Tissue-engineered trachea regeneration using decellularized trachea matrix treated with laser micropore technique
Tissue-engineered trachea regeneration using decellularized trachea matrix treated with laser micropore technique
复制标题
利用激光微孔技术处理的脱细胞气管基质进行组织工程气管再生
DOI：
10.1016/j.actbio.2017.05.010
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发表时间：
2017-08-01
影响因子：
9.7
通讯作者：
Zhou, Guangdong
中科院分区：
文献类型：
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作者：
Xu, Yong;Li, Dan;Zhou, Guangdong
组织工程化气管为长段气管缺损的修复提供了一种新的途径。然而，由于缺乏理想的生物降解支架，极大地限制了其临床应用。脱细胞气管基质（DTM）由于其天然的管状结构、软骨基质成分和生物可降解性而被认为是一种合适的气管软骨再生支架。然而，DTM的细胞残留和低孔隙率容易导致免疫原性和不完全的软骨再生。为了解决这些问题，在当前的研究中应用了激光切割技术（LMT）来改变气管样品的孔隙率，以促进脱细胞处理和细胞向内生长。脱细胞处理证明，与未处理的天然气管相比，LMT处理的样品中的细胞更容易去除。此外，在优化LMT和脱细胞处理方案后，LMT处理的DTM（LDTM）可以保持其原有的管状形状，只有轻微的细胞外基质损伤。在接种软骨细胞并体外培养8周后，细胞-LDTM构建体形成管状软骨，在微孔和两侧表面具有相对均匀的细胞分布。体内实验结果进一步证实，与天然气管相比，该构建体可以形成成熟的管状软骨，具有增加的DNA和软骨基质含量，以及增强的机械强度。这些结果表明，LDTM是一种理想的管状软骨再生支架材料，为气管软骨的功能性重建提供了一种很有前途的策略。意义缺乏理想的可降解支架材料极大地限制了组织工程气管的发展。脱细胞气管基质（DTM）被认为是气管软骨再生的理想支架材料。然而，DTM的细胞残留和低孔隙率容易导致免疫原性和不完全的软骨再生。通过激光脱细胞技术，本研究有效地提高了DTM的孔隙率和脱细胞效果。LMT处理后的DTM基本保持了原始的管状形状，有轻度的基质损伤。软骨细胞接种后，在体外培养和体内植入，构建体形成成熟的管状软骨的基质含量和机械强度类似于天然气管。本研究为气管软骨再生和功能重建提供了一种理想的支架材料和有希望的策略。(C)2017 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Tissue-engineered trachea provides a promising approach for reconstruction of long segmental tracheal defects. However, a lack of ideal biodegradable scaffolds greatly restricts its clinical translation. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration owing to natural tubular structure, cartilage matrix components, and biodegradability. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. To address these problems, a laser micropore technique (LMT) was applied in the current study to modify trachea sample porosity to facilitate decellular treatment and cell ingrowth. Decellularization processing demonstrated that cells in LMT treated samples were more easily removed compared with untreated native trachea. Furthermore, after optimizing the protocols of LMT and decellular treatments, the LMT treated DTM (LDTM) could retain their original tubular shape with only mild extracellular matrix damage. After seeding with chondrocytes and culture in vitro for 8 weeks, the cell-LDTM constructs formed tubular cartilage with relatively homogenous cell distribution in both micropores and bilateral surfaces. In vivo results further confirmed that the constructs could form mature tubular cartilage with increased DNA and cartilage matrix contents, as well as enhanced mechanical strength, compared with native trachea. Collectively, these results indicate that LDTM is an ideal scaffold for tubular cartilage regeneration and, thus, provides a promising strategy for functional reconstruction of trachea cartilage.Statement of SignificanceLacking ideal biodegradable scaffolds greatly restricts development of tissue-engineered trachea. Decellularized trachea matrix (DTM) is considered a proper scaffold for trachea cartilage regeneration. However, cell residual and low porosity of DTM easily result in immunogenicity and incomplete cartilage regeneration. By laser micropore technique (LMT), the current study efficiently enhanced the porosity and decellularized efficacy of DTM. The LMT-treated DTM basically retained the original tubular shape with mild matrix damage. After chondrocyte seeding followed by in vitro culture and in vivo implantation, the constructs formed mature tubular cartilage with matrix content and mechanical strength similar to native trachea. The current study provides an ideal scaffold and a promising strategy for cartilage regeneration and functional reconstruction of trachea. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.