to strengthen the application of the gelatine hydrogel for vocal fold augmentation. [ABSTRACT FROM AUTHOR]