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用于软组织工程的复合弹性体聚氨酯支架,其包含小肠黏膜下层。

Composite elastomeric polyurethane scaffolds incorporating small intestinal submucosa for soft tissue engineering.

作者信息

Da Lincui, Gong Mei, Chen Anjing, Zhang Yi, Huang Yizhou, Guo Zhijun, Li Shengfu, Li-Ling Jesse, Zhang Li, Xie Huiqi

机构信息

Laboratory of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.

Analytical & Testing Center, Research Center for Nano-biomaterials, Sichuan University, Chengdu 610065, China.

出版信息

Acta Biomater. 2017 Sep 1;59:45-57. doi: 10.1016/j.actbio.2017.05.041. Epub 2017 May 17.

DOI:10.1016/j.actbio.2017.05.041
PMID:28528117
Abstract

UNLABELLED

Although soft tissue replacement has been clinically successful in many cases, the corresponding procedure has many limitations including the lack of resilience and mechanical integrity, significant donor-site morbidity, volume loss with time, and fibrous capsular contracture. These disadvantages can be alleviated by utilizing bio-absorbable scaffolds with high resilience and large strain, which are capable of stimulating natural tissue regeneration. Hence, the chemically crosslinked tridimensional scaffolds obtained by incorporating water-based polyurethane (PU) (which was synthesized from polytetramethylene ether glycol, isophorone diisocyanate, and 2,2-bis(hydroxymethyl) butyric acid) into a bioactive extracellular matrix consisting of small intestinal submucosa (SIS) have been tested in this study to develop a new approach for soft tissue engineering. After characterizing the structure and properties of the produced PU/SIS composites, the strength, Young's modulus, and resilience of wet PU/SIS samples were compared with those of crosslinked PU. In addition, the fabricated specimens were investigated using human umbilical vein endothelial cells to evaluate their ability to enhance cell attachment and proliferation. As a result, the synthesized PU/SIS samples exhibited high resilience and were capable of enhancing cell viability with no evidence of cytotoxicity. Subcutaneous implantation in animals and the subsequent testing conducted after 2, 4, and 8weeks indicated that sound implant integration and vascularization occurred inside the PU/SIS composites, while the presence of SIS promoted cell infiltration, angiogenesis, and ultimately tissue regeneration. The obtained results revealed that the produced PU/SIS composites were characterized by high bioactivity and resilience, and, therefore, could be used for soft tissue engineering applications.

STATEMENT OF SIGNIFICANCE

Hybrid composites containing synthetic polymers with high mechanical strength and naturally derived components, which create a bio-mimetic environment, are one of the most promising biomaterials. Although synthetic polymer/ECM composites have been previously used for soft tissue repair, their resilience properties were not investigated in sufficient detail, while the development of elastic composites composed of synthetic polymers and ECMs in nontoxic aqueous solutions remains a rather challenging task. In this study, porous PU/SIS composites were fabricated in a non-toxic manner; the obtained materials exhibited sufficient mechanical support, which promote cell growth, angiogenesis, and tissue regeneration. The described method can be adapted for the development of scaffolds with various acellular matrices and subsequently used during the restoration of particular types of tissue.

摘要

未标注

尽管软组织置换在许多临床案例中取得了成功,但相应的手术存在诸多局限性,包括缺乏弹性和机械完整性、供体部位并发症严重、随时间体积缩小以及纤维包膜挛缩。利用具有高弹性和大应变的生物可吸收支架可以缓解这些缺点,这种支架能够刺激天然组织再生。因此,本研究测试了通过将水基聚氨酯(PU)(由聚四亚甲基醚二醇、异佛尔酮二异氰酸酯和2,2 - 双(羟甲基)丁酸合成)掺入由小肠黏膜下层(SIS)组成的生物活性细胞外基质中获得的化学交联三维支架,以开发一种软组织工程的新方法。在对制备的PU/SIS复合材料的结构和性能进行表征后,将湿PU/SIS样品的强度、杨氏模量和弹性与交联PU的进行了比较。此外,使用人脐静脉内皮细胞对制备的样本进行了研究,以评估它们增强细胞附着和增殖的能力。结果,合成的PU/SIS样品表现出高弹性,并且能够增强细胞活力,没有细胞毒性的迹象。在动物体内进行皮下植入,并在2、4和8周后进行后续测试,结果表明PU/SIS复合材料内部实现了良好的植入物整合和血管化,而SIS的存在促进了细胞浸润、血管生成,并最终促进了组织再生。获得的结果表明,制备的PU/SIS复合材料具有高生物活性和弹性,因此可用于软组织工程应用。

重要性声明

包含具有高机械强度的合成聚合物和天然衍生成分的混合复合材料,能够营造仿生环境,是最有前途的生物材料之一。尽管合成聚合物/细胞外基质复合材料此前已用于软组织修复,但其弹性性能并未得到充分详细的研究,而在无毒水溶液中由合成聚合物和细胞外基质组成的弹性复合材料的开发仍然是一项颇具挑战性的任务。在本研究中,以无毒方式制备了多孔PU/SIS复合材料;所获得的材料表现出足够的机械支撑,可促进细胞生长、血管生成和组织再生

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