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载有地塞米松的双层 3D 管状支架减少气管置换吻合口处的再狭窄:体外和体内评估。

Dexamethasone loaded bilayered 3D tubular scaffold reduces restenosis at the anastomotic site of tracheal replacement: in vitro and in vivo assessments.

机构信息

Department of Nature-Inspired Nanoconvergence Systems, Korea Institute of Machinery and Materials, 156 Gajeongbuk-ro, Yuseong-gu, Daejeon 34103, Republic of Korea.

Department of Otorhinolaryngology-Head and Neck Surgery, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.

出版信息

Nanoscale. 2020 Feb 27;12(8):4846-4858. doi: 10.1039/c9nr10341d.

DOI:10.1039/c9nr10341d
PMID:32016227
Abstract

Despite recent developments in the tracheal tissue engineering field, the creation of a patient specific substitute possessing both appropriate mechanical and biointerfacial properties remains challenging. Most tracheal replacement therapies fail due to restenosis at the anastomosis site. In this study, we designed a robust, biodegradable, 3D tubular scaffold by combining electrospinning (ELSP) and 3D (three-dimensional) printing techniques for use in transplantation therapy. After that, we loaded dexamethasone (DEX) onto the 3D tubular scaffold using mild surface modification reactions by using polydopamine (PDA), polyethyleneimine (PEI), and carboxymethyl-β-cyclodextrin (βCD). As a result, the fabricated 3D tubular scaffold had robust mechanical properties and the chemical modifications were confirmed to have proceeded successfully by physico-chemical analysis. The surface treatments allowed for a larger amount of DEX to be loaded onto the βCD modified scaffold as compared to the bare group. In vitro and in vivo studies demonstrated that the DEX loaded 3D tubular scaffold exhibited significantly enhanced anti-inflammation activity, enhanced tracheal mucosal regeneration, and formation of a patent airway. From our results, we believe that our system may represent an innovative paradigm in tracheal tissue engineering by providing proper mechanical properties and successful formation of tracheal tissue as a means of remodeling and healing tracheal defects for use in transplantation therapy.

摘要

尽管气管组织工程领域最近取得了一些进展,但要创建具有适当机械和生物界面特性的患者特异性替代物仍然具有挑战性。大多数气管替代疗法由于吻合口再狭窄而失败。在这项研究中,我们通过结合静电纺丝(ELSP)和 3D(三维)打印技术设计了一种稳健、可生物降解的 3D 管状支架,用于移植治疗。之后,我们使用聚多巴胺(PDA)、聚乙烯亚胺(PEI)和羧甲基-β-环糊精(βCD)通过温和的表面改性反应将地塞米松(DEX)加载到 3D 管状支架上。结果表明,所制备的 3D 管状支架具有较强的机械性能,通过物理化学分析证实了化学修饰的成功进行。表面处理使 DEX 能够更多地负载到βCD 改性支架上,而不是裸组。体外和体内研究表明,负载 DEX 的 3D 管状支架表现出显著增强的抗炎活性、增强的气管黏膜再生以及通畅气道的形成。从我们的结果来看,我们相信我们的系统通过提供适当的机械性能和成功形成气管组织作为重塑和修复气管缺陷的手段,为气管组织工程提供了一种创新的范例,可用于移植治疗。

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