Engineering vascularized tissues remains a promising approach for treating ischemic cardiovascular diseases. The availability of 3D-bioprinted vascular grafts that induce therapeutic angiogenesis can help avoid necrosis and excision of ischemic tissues. Here, using a combination of living cells and biodegradable hydrogels, we fabricated 3D-printed biocompatible proangiogenic patches from endothelial cell-laden photo-crosslinked gelatin (EC-PCG) bioink and smooth muscle cell-encapsulated polyurethane (SMC-PU) bioink. Implantation of 3D-bioprinted proangiogenic patches in a mouse model showed that EC-PCG served as an angiogenic capillary bed, whereas patterned SMC-PU increased the density of microvessels. Moreover, the assembled patterns between EC-PCG and SMC-PU induced the geometrically guided generation of microvessels with blood perfusion. In a rodent model of hindlimb ischemia, the vascular patches rescued blood flow to distal tissues, prevented toe/foot necrosis, promoted muscle remodeling, and increased the capillary density, thereby improving the heat-escape behavior of ischemic animals. Thus, our 3D-printed vascular cell-laden bioinks constitute efficient and scalable biomaterials that facilitate the engineering of vascular patches capable of directing therapeutic angiogenesis for treating ischemic vascular diseases.

中文翻译：

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3D 打印的光交联明胶和聚氨酯水凝胶促血管生成贴片，其中载有血管细胞，用于治疗血管缺血性疾病


工程血管化组织仍然是治疗缺血性心血管疾病的有前途的方法。诱导治疗性血管生成的 3D 生物打印血管移植物的出现有助于避免缺血组织的坏死和切除。在这里，我们结合使用活细胞和可生物降解的水凝胶，利用充满内皮细胞的光交联明胶 (EC-PCG) 生物墨水和平滑肌细胞封装的聚氨酯 (SMC-PU) 生物墨水制造了 3D 打印的生物相容性促血管生成贴片。在小鼠模型中植入 3D 生物打印的促血管生成贴片表明，EC-PCG 作为血管生成毛细血管床，而图案化 SMC-PU 则增加了微血管的密度。此外，EC-PCG 和 SMC-PU 之间的组装模式诱导了具有血液灌注的微血管的几何引导生成。在后肢缺血的啮齿动物模型中，血管补片挽救了远端组织的血液流动，防止脚趾/足部坏死，促进肌肉重塑，并增加毛细血管密度，从而改善缺血动物的热逃逸行为。因此，我们的3D打印的充满血管细胞的生物墨水构成了高效且可扩展的生物材料，有助于血管补片的工程设计，能够指导治疗性血管生成以治疗缺血性血管疾病。