Controlled delivery of mesenchymal stem cells and growth factors using a nanofiber scaffold for tendon repair.
Controlled delivery of mesenchymal stem cells and growth factors using a nanofiber scaffold for tendon repair.
复制标题
使用纳米纤维支架进行肌腱修复的间质干细胞和生长因子的控制递送。
DOI：
10.1016/j.actbio.2013.02.008
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发表时间：
2013-06
影响因子：
9.7
通讯作者：
Thomopoulos, S.
中科院分区：
文献类型：
--
作者：
Manning, C. N.;Schwartz, A. G.;Liu, W.;Xie, J.;Havlioglu, N.;Sakiyama-Elbert, S. E.;Silva, M. J.;Xia, Y.;Gelberman, R. H.;Thomopoulos, S.
关键词：
肌腱修复后的结果往往是不令人满意的，尽管在手术技术和康复方法的改进。最近旨在增强修复的研究针对肌腱的少细胞性质以增强修复;然而，大多数用于递送生长因子和细胞的方法并不是针对致密结缔组织如肌腱而设计的。因此，我们开发了一种能够以手术可管理的形式提供生长因子和细胞的支架用于肌腱修复。将生长因子PDGF-BB沿着脂肪来源的间充质干细胞（ASC）并入基于肝素/纤维蛋白的递送系统（HBDS）中。然后将该水凝胶与静电纺丝的聚乳酸-共-乙醇酸（PLGA）骨架分层。HBDS允许以受控方式同时递送PDGF-BB和ASC，而PLGA骨架为手术处理和肌腱植入提供结构完整性。体外研究证实，细胞保持活力，并实现了持续的生长因子释放。在大型动物肌腱模型中的体内研究证实了该方法具有临床相关性，并且细胞在肌腱修复环境中保持活力。在解剖、组织学和mRNA水平上仅观察到轻微的免疫反应;术后9天在修复部位发现荧光标记的ASC和支架;在ASC处理的肌腱中观察到总DNA增加。这种新型的层状支架具有改善肌腱愈合的潜力，因为它能够以手术方便的方式同时递送细胞和生长因子。
Outcomes after tendon repair are often unsatisfactory, despite improvements in surgical techniques and rehabilitation methods. Recent studies aimed at enhancing repair have targeted the paucicellular nature of tendon for enhancing repair; however, most approaches for delivering growth factors and cells have not been designed for dense connective tissues such as tendon. Therefore, we developed a scaffold capable of delivering growth factors and cells in a surgically manageable form for tendon repair. The growth factor PDGF-BB along with adipose-derived mesenchymal stem cells (ASCs) was incorporated into a heparin/fibrin-based delivery system (HBDS). This hydrogel was then layered with an electrospun nanofiber poly-lactic-co-glycolic acid (PLGA) backbone. The HBDS allowed for the concurrent delivery of PDGF-BB and ASCs in a controlled manner, while the PLGA backbone provided structural integrity for surgical handling and tendon implantation. In vitro studies verified that the cells remained viable, and that sustained growth factor release was achieved. In vivo studies in a large animal tendon model verified that the approach was clinically relevant, and that the cells remained viable in the tendon repair environment. Only a mild immunoresponse was seen at dissection, histologically, and at the mRNA level; fluorescently-labeled ASCs and the scaffold were found at the repair site 9 days postoperatively; and increased total DNA was observed in ASC-treated tendons. The novel layered scaffold has the potential for improving tendon healing due to its ability to deliver both cells and growth factors simultaneously in a surgically convenient manner.
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影响因子：
1.9
作者：
GELBERMAN, RH;AMIEL, D;HARWOOD, F
通讯作者：
HARWOOD, F
影响因子：
4.8
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Gulotta, Lawrence V.;Kovacevic, David;Rodeo, Scott A.
通讯作者：
Rodeo, Scott A.
影响因子：
1.9
作者：
GELBERMAN, RH;STEINBERG, D;AKESON, W
通讯作者：
AKESON, W
影响因子：
2.8
作者：
Awad, HA;Boivin, GP;Butler, DL
通讯作者：
Butler, DL
影响因子：
10.8
作者：
Katta, P;Alessandro, M;Chase, GG
通讯作者：
Chase, GG