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利用具有放射状微结构的无细胞圆柱状聚(丙交酯-共-乙交酯)支架在体内再生骨软骨缺损。

Regeneration of osteochondral defects in vivo by a cell-free cylindrical poly(lactide-co-glycolide) scaffold with a radially oriented microstructure.

机构信息

MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, China.

Division of Bioengineering, School of Chemical & Biomedical Engineering, Nanyang Technological University, Singapore, Singapore.

出版信息

J Tissue Eng Regen Med. 2018 Mar;12(3):e1647-e1661. doi: 10.1002/term.2592. Epub 2017 Nov 27.

Abstract

A scaffold with an oriented porous architecture to facilitate cell infiltration and bioactive interflow between neo-host tissues is of great importance for in situ inductive osteochondral regeneration. In this study, a poly(lactide-co-glycolide) (PLGA) scaffold with oriented pores in its radial direction was fabricated via unidirectional cooling of the PLGA solution in the radial direction, following with lyophilization. Micro-computed tomography evaluation and scanning electron microscopy observation confirmed the radially oriented microtubular pores in the scaffold. The scaffold had porosity larger than 90% and a compressive modulus of 4 MPa in a dry state. Culture of bone marrow stem cells in vitro revealed faster migration and regular distribution of cells in the poly(lactide-co-glycolide) scaffold with oriented pores compared with the random PLGA scaffold. The cell-free oriented macroporous PLGA scaffold was implanted into rabbit articular osteochondral defect in vivo for 12 weeks to evaluate its inductive tissue regeneration function. Histological analysis confirmed obvious tide mark formation and abundant chondrocytes distributed regularly with obvious lacunae in the cartilage layer. Safranin O-fast green staining showed an obvious boundary between the two layers with distinct staining results, indicating the simultaneous regeneration of the cartilage and subchondral bone layers, which is not the case for the random poly(lactide-co-glycolide) scaffold after the same implantation in vivo. The oriented macroporous PLGA scaffold is a promising material for the in situ inductive osteochondral regeneration without the necessity of preseeding cells.

摘要

具有定向多孔结构的支架有利于细胞浸润和新宿主组织之间的生物活性交换,对于原位诱导骨软骨再生非常重要。在这项研究中,通过聚(丙交酯-共-乙交酯)(PLGA)溶液在径向的单向冷却,随后进行冷冻干燥,制备了具有径向定向孔的 PLGA 支架。微计算机断层扫描评估和扫描电子显微镜观察证实了支架中具有径向定向的微管状孔。支架在干燥状态下具有大于 90%的孔隙率和 4 MPa 的压缩模量。体外骨髓干细胞培养表明,与随机 PLGA 支架相比,具有定向多孔的 PLGA 支架中细胞迁移更快且分布更规则。将无细胞的定向大孔 PLGA 支架植入兔关节骨软骨缺损中 12 周,以评估其诱导组织再生功能。组织学分析证实软骨层中有明显的潮标线形成,且大量软骨细胞分布规则,有空腔。番红 O-快绿染色显示两层之间有明显的边界,染色结果明显,表明软骨和软骨下骨层同时再生,而在相同的体内植入后,随机的 PLGA 支架则没有这种情况。定向大孔 PLGA 支架是一种很有前途的原位诱导骨软骨再生材料,无需预先接种细胞。

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