Biomolecule gradient in micropatterned nanofibrous scaffold for spatiotemporal release.
Biomolecule gradient in micropatterned nanofibrous scaffold for spatiotemporal release.
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DOI：
10.1021/la302386u
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发表时间：
2012-09-25
期刊：
影响因子：
--
通讯作者：
Tan W
中科院分区：
文献类型：
--
作者：
Bonani W;Motta A;Migliaresi C;Tan W
支架的可控分子释放可以显著提高支架在体内外引导组织再生的能力。再生的关键是对多个分子（小基因、肽或较大蛋白质）的释放方向和动力学的精确调节。为此，我们通过编程沉积聚（ε-己内酯）（PCL）和聚（D，L-丙交酯-共-乙交酯）酸（PLGA）的异质纳米纤维，开发了电纺纳米纤维沿着支架厚度的梯度微图案。含有荧光团浸渍的纳米纤维的支架的共聚焦图像显示了实际和设计的梯度纤维图案的紧密匹配;热分析进一步显示了它们在组成上的匹配。使用酸封端的PLGA（PLGAac）和酯封端的PLGA（PLGAes）来降解PCL-PLGA支架中的分子，我们首次证明了它们在降解过程中的降解和分子量变化的差异。PLGAac纳米纤维在降解过程中随着纤维直径的逐渐和稳定的增加而更加稳定，导致PCL-PLGA支架的空间受限的分子递送。因此，PCL-PLGAac纳米纤维的图案用于设计通用的受控递送支架。为了检验梯度图案化PCL-PLGAac支架中的分子浸渍的PLGAac可以编程各种形式的分子释放的假设，模型分子，包括小荧光团和较大的蛋白质，分别用于延时释放研究。将顺式模式用作支架中的构建块，以编程将一种或多种蛋白质同时释放到支架的一侧或分别释放到支架的相对侧长达50天。结果表明，在200 μm的厚度范围内，蛋白质和小分子的分离效率分别达到88%和82%以上。除了通用的空间控制递送之外，微图案被设计成程序化蛋白质的顺序释放。本文提出的分层结构材料可以开发具有用于组织再生的定义的3D动态微环境的新型多功能支架。
Controlled molecule release from scaffolds can dramatically increase the scaffold ability of directing tissue regeneration in vitro and in vivo. Crucial to the regeneration is precise regulation over release direction and kinetics of multiple molecules (small genes, peptides, or larger proteins). To this end, we developed gradient micropatterns of electrospun nanofibers along the scaffold thickness through programming the deposition of heterogeneous nanofibers of poly(ε-caprolactone) (PCL) and poly(D,L-lactide-co-glycolide) acid (PLGA). Confocal images of the scaffolds containing fluorophore-impregnated nanofibers demonstrated close matching of actual and designed gradient fiber patterns; thermal analyses further showed their matching in the composition. Using acid-terminated PLGA (PLGAac) and ester-terminated PLGA (PLGAes) to impregnate molecules in the PCL-PLGA scaffolds, we demonstrated for the first time their differences in nanofiber degeneration and molecular weight change during degradation. PLGAac nanofibers were more stable with gradual and steady increase in the fiber diameter during degradation, resulting in more spatially confined molecule delivery from PCL-PLGA scaffolds. Thus, patterns of PCL-PLGAac nanofibers were used to design versatile controlled delivery scaffolds. To test the hypothesis that molecule-impregnated PLGAac in the gradient-patterned PCL-PLGAac scaffolds can program various modalities of molecule release, model molecules, including small fluorophores and larger proteins, were respectively used for time-lapse release studies. Gradient-patterns were used as building blocks in the scaffolds to program simultaneous release of one or multiple proteins to one side or, respectively, to the opposite sides of scaffolds for up to 50 days. Results showed that the separation efficiency of molecule delivery from all the scaffolds with a thickness of 200 μm achieved >88% for proteins and >82% for small molecules. In addition to versatile spatially controlled delivery, micropatterns were designed to program sequential release of proteins. The hierarchically structured materials presented here may enable development of novel multifunctional scaffolds with defined 3D dynamic microenvironments for tissue regeneration.
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影响因子：
4.9
作者：
Gandhi M;Srikar R;Yarin AL;Megaridis CM;Gemeinhart RA
通讯作者：
Gemeinhart RA
影响因子：
2
作者：
Moffat, Kristen L.;Wang, I-Ning Elaine;Rodeo, Scott A.;Lu, Helen H.
通讯作者：
Lu, Helen H.
影响因子：
3
作者：
Bailey, NA;Sandor, M;Mathiowitz, E
通讯作者：
Mathiowitz, E
影响因子：
14
作者：
Ionescu, Lara C.;Lee, Gregory C.;Sennett, Brian J.;Burdick, Jason A.;Mauck, Robert L.
通讯作者：
Mauck, Robert L.
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW