Department of Biomedical Engineering, Rowan University, Glassboro, NJ, USA.
Laboratory of Biomechanics, Riga Stradins University, Riga, Latvia.
J Tissue Eng. 2014 Nov 6;5:2041731414556561. doi: 10.1177/2041731414556561. eCollection 2014.
Effective cell invasion into thick electrospun biomimetic scaffolds is an unsolved problem. One possible strategy to biofabricate tissue constructs of desirable thickness and material properties without the need for cell invasion is to use thin (<2 µm) porous electrospun meshes and self-assembling (capable of tissue fusion) tissue spheroids as building blocks. Pre-stretched electrospun meshes remained taut in cell culture and were able to support tissue spheroids with minimal deformation. We hypothesize that elastic electrospun scaffolds could be used as temporal support templates for rapid self-assembly of cell spheroids into higher order tissue structures, such as engineered vascular tissue. The aim of this study was to investigate how the attachment of tissue spheroids to pre-stretched polyurethane scaffolds may interfere with the tissue fusion process. Tissue spheroids attached, spread, and fused after being placed on pre-stretched polyurethane electrospun matrices and formed tissue constructs. Efforts to eliminate hole defects with fibrogenic tissue growth factor-β resulted in the increased synthesis of collagen and periostin and a dramatic reduction in hole size and number. In control experiments, tissue spheroids fuse on a non-adhesive hydrogel and form continuous tissue constructs without holes. Our data demonstrate that tissue spheroids attached to thin stretched elastic electrospun scaffolds have an interrupted tissue fusion process. The resulting tissue-engineered construct phenotype is a direct outcome of the delicate balance of the competing physical forces operating during the tissue fusion process at the interface of the pre-stretched elastic scaffold and the attached tissue spheroids. We have shown that with appropriate treatments, this process can be modulated, and thus, a thin pre-stretched elastic polyurethane electrospun scaffold could serve as a supporting template for rapid biofabrication of thick tissue-engineered constructs without the need for cell invasion.
有效细胞侵入厚的静电纺仿生支架是一个未解决的问题。一种无需细胞侵入即可制造具有理想厚度和材料性能的组织构建体的可能策略是使用薄（<2 µm）多孔静电纺丝网和自组装（能够组织融合）组织球体作为构建块。预拉伸的静电纺丝网在细胞培养中保持紧绷，并能够最小变形地支撑组织球体。我们假设弹性静电纺丝支架可用作快速自组装细胞球体成更高阶组织结构（例如工程血管组织）的临时支撑模板。本研究的目的是研究组织球体附着在预拉伸聚氨酯支架上如何干扰组织融合过程。组织球体附着、扩散和融合后，被放置在预拉伸的聚氨酯静电纺丝基质上，并形成组织构建体。用纤维生成性组织生长因子-β消除孔缺陷的努力导致胶原蛋白和骨膜蛋白的合成增加，孔的大小和数量急剧减少。在对照实验中，组织球体在非粘附性水凝胶上融合并形成无孔的连续组织构建体。我们的数据表明，附着在薄拉伸弹性静电纺丝支架上的组织球体具有中断的组织融合过程。所得的组织工程构建体表型是在预拉伸弹性支架和附着的组织球体界面处组织融合过程中作用的竞争物理力之间的微妙平衡的直接结果。我们已经表明，通过适当的处理，可以调节这个过程，因此，薄的预拉伸弹性聚氨酯静电纺丝支架可以作为快速生物制造厚组织工程构建体的支撑模板，而无需细胞侵入。
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