MMP-sensitive PEG diacrylate hydrogels with spatial variations in matrix properties stimulate directional vascular sprout formation.
MMP-sensitive PEG diacrylate hydrogels with spatial variations in matrix properties stimulate directional vascular sprout formation.
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DOI：
10.1371/journal.pone.0058897
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Papavasiliou G
中科院分区：
文献类型：
--
作者：
Turturro MV;Christenson MC;Larson JC;Young DA;Brey EM;Papavasiliou G
固定化细胞外基质（ECM）信号的空间呈现和基质力学特性在定向和引导细胞行为和新生血管中起重要作用。这项工作的目的是探讨弹性模量梯度、固定化基质金属蛋白酶（MMP）敏感性和YRGDS细胞粘附配体是否能够指导组织工程支架中三维血管芽的形成。采用基于灌注的正面光聚合（PBFP）技术对PEGDA水凝胶进行了机械和生物功能梯度的工程设计。具有均匀机械性能、降解和固定化生物功能的大块光聚合水凝胶作为对照。梯度水凝胶的弹性模量降低80.4%，固定化YRGDS降低56.2%。PBFP水凝胶也表现出降解的梯度，在交联较多的区域降解时间为10-12小时，在交联较少的区域降解时间为4-6小时。我们建立了一个由内皮细胞和平滑肌细胞共培养聚集体组成的体外新生血管模型，用来评估这些梯度对血管芽形成的影响。在梯度水凝胶中，聚集体的入侵是双向的，在与梯度平行的方向上观察到萌芽排列，而在具有均匀性质的对照水凝胶中，聚集体的入侵是均匀的。在PBFP梯度水凝胶中，培养3周后发现，与梯度平行方向的聚集体芽长度是垂直方向的两倍。这种方向性在硬度增加、交联mmp敏感肽呈现和固定化YRGDS浓度的梯度区域更为突出。
The spatial presentation of immobilized extracellular matrix (ECM) cues and matrix mechanical properties play an important role in directed and guided cell behavior and neovascularization. The goal of this work was to explore whether gradients of elastic modulus, immobilized matrix metalloproteinase (MMP)-sensitivity, and YRGDS cell adhesion ligands are capable of directing 3D vascular sprout formation in tissue engineered scaffolds. PEGDA hydrogels were engineered with mechanical and biofunctional gradients using perfusion-based frontal photopolymerization (PBFP). Bulk photopolymerized hydrogels with uniform mechanical properties, degradation, and immobilized biofunctionality served as controls. Gradient hydrogels exhibited an 80.4% decrease in elastic modulus and a 56.2% decrease in immobilized YRGDS. PBFP hydrogels also demonstrated gradients in hydrogel degradation with degradation times ranging from 10–12 hours in the more crosslinked regions to 4–6 hours in less crosslinked regions. An in vitro model of neovascularization, composed of co-culture aggregates of endothelial and smooth muscle cells, was used to evaluate the effect of these gradients on vascular sprout formation. Aggregate invasion in gradient hydrogels occurred bi-directionally with sprout alignment observed in the direction parallel to the gradient while control hydrogels with homogeneous properties resulted in uniform invasion. In PBFP gradient hydrogels, aggregate sprout length was found to be twice as long in the direction parallel to the gradient as compared to the perpendicular direction after three weeks in culture. This directionality was found to be more prominent in gradient regions of increased stiffness, crosslinked MMP-sensitive peptide presentation, and immobilized YRGDS concentration.
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影响因子：
64.5
作者：
Choquet, D;Felsenfeld, DP;Sheetz, MP
通讯作者：
Sheetz, MP
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作者：
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