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聚(L-丙交酯-共-ε-己内酯)与无动物源胶原蛋白/透明质酸共混的微纤维支架,用于改善组织工程应用中的血管化。

Microfibrous scaffolds from poly(l-lactide-co-ε-caprolactone) blended with xeno-free collagen/hyaluronic acid for improvement of vascularization in tissue engineering applications.

机构信息

Experimental and Clinical Research Center, Diabetes and Obesity Research Laboratory, Kocaeli University, Turkey; Polymer Science and Technology Dept., Graduate School of Natural and Applied Sciences, Kocaeli University, Turkey; BIOMATEN, METU Center of Excellence in Biomaterials and Tissue Engineering, Ankara, Turkey.

Experimental and Clinical Research Center, Diabetes and Obesity Research Laboratory, Kocaeli University, Turkey; Department of Biology, Graduate School of Natural and Applied Sciences, Kocaeli University, Turkey.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Apr;97:31-44. doi: 10.1016/j.msec.2018.12.011. Epub 2018 Dec 6.

DOI:10.1016/j.msec.2018.12.011
PMID:30678916
Abstract

Success of 3D tissue substitutes in clinical applications depends on the presence of vascular networks in their structure. Accordingly, research in tissue engineering is focused on the stimulation of angiogenesis or generation of a vascular network in the scaffolds prior to implantation. A novel, xeno-free, collagen/hyaluronic acid-based poly(l-lactide-co-ε-caprolactone) (PLC/COL/HA) (20/9.5/0.5 w/w/w) microfibrous scaffold was produced by electrospinning. Collagen types I and III, and hyaluronic acid were isolated from human umbilical cords and blended with the GMP grade PLC. When compared with PLC scaffolds the PLC/COL/HA had higher water uptake capacity (103% vs 66%) which may have contributed to the decrease in its Young's Modulus (from 1.31 to 0.89 MPa). The PLC/COL/HA better supported adipose tissue-derived mesenchymal stem cell (AT MSC) adhesion; within 24 h the cell number on the PLC/COL/HA scaffolds was 3 fold higher. Co-culture of human umbilical vein endothelial cells and AT MSCs induced capillary formation on both scaffold types, but the PLC/COL/HA led to formation of interconnected vessels whose total length was 1.6 fold of the total vessel length on PLC. Clinical use of this scaffold would eliminate the immune response triggered by xenogeneic collagen and transmission of animal-borne diseases while promoting a better vascular network formation.

摘要

三维组织替代物在临床应用中的成功取决于其结构中血管网络的存在。因此,组织工程学的研究集中在支架植入前刺激血管生成或生成血管网络。通过静电纺丝制备了一种新型的无动物源、基于胶原/透明质酸的聚(L-丙交酯-co-ε-己内酯)(PLC/COL/HA)(20/9.5/0.5 w/w/w)微纤维支架。I 型和 III 型胶原以及透明质酸从人脐带中分离出来,并与 GMP 级 PLC 混合。与 PLC 支架相比,PLC/COL/HA 具有更高的吸水率(103%对 66%),这可能有助于降低其杨氏模量(从 1.31 到 0.89 MPa)。PLC/COL/HA 更有利于脂肪组织来源间充质干细胞(ATMSC)的黏附;24 小时内,PLC/COL/HA 支架上的细胞数量增加了 3 倍。人脐静脉内皮细胞和 ATMSC 的共培养诱导两种支架类型均形成毛细血管,但 PLC/COL/HA 导致形成相互连接的血管,其总长度是 PLC 上总血管长度的 1.6 倍。该支架的临床应用将消除异种胶原引发的免疫反应和动物源性疾病的传播,同时促进更好的血管网络形成。

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