Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, U.S.A.
Laryngoscope. 2024 Nov;134(11):4604-4613. doi: 10.1002/lary.31616. Epub 2024 Jul 11.
Laryngeal cancer resections often require excision of portions of the larynx along with sacrifice of the ipsilateral recurrent laryngeal nerve (RLN). In such cases, there are no reconstructive options that reliably restore laryngeal function, rendering patients with severe functional impairment. To address this unmet clinical need, we extend our evaluation of a 3-implant mucosal, muscle, cartilage reconstruction approach aimed at promoting functional laryngeal restoration in a porcine hemilaryngectomy model with ipsilateral RLN transection.
Six Yucatan mini-pigs underwent full-thickness hemilaryngectomies with RLN transection followed by transmural reconstruction using fabricated collagen polymeric mucosal, muscle, and cartilage replacements. To determine the effect of adding therapeutic cell populations, subsets of animals received collagen muscle implants containing motor-endplate-expressing muscle progenitor cells (MEEs) and/or collagen cartilage implants containing adipose stem cell (ASC)-derived chondrocyte-like cells. Acoustic vocalization and laryngeal electromyography (L-EMG) provided functional assessments and histopathological analysis with immunostaining was used to characterize the tissue response.
Five of six animals survived the 4-week postoperative period with weight gain, airway maintenance, and audible phonation. No tracheostomy or feeding tube was required. Gross and histological assessments of all animals revealed implant integration and regenerative remodeling of airway mucosa epithelium, muscle, and cartilage in the absence of a material-mediated foreign body reaction or biodegradation. Early voice and L-EMG data were suggestive of positive functional outcomes.
Laryngeal reconstruction with collagen polymeric mucosa, muscle, and cartilage replacements may provide effective restoration of function after hemilaryngectomy with RLN transection. Future preclinical studies should focus on long-term functional outcomes.
NA Laryngoscope, 134:4604-4613, 2024.
喉癌切除术常需要切除部分喉，并牺牲同侧喉返神经（RLN）。在这种情况下，没有可靠的重建选择来恢复喉功能，导致患者严重功能受损。为了解决这一未满足的临床需求，我们扩展了对 3 种植入物黏膜、肌肉、软骨重建方法的评估，该方法旨在通过对猪半喉切除术模型中同侧 RLN 横断的研究，促进功能性喉重建。
6 只 Yucatan 小型猪接受全层半喉切除术，同时 RLN 横断，然后使用制造的胶原聚合物黏膜、肌肉和软骨替代物进行经壁重建。为了确定添加治疗性细胞群体的效果，部分动物接受了含有运动终板表达的肌肉祖细胞（MEE）的胶原肌肉植入物和/或含有脂肪干细胞（ASC）衍生的软骨细胞样细胞的胶原软骨植入物。声学发声和喉肌电图（L-EMG）提供了功能评估，免疫组织化学用于组织反应的特征描述。
6 只动物中有 5 只在术后 4 周内存活，体重增加，气道维持，可听见发声。不需要气管造口术或喂养管。所有动物的大体和组织学评估均显示，在没有材料介导的异物反应或生物降解的情况下，气道黏膜上皮、肌肉和软骨的植入物整合和再生重塑。早期的声音和 L-EMG 数据表明功能结果为阳性。
用胶原聚合物黏膜、肌肉和软骨替代物进行喉重建可能在 RLN 横断的半喉切除术后提供有效的功能恢复。未来的临床前研究应侧重于长期功能结果。
无 喉科学杂志，134：4604-4613，2024。
