Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: NA Laryngoscope, 2024.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: NA Laryngoscope, 2024.
摘要：
目的：喉癌切除通常需要切除喉部，同时杀死同侧喉返神经（RLN）。在这种情况下,没有可靠恢复喉功能的重建方案，使患者具有严重的功能损害。为了解决这种未满足的临床需求，我们扩展了对三植入物粘膜的评估，肌肉，软骨重建方法旨在促进同侧RLN横切的猪半喉切除术模型中的功能性喉恢复。
方法：六头尤卡坦小型猪接受全层半喉癌切除和RLN横切术，然后使用合成的胶原聚合物粘膜进行透壁重建，肌肉，和软骨置换。为了确定添加治疗细胞群的效果，动物亚群接受含有表达运动终板的肌肉祖细胞（MEE）的胶原蛋白肌肉植入物和/或含有脂肪干细胞（ASC）衍生的软骨细胞样细胞的胶原蛋白软骨植入物。声学发声和喉肌电图（L-EMG）提供了功能评估，并使用免疫染色进行组织病理学分析来表征组织反应。
结果：六只动物中有五只在体重增加的术后4周存活，气道维护,和声音。不需要气管造口术或饲管。对所有动物的总体和组织学评估显示，气道粘膜上皮的植入物整合和再生重塑，肌肉，和软骨在没有材料介导的异物反应或生物降解的情况下。早期语音和L-EMG数据提示积极的功能结果。
结论：用胶原聚合物粘膜重建喉，肌肉，和软骨置换可以在半喉切除术和RLN横切后有效恢复功能。未来的临床前研究应该关注长期的功能结果。
方法：NA喉镜，2024.
方法：六头尤卡坦小型猪接受全层半喉癌切除和RLN横切术，然后使用合成的胶原聚合物粘膜进行透壁重建，肌肉，和软骨置换。为了确定添加治疗细胞群的效果，动物亚群接受含有表达运动终板的肌肉祖细胞（MEE）的胶原蛋白肌肉植入物和/或含有脂肪干细胞（ASC）衍生的软骨细胞样细胞的胶原蛋白软骨植入物。声学发声和喉肌电图（L-EMG）提供了功能评估，并使用免疫染色进行组织病理学分析来表征组织反应。
结果：六只动物中有五只在体重增加的术后4周存活，气道维护,和声音。不需要气管造口术或饲管。对所有动物的总体和组织学评估显示，气道粘膜上皮的植入物整合和再生重塑，肌肉，和软骨在没有材料介导的异物反应或生物降解的情况下。早期语音和L-EMG数据提示积极的功能结果。
结论：用胶原聚合物粘膜重建喉，肌肉，和软骨置换可以在半喉切除术和RLN横切后有效恢复功能。未来的临床前研究应该关注长期的功能结果。
方法：NA喉镜，2024.
