Regeneration of Paralyzed Vocal Fold by the Injection of Plasmid DNA Complex-Loaded Hydrogel Bulking Agent,ACS Biomaterials Science & Engineering

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Regeneration of Paralyzed Vocal Fold by the Injection of Plasmid DNA Complex-Loaded Hydrogel Bulking Agent
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2019-01-22 00:00:00 , DOI: 10.1021/acsbiomaterials.8b01541
In Gul Kim ₁ , Mi Ri Park ₂ , Young Hwan Choi ₁ , Ji Suk Choi ₁ , Hee-Jin Ahn ₁ , Seong Keun Kwon ₁ , Jin Ho Lee ₂

Affiliation

Various growth factor delivery systems were used in the treatment of glottal insufficiency; however, relatively little attention has been paid to a gene delivery system for aspects of active vocal fold (VF) regeneration. Herein, we present a plasmid DNA (pDNA; bFGF gene encoding) complex-loaded alginate (ALG)/hyaluronic acid (HA) mixture hydrogel dispersed with polycaprolactone (PCL) microspheres that can enhance simultaneous regeneration of VF muscle and lamina propria, as well as have a bulking effect on atrophied VF. We have demonstrated long-term efficacy of bFGF synthesized from pDNA complex-transfected cells in vitro. PCL microspheres–dispersed ALG/HA hydrogel (with or without pDNA complex loading) are injected into rabbit VFs with recurrent laryngeal nerve denervation. The PCL microspheres dispersed in the hydrogel bulking agents remain stable at the applied site, leading to constant medialization of the paralyzed VF without significant initial volume loss even after 24 weeks. A regenerative effect for collagen deposition and HA synthesis around the injected site, which are major components of VF tissue, is well confirmed in the pDNA-complex-loaded hydrogel group. Moreover, the compensation of atrophied VFs also leads to the contact of bilateral VF and the remarkable recovery of voice function in the pDNA-complex-loaded group. Based on the results, pDNA (bFGF encoding) complex-loaded hydrogel dispersed with PCL microspheres may be employed as a bioactive bulking agent for the treatment of glottal insufficiency.

中文翻译：

注射质粒DNA配合物的水凝胶膨胀剂的注入使瘫痪的声带再生。

各种生长因子递送系统用于治疗声门关闭不全。然而，对于主动声带（VF）再生的方面，基因传递系统的关注相对较少。本文中，我们介绍了分散有聚己内酯（PCL）微球的质粒DNA（pDNA； bFGF基因编码）复合负载的藻酸盐（ALG）/透明质酸（HA）混合物水凝胶，它还可以增强VF肌肉和固有层的同时再生如对萎缩性室颤有膨大作用。我们已经证明了从pDNA复合体转染的细胞体外合成bFGF的长期疗效。将PCL微球分散的ALG / HA水凝胶（带或不带pDNA复合物）注射到兔VF中，并伴有喉返神经支配。分散在水凝胶填充剂中的PCL微球在应用部位保持稳定，即使在24周后，也能稳定地介导瘫痪的VF，而没有明显的初始体积损失。在pDNA复合物负载的水凝胶组中，已很好地证实了注射部位周围胶原沉积和HA合成的再生作用，这是VF组织的主要成分。此外，萎缩性室颤的补偿还导致双侧室颤的接触和pDNA复合物负荷组语音功能的显着恢复。根据结果，

更新日期：2019-01-22

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