3D bioprinting of proangiogenic constructs with induced immunomodulatory microenvironments through a dual cross-linking procedure using laponite incorporated bioink
3D bioprinting of proangiogenic constructs with induced immunomodulatory microenvironments through a dual cross-linking procedure using laponite incorporated bioink
复制标题
使用合成锂皂石的生物墨水通过双交联程序对具有诱导免疫调节微环境的促血管生成结构进行 3D 生物打印
DOI：
10.1016/j.compositesb.2021.109399
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发表时间：
2021-11-06
影响因子：
13.1
通讯作者：
Wang, Jinwu
中科院分区：
文献类型：
--
作者：
Ma, Zhenjiang;He, Hongtao;Wang, Jinwu
血管形成对于复杂的组织工程器官的生存和功能至关重要，而免疫微环境是有效血管形成的关键。3D生物打印是制造工程组织的一项强大技术。然而，通过3D生物打印重建具有免疫调节特性的功能化血管支架的报道很少。在这项研究中，我们通过同轴生物印迹方法将负载有干扰素-伽马的滑石粉加入到甲基丙烯酸明胶(GelMA)/海藻酸盐/四臂聚乙二醇丙烯酸酯(GAP)(GAP)的混合物中，得到了具有免疫调节特性的支架，这种连续的交联机制允许稳定地生产3D微纤维支架。磷灰石的加入优化了水凝胶的物理化学性能，改善了水凝胶的流变性和印刷可行性，同时提高了机械应力，使直接制备孔隙率增加、纤维直径减小的支架成为可能。此外，新的支架促进了趋化因子的表达，并加速了EPC向微纤维外围的迁移，形成了一层融合的内皮细胞。同时，该支架能够在早期释放干扰素-γ刺激巨噬细胞M1极化，随后随着钙钛矿的降解而通过释放Si4+、Mg2+诱导M2极化，成功地促进了新生血管的萌发和成熟，以及血管化的骨再生。我们的结果表明，GAP-干扰素-γ@Lap生物墨水与两步交联法相结合可以调节局部免疫微环境，帮助形成融合的内皮细胞，促进血管生成和组织再生，这可能为开发复杂的血管化组织提供一种有效而简单的策略。
Vascularization is vital for the survival and functionality of complex tissue-engineered organs, and immune microenvironment is pivotal for effective vascularization. 3D bioprinting is a powerful technique for manufacturing engineered tissues. However, the reconstruction of functionalized vascular scaffolds with immunomodulatory properties through 3D bioprinting has rarely been reported. In this study, we fabricated scaffolds with immunomodulatory properties by incorporating INF-gamma loaded laponite into the mixtures of gelatin methacrylate (GelMA)/alginate/4-arm poly(ethylene glycol) acrylate (PEG) (GAP) through coaxial bioprinting method with a sequential cross-linking mechanism that allows for stable production of 3D microfibrous scaffolds. Laponite addition optimized the hydrogel's physical and chemical performance, improved the rheological properties and printing feasibility while enhancing mechanical stress, making the direct fabrication of scaffolds with increased porosity and decreased filament diameter possible. Furthermore, new scaffolds facilitated the expression of chemotactic factors and accelerated EPC migration toward the microfiber peripheries to form a layer of confluent endothelium. Meanwhile, the scaffolds were capable of releasing IFN-gamma in the early stage to stimulate macrophage M1 polarization, followed by induction of M2 polarization via the release of Si4+, Mg2+ as the degradation of laponite occurred, which successfully improved the sprouting and mature of newly formed vasculature, as well as vascularized bone regeneration. Our results suggested that a combination of GAP-IFN gamma@Lap bioink with a dual-step cross-linking procedure could regulate the local immune microenvironment, aiding the formation of a confluent endothelium, promoting angiogenesis and tissue regeneration, which potentially provides an efficient and simple strategy for developing complex vascularized tissues.