Department of Orthopedic Surgery, Stanford University, 300 Pasteur Drive, Stanford, CA, 94305, USA.
Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.
Macromol Biosci. 2020 Oct;20(10):e2000204. doi: 10.1002/mabi.202000204. Epub 2020 Aug 13.
Numerous hydrogel-based culture systems are used to create in vitro model for prevascularization. Hydrogels used to induce a microenvironment conducive to microvessel formation are typically soft and fast degradable, but often suffer from maintaining a lasting perfusable channel in vitro. Here, a dual hydrogel system that consists of photo-crosslinkable gelatin methacrylate (GelMA) and polyethylene glycol dimethacrylate (PEGDMA) is reported. GelMA hydrogels present soft and rapidly degradable properties and show microporous structures while PEGDMA is relatively stiff, almost nondegradable in vitro, and less porous. The dual hydrogel system is sequentially photo-crosslinked to construct an endothelial cell (EC)-lined perfusable PEGDMA channel and surrounding GelMA for endothelial vascular networks. Such dual hydrogel system exhibits seamless integration of the stiff PEGDMA channel and the surrounding soft GelMA, and facilitates rapid EC sprouting and extensive microvessel formation from a stable endothelium on the PEGDMA channel into the GelMA. Furthermore, diffusivity of biomolecules in the perfusable dual hydrogel system is affected by both the structural and physicochemical properties of the hydrogel system and the microvascular networks formed in the system. The establishment of the dual hydrogel system for vascularization holds great promise as an in vitro angiogenesis model and prevascularization strategy of large tissue constructs.
有许多基于水凝胶的培养系统被用于创建体外血管化模型。用于诱导有利于微血管形成的微环境的水凝胶通常是柔软且快速降解的，但往往难以在体外维持持久的可灌注通道。在这里，报道了一种由光交联明胶甲基丙烯酰胺（GelMA）和聚乙二醇二甲基丙烯酰胺（PEGDMA）组成的双水凝胶系统。GelMA 水凝胶具有柔软和快速降解的特性，并呈现微孔结构，而 PEGDMA 相对较硬，几乎不可在体降解，且孔隙较少。该双水凝胶系统通过顺序光交联来构建内皮细胞（EC）衬里的可灌注 PEGDMA 通道和周围的 GelMA 以形成内皮血管网络。这种双水凝胶系统实现了刚性 PEGDMA 通道和周围柔软的 GelMA 的无缝集成，并促进了 EC 快速发芽以及从 PEGDMA 通道上稳定的内皮向 GelMA 中广泛形成微血管。此外，可灌注双水凝胶系统中的生物分子扩散性受到水凝胶系统的结构和物理化学性质以及系统中形成的微血管网络的影响。双水凝胶系统的建立为血管生成提供了一种有前途的体外血管生成模型和大组织构建的预血管化策略。
