<br>用于工程组织新血管化的细胞负载梯度水凝胶支架,Advanced Healthcare Materials

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用于工程组织新血管化的细胞负载梯度水凝胶支架
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2021-01-29 , DOI: 10.1002/adhm.202001706
Yusheng J He ₁ , Martin F Santana ₂ , Austeja Staneviciute ₂ , Marja B Pimentel ₂ , Feipeng Yang ₂ , Jacob Goes ₂ , Keigo Kawaji ₂ , Marcella K Vaicik ₂ , Rayan Abdulhadi ₂ , Narutoshi Hibino ₁ , Georgia Papavasiliou ₂

Affiliation

机械特性、物理结构和生化成分的梯度存在于各种复杂组织中，但能够研究这些细胞过程线索的 3D 体外模型，特别是那些有助于工程组织血管化的线索是有限的。据报道，采用光聚合方法来创建充满细胞的水凝胶生物材料，该生物材料具有解耦和组合的模量梯度、固定化细胞粘附肽（RGD）浓度和蛋白水解降解，从而能够空间封装血管球体，以阐明它们对 3D 培养中血管萌芽的影响。封装在这些梯度支架中的血管球体在总芽长度上表现出空间变化。呈现固定 RGD 梯度的支架促进偏向血管萌芽，以增加 RGD 浓度。重要的是，偏向发芽被发现依赖于固定的 RGD 梯度特征，包括幅度和斜率，这些因素的增加有助于显着增强偏向发芽响应。相反，在 RGD 和模量具有相反梯度的组合梯度支架中观察到偏向发芽反应的减少。本研究首次展示了使用充满细胞的生物材料平台来系统地研究多个支架梯度以及梯度斜率、大小和方向对 3D 培养中血管出芽反应的作用。

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Cell‐Laden Gradient Hydrogel Scaffolds for Neovascularization of Engineered Tissues

Gradients in mechanical properties, physical architecture and biochemical composition exist in a variety of complex tissues, yet 3D in vitro models that enable investigation of these cues on cellular processes, especially those contributing to vascularization of engineered tissues are limited. Here, a photopolymerization approach to create cell‐laden hydrogel biomaterials with decoupled and combined gradients in modulus, immobilized cell adhesive peptide (RGD) concentration, and proteolytic degradation enabling spatial encapsulation of vascular spheroids is reported to elucidate their impact on vascular sprouting in 3D culture. Vascular spheroids encapsulated in these gradient scaffolds exhibit spatial variations in total sprout length. Scaffolds presenting an immobilized RGD gradient promote biased vascular sprouting toward increasing RGD concentration. Importantly, biased sprouting is found to be dependent on immobilized RGD gradient characteristics, including magnitude and slope, with increases in these factors contributing to significant enhancements in biased sprouting responses. Conversely, reduction in biased sprouting responses is observed in combined gradient scaffolds possessing opposing gradients in RGD and modulus. The presented work is the first to demonstrate the use of a cell‐laden biomaterial platform to systematically investigate the role of multiple scaffold gradients as well as gradient slope, magnitude and orientation on vascular sprouting responses in 3D culture.

更新日期：2021-04-08

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