Regeneration of human-ear-shaped cartilage with acellular cartilage matrix-based biomimetic scaffolds
Regeneration of human-ear-shaped cartilage with acellular cartilage matrix-based biomimetic scaffolds
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基于脱细胞软骨基质的仿生支架再生人耳形软骨
DOI：
10.1016/j.apmt.2020.100639
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发表时间：
2020-09-01
影响因子：
8.3
通讯作者：
Zhou, Guangdong
中科院分区：
文献类型：
--
作者：
Jia, Litao;Zhang, Ying;Zhou, Guangdong
组织工程技术为外耳再造提供了一条新的途径。虽然基于高分子支架的组织工程化耳廓再造技术已取得了首次临床突破，但由于支架残余物介导的无菌性炎症反应在不同患者间引发的临床疗效差异严重阻碍了其进一步的临床应用。因此，迫切需要一种合适的低炎症反应的天然支架来解决这个问题。在众多的天然材料中，脱细胞软骨基质（acellular cartilage matrix，ACM）被认为是理想的软骨特异性微环境仿生支架材料。然而，迄今为止，基于ACM的人耳软骨再生尚未取得突破性进展。目前的主要挑战是如何将ACM制备成具有精确人耳形状和适当机械强度的三维（3D）多孔支架。本研究以明胶为辅助交联剂，采用冷冻粉碎和脱细胞的方法制备ACM粉末，并将其制备成三维多孔支架。通过优化ACM和明胶的比例和浓度，使支架具有合适的孔结构和降解速率，并具有良好的机械强度和生物相容性。此外，将3D打印、聚己内酯（PCL）内核设计、浇铸成型和冷冻干燥技术相结合，可将ACM/明胶制成具有精确人耳形状和适当机械强度的多孔支架。最后，使用ACM/Gelatin-PCL支架和耳廓软骨细胞（弹性软骨），成功地再生了具有良好弹性和软骨特异性细胞外基质的人耳状软骨。这些结果为人耳软骨的应用和临床转化提供了重要依据。(c)2020爱思唯尔有限公司保留所有权利。
Tissue engineering technology provides a promising approach for external ear reconstruction. Although the first clinical breakthrough of tissue engineered auricular reconstruction has been achieved based on polymer scaffold, the discrepant clinical efficacy among different patients triggered by residual scaffold mediated aseptic inflammatory reaction seriously hinders its further clinical application. A proper natural scaffold with low inflammatory reaction is urgently required to address this problem. Among all the natural materials, acellular cartilage matrix (ACM) is considered to be the ideal cartilage-specific microenvironmental biomimetic scaffold. However, no breakthroughs have been achieved for the regeneration of human-ear-shaped cartilage based on ACM so far. The main challenge is how to prepare ACM into a threedimensional (3D) porous scaffold with precise human-ear shape and proper mechanical strength. In this study, ACM powder, prepared by freezing pulverization and decellularization, was successfully prepared into 3D porous scaffolds using gelatin as an auxiliary crosslinker. By optimizing proportion and concentration of ACM and gelatin, the scaffolds presented proper pore structure and degradation rate as well as good mechanical strength and biocompatibility. Furthermore, ACM/Gelatin could be fabricated into porous scaffolds with precise human-ear shape and proper mechanical strength by integrating 3D printing, polycaprolactone (PCL) inner core designing, cast molding, and freeze-drying technologies. Finally, human-ear-shaped cartilage with good elasticity and cartilage-specific extracellular matrices was successfully regenerated using the ACM/Gelatin-PCL scaffolds and auricular chondrocytes (elastic cartilage). All of these results provide important support for the application and clinical translation of human-ear-shaped cartilage. (c) 2020 Elsevier Ltd. All rights reserved.