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Large animal in vivo evaluation of a binary blend polymer scaffold for skeletal tissue-engineering strategies; translational issues.
Journal of Tissue Engineering and Regenerative Medicine ( IF 3.1 ) Pub Date : 2015-02-18 , DOI: 10.1002/term.2007
James O Smith 1 , Edward R Tayton 1 , Ferdous Khan 2 , Alexander Aarvold 1 , Richard B Cook 3 , Allen Goodship 4 , Mark Bradley 2 , Richard O C Oreffo 1
Affiliation  

Binary blend polymers offer the opportunity to combine different desirable properties into a single scaffold, to enhance function within the field of tissue engineering. Previous in vitro and murine in vivo analysis identified a polymer blend of poly(l-lactic acid)-poly(ε-caprolactone) (PLLA:PCL 20:80) to have characteristics desirable for bone regeneration. Polymer scaffolds in combination with marrow-derived skeletal stem cells (SSCs) were implanted into mid-shaft ovine 3.5 cm tibial defects, and indices of bone regeneration were compared to groups implanted with scaffolds alone and with empty defects after 12 weeks, including micro-CT, mechanical testing and histological analysis. The critical nature of the defect was confirmed via all modalities. Both the scaffold and scaffold/SSC groups showed enhanced quantitative bone regeneration; however, this was only found to be significant in the scaffold/SSCs group (p = 0.04) and complete defect bridging was not achieved in any group. The mechanical strength was significantly less than that of contralateral control tibiae (p < 0.01) and would not be appropriate for full functional loading in a clinical setting. This study explored the hypothesis that cell therapy would enhance bone formation in a critical-sized defect compared to scaffold alone, using an external fixation construct, to bridge the scale-up gap between small animal studies and potential clinical translation. The model has proved a successful critical defect and analytical techniques have been found to be both valid and reproducible. Further work is required with both scaffold production techniques and cellular protocols in order to successfully scale-up this stem cell/binary blend polymer scaffold. © 2015 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

中文翻译:

用于骨骼组织工程策略的二元共混聚合物支架的大型动物体内评估;翻译问题。

二元共混聚合物提供了将不同所需特性组合到单个支架中的机会,以增强组织工程领域的功能。先前的体外和鼠体内分析确定了聚 (l-乳酸)-聚 (ε-己内酯) (PLLA:PCL 20:80) 的聚合物混合物具有骨再生所需的特性。将聚合物支架与骨髓来源的骨骼干细胞 (SSC) 联合植入中轴绵羊 3.5 cm 胫骨缺损中,并将骨再生指标与单独植入支架和 12 周后有空缺损的组进行比较,包括微CT、机械测试和组织学分析。通过所有方式确认了缺陷的严重性。支架组和支架/SSC 组均显示出增强的定量骨再生;然而,这仅在支架/SSC 组中发现显着(p = 0.04),并且在任何组中都没有实现完全的缺陷桥接。机械强度明显低于对侧对照胫骨(p < 0.01),不适合临床环境中的全功能负荷。本研究探讨了这样一个假设,即与单独使用支架相比,细胞疗法将增强临界尺寸缺陷中的骨形成,使用外部固定结构,以弥合小动物研究和潜在临床转化之间的扩大差距。该模型已被证明是一个成功的关键缺陷,并且已发现分析技术既有效又可重复。为了成功扩大这种干细胞/二元混合聚合物支架的规模,支架生产技术和细胞方案都需要进一步的工作。© 2015 作者。John Wiley & Sons, Ltd. 出版的《组织工程和再生医学杂志》。
更新日期:2019-11-01
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