Scarless Healing of Injured Vocal Folds Using an Injectable Hyaluronic Acid-Waterborne Polyurethane Hybrid Hydrogel to Tune Inflammation and Collagen Deposition

Abstract

Vocal fold (VF) scarring results from injury to the unique layered structure and is one of the main reasons for long-lasting dysphonia. A minimally invasive procedure with injectable hydrogels is a promising method for therapy. However, current surgical techniques or standard injectable fillers do not yield satisfactory outcomes. In this work, an injectable hybrid hydrogel consisting of oxide hyaluronic acid and hydrazide-modified waterborne polyurethane emulsion was injected precisely into the injury site and cross-linked in situ by a dynamic hydrazone bond. The prepared hydrogel displays excellent injectability and self-healing ability, showing favorable biocompatibility and biodegradability to facilitate endogenous newborn cell migration and growth for tissue regeneration. With the aim of evaluating the antifibrosis and regeneration capacity of the hybrid hydrogel in the VF scarring model, the morphology and vibration characteristics of VFs, inflammatory response, and healing status were collected. The hybrid hydrogel can decrease the inflammation and increase the ratio of collagen III/collagen I to heal damaged scar-free tissue. Fascinatingly, the mucosal wave oscillations of healing VF by injecting the hybrid hydrogel were vibrated like the normal VF, achieving functional restoration. This work highlights the utility of hybrid hydrogels consisting of synthetic biodegradable waterborne polyurethane emulsions and natural hyaluronic acid as promising biomaterials for scarless healing of damaged VFs.

Toward mechanically robust self-healing polyurethanes using dynamics chemistry

“…Larger bond energy can provide higher mechanical properties. Dynamic covalent bonds that have been used in self-healing PUs include the disulfide bond, [83][84][85] Diels-Alder bond, [86][87][88][89] borate ester bond, 84,[90][91][92] imine bond, 93,94 hydrazone bond [95][96][97] and urethane bond. 98…”

A tough, antibacterial and antioxidant hydrogel dressing accelerates wound healing and suppresses hypertrophic scar formation in infected wounds

“…Based on rabbit ear hypertrophic scar model, there are many meaningful researches reported in recent years. Guided by the idea of preventing of scar formation, the scar could be suppressed by various ways, such as inhibiting TGF-β or Engrailed-1 [ [18] , [19] , [20] ], reducing inflammatory reactions [ 21 ], and regulating vascular proliferation and collagen deposition [ 22 ]. Also, mechanical regulation or mediated iron death through microneedles has achieved promising results in the treatment of HSs [ 23 , 24 ].…”

A biodegradable injectable fluorescent polyurethane-oxidized dextran hydrogel for non-invasive monitoring

“…[39][40][41] Therefore, polyurethane-based hydrogels have been widely used in the biomedical field. [42][43][44][45][46][47] In this work, in order to achieve noninvasive monitoring of biodegradable hydrogels, we prepared an injectable fluorescent PU-OD hydrogel by dynamic cross-linking fluorescent PU emulsion with oxidized dextran (ODex), where the fluorescent PU emulsion was synthesized by using TPE-NH 2 as a chain extender and adipic dihydrazide (ADH) as an end-capping agent. The hydrogel can effectively be loaded with doxorubicin hydrochloride, and the drug release can be monitored by fluorescence changes.…”