An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering
An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering
复制标题
用于功能性肌腱组织工程的具有排列良好的纳米纤维的表观遗传生物活性复合支架
DOI：
10.1016/j.actbio.2017.09.036
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发表时间：
2018-01-15
影响因子：
9.7
通讯作者：
Ouyang, Hongwei
中科院分区：
文献类型：
--
作者：
Zhang, Can;Wang, Xianliu;Ouyang, Hongwei
由于缺乏理想的生物材料，肌腱修复往往是一个临床挑战。电纺丝排列纤维，类似于肌腱的超微结构，已被报道促进肌腱形成。然而，潜在的机制尚不清楚，排列的纤维本身不足以实现干细胞的肌腱分化。在此，基于我们观察到在排列纤维上培养的肌腱干/祖细胞（TSPCs）中他的张力去乙酰化酶（HDAC）的表达减少，我们提出了一种通过使用HDAC抑制剂小分子曲古抑素a （TSA）来增强排列纤维的肌腱生成作用的策略。采用稳定喷射静电纺丝法成功制备了负载TSA的聚l -乳酸（PLLA）排列纤维（a -TSA）支架，并证明了其持续释放TSA的能力。我们发现TSA结合PLLA排列纤维在指导肌腱分化中具有加性效应。此外，大鼠模型原位植入研究进一步证实了A-TSA支架促进了再生跟腱的结构和力学性能。本研究表明，HDAC参与了定向纤维结构的肌腱分化，HDAC与定向结构的结合可能是一种更有效的促进干细胞肌腱形成的策略。意义声明：电纺丝排列纤维，类似肌腱的超微结构，先前已报道可促进肌腱形成。然而，潜在的机制尚不清楚，排列的纤维本身不足以实现干细胞的肌腱分化。我们研究的独特之处在于，基于我们观察到在排列纤维上培养的肌腱干/祖细胞（TSPCs）中组蛋白去乙酰化酶（HDAC）的表达降低，我们提出了使用HDAC抑制剂小分子曲古抑素a （TSA）来增强排列纤维的肌腱生成作用的策略。采用稳定喷射静电纺丝法成功制备了负载TSA的聚l -乳酸（PLLA）排列纤维（a -TSA）支架，并证明了其持续释放TSA的能力。将具有生物活性的小分子TSA掺入并随后释放到静电纺丝排列纤维中，可以以一种可控的方式对体外和体内干细胞的肌腱生成进行生化和物理调节。总的来说，本研究提供了一个“将从细胞-材料相互作用中获得的生物学知识转化为优化生物材料（从biomat到biomat）”的模型。(C) 2017由Elsevier Ltd代表Acta Materialia Inc出版。
Poor tendon repair is often a clinical challenge due to the lack of ideal biomaterials. Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. Here, based on our observation of reduced expression of his tone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), an HDAC inhibitor. Such a TSA-laden poly (L-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. We found that TSA incorporated aligned fibers of PLLA had an additive effect in directing tenogenic differentiation. Moreover, the in situ implantation study in rat model further confirmed that A-TSA scaffold promoted the structural and mechanical properties of the regenerated Achilles tendon. This study demonstrated that HDAC was involved in the teno-differentiation with aligned fiber topography, and the combination of HDAC with aligned topography might be a more efficient strategy to promote tenogenesis of stem cells.Statement of SignificanceElectrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. The uniqueness of our studies are as follows, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), a HDAC inhibitor. Such a TSA-laden poly (L-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. The incorporation and subsequent release of bioactive small molecule TSA into electrospun aligned fibers allows a controllable manner for both biochemical and physical regulation of tenogenesis of stem cells both in vitro and in vivo. Collectively, the present study provides a model of "translating the biological knowledge learned from cell-material interaction into optimizing biomaterials (from Biomat-to-Biomat)". (C) 2017 Published by Elsevier Ltd on behalf of Acta Materialia Inc.