Recurrent laryngeal nerve regeneration using a self‐assembling peptide hydrogel

Abstract

Objectives/Hypothesis To regenerate defected recurrent laryngeal nerves (RLNs), various methods have been developed. However, no consistently effective treatments are currently available because of their insufficient functional recovery. RADA16‐I, a self‐assembling peptide used clinically as a hemostat, reportedly supports neurite outgrowth and functional synapse formation in vitro. The purpose of this study was to investigate the effect of RADA16‐I hydrogels on transected RLNs in rats. Study Design Animal experiments with controls. Methods Fifteen adult rats were divided into the following three groups: RADA16‐I (+), RADA16‐I (−), and neurectomy. A 6‐mm gap of the left RLN was bridged using an 8‐mm silicone tube in the RADA16‐I (−) and RADA16‐I (+) groups. Subsequently, RADA16‐I hydrogel was injected into the tube in the RADA16‐I (+) group. The surgical incisions were closed without any further treatment in the neurectomy group. After 8 weeks, laryngoscopy and electrophysiological and histological examinations were performed to evaluate the effect of RADA16‐I on nerve regeneration and thyroarytenoid muscle atrophy. Results Although most rats in the three groups exhibited no improvements of their vocal fold movement, partial recovery was observed in one rat in the RADA16‐I (+) group. The neurofilament‐positive areas and the number of myelinated nerves in the RADA16‐I (+) group were significantly higher than in the RADA16‐I (−) group. The area of the left thyroarytenoid muscle in the RADA16‐I (+) group was significantly larger than that of the neurectomy group. Conclusions Our results suggested that RADA16‐I hydrogel was effective for RLN regeneration. Level of Evidence NA Laryngoscope, 130:2420–2427, 2020

Functional recurrent laryngeal nerve regeneration using a silicon tube containing a collagen gel in a rat model

“…In a previous study, which analyzed the regeneration of severed recurrent laryngeal nerves with gaps between the stumps in rats, the use of a self-assembling peptide led to restoration of vocal fold movements in 1 of 5 rats [ 15 ]. However, in most studies, vocal fold movements were not restored despite nerve fiber connections [ 10 – 12 ].…”

“…Several previous studies have attempted to regenerate the transected recurrent laryngeal nerves using nerve guidance conduits primarily in animals such as rats. The results of several experiments performed using different tube materials, fillings, growth factors, and cells, have introduced varied types of conduits [9][10][11][12][13][14][15]. However, these studies were performed in different gap lengths between the recurrent laryngeal nerve stumps, and no study has examined the differences in outcomes with differing gap lengths.…”

Repair of Peripheral Nerve Injury Using Hydrogels Based on Self-Assembled Peptides

“…As suggested in Figure 3D, self-assembled polypeptides are not immunogenic. Therefore, developing SAPs that present immunogenic antigens has reasonable application prospects [66]. Long, unbranched nanofibers are formed in peptide self-assembly system and can effectively wrap the antigenic epitopes of pre-immunogenic drugs, reduce the level of immunity required by the body while simultaneously reducing the adjuvant effect [67].…”

Self-Assembling Peptides: From Design to Biomedical Applications

“…Furthermore, when assembled, SAPs can be used as scaffolds for cell and tissue regeneration [ 18 ] and carriers for drug delivery with controlled release, a low ratio of drug loss, a high stability and selectivity, and poor side effects [ 17 , 19 , 20 ].…”