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仿生胶原蛋白生物材料通过形成功能性肺泡诱导原位肺再生。

Biomimetic collagen biomaterial induces in situ lung regeneration by forming functional alveolar.

作者信息

Wang Linjie, Zhao Yannan, Yang Feng, Feng Meng, Zhao Yazhen, Chen Xi, Mi Junwei, Yao Yuanjiang, Guan Dongwei, Xiao Zhifeng, Chen Bing, Dai Jianwu

机构信息

Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Chongqing Engineering Research Center for Biomaterials and Regenerative Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China.

Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Chongqing Engineering Research Center for Biomaterials and Regenerative Medicine, Army Medical University (Third Military Medical University), Chongqing, 400038, China; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Biomaterials. 2020 Apr;236:119825. doi: 10.1016/j.biomaterials.2020.119825. Epub 2020 Jan 27.

Abstract

In situ restoration of severely damaged lung remains difficult due to its limited regeneration capacity after injury. Artificial lung scaffolds are emerging as potential substitutes, but it is still a challenge to reconstruct lung regeneration microenvironment in scaffold after lung resection injury. Here, a 3D biomimetic porous collagen scaffold with similar structure characteristics as lung is fabricated, and a novel collagen binding hepatocyte growth factor (CBD-HGF) is tethered on the collagen scaffold for maintaining the biomimetic function of HGF to improve the lung regeneration microenvironment. The biomimetic scaffold was implanted into the operative region of a rat partial lung resection model. The results revealed that vascular endothelial cells and endogenous alveolar stem cells entered the scaffold at the early stage of regeneration. At the later stage, inflammation and fibrosis were attenuated, the microvascular and functional alveolar-like structures were formed, and the general morphology of the injured lung was restored. Taken together, the functional 3D biomimetic collagen scaffold facilitates recovery of the injured lung, alveolar regeneration, and angiogenesis after acute lung injury. Particularly, this is the first study of lung regeneration in vivo guided by biomimetic collagen scaffold materials, which supports the concept that tissue engineering is an effective strategy for alveolar regeneration.

摘要

由于严重受损的肺在损伤后再生能力有限,其原位修复仍然困难。人工肺支架正成为潜在的替代物,但在肺切除损伤后在支架中重建肺再生微环境仍是一项挑战。在此,制备了一种具有与肺相似结构特征的三维仿生多孔胶原支架,并将一种新型的胶原结合肝细胞生长因子(CBD-HGF)连接在胶原支架上,以维持HGF的仿生功能,改善肺再生微环境。将该仿生支架植入大鼠部分肺切除模型的手术区域。结果显示,血管内皮细胞和内源性肺泡干细胞在再生早期进入支架。在后期,炎症和纤维化减轻,形成了微血管和功能性肺泡样结构,受损肺的总体形态得以恢复。综上所述,功能性三维仿生胶原支架有助于急性肺损伤后受损肺的恢复、肺泡再生和血管生成。特别是,这是首次在体内进行的由仿生胶原支架材料引导的肺再生研究,支持了组织工程是肺泡再生有效策略的概念。

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