Three-dimensional (3D) bioprinting holds the promise to fabricate tissue and organ substitutes for regenerative medicine. However, the lack of bioactive inks to fabricate and support functional living constructs is one of the main limitations hindering the progress of this technology. In this study, a biofunctional human-based nanocomposite bioink (HUink) composed of platelet lysate hydrogels reinforced by cellulose nanocrystals is reported. When combined with suspended bioprinting technologies, HUink allows the biofabrication of 3D freeform constructs with high resolution and integrity, mimicking the hierarchical nano-to-macro fibrillary composition of native tissues. Remarkably, HUink supports bioprinting of stem cells with high viability immediately after extrusion and over long-term cell culture without the need for additional biochemical or animal-derived media supplementation. As opposed to typical polymer-based bioinks, the pool of growth factors, cytokines and adhesion proteins in HUink boosts cell spreading and proliferation, stimulating the fast production of cell-secreted extracellular matrix. This innovative bioprinting platform with unpaired biofunctionality allows the fabrication of complex freeform cell-laden constructs that can ultimately be applied in the development of xeno-free 3D tissue models for in vitro research or to develop tissue and organ surrogates for clinical applications.

中文翻译：

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基于人类血小板裂解物的纳米复合生物墨水，用于生物印刷分层的原纤维结构。

三维（3D）生物打印技术有望制造再生医学的组织和器官替代品。然而，缺乏生物活性油墨来制造和支持功能性的生命构造是阻碍该技术发展的主要限制之一。在这项研究中，报道了由纤维素纳米晶体增强的血小板溶解产物水凝胶组成的生物功能性人类纳米复合生物墨水（HUink）。当与悬浮生物打印技术结合使用时，HUink可以高分辨率和完整性地生物制造3D自由形式的构建体，从而模仿天然组织的从纳米到宏观的原纤维组成。值得注意的是 HUink支持挤出后和长期的细胞培养后立即进行具有高生存力的干细胞生物打印，而无需额外的生化或动物来源的培养基补充。与典型的基于聚合物的生物墨水相反，HUink中的生长因子，细胞因子和粘附蛋白的集合可促进细胞扩散和增殖，从而刺激细胞分泌的细胞外基质的快速产生。这种具有不成对生物功能的创新生物打印平台允许制造复杂的，充满细胞的自由形式的构建体，该构建体最终可用于开发无异种3D组织模型以进行体外研究，或开发组织和器官替代物以用于临床应用。HUink中的细胞因子和粘附蛋白可促进细胞扩散和增殖，从而刺激细胞分泌的细胞外基质的快速产生。这种具有不成对生物功能的创新生物打印平台允许制造复杂的，充满细胞的自由形式的构建体，该构建体最终可用于开发无异种3D组织模型以进行体外研究，或开发组织和器官替代物以用于临床应用。HUink中的细胞因子和粘附蛋白可促进细胞扩散和增殖，从而刺激细胞分泌的细胞外基质的快速产生。这种具有不成对生物功能的创新生物打印平台允许制造复杂的，充满细胞的自由形式的构建体，该构建体最终可用于开发无异种3D组织模型以进行体外研究，或开发组织和器官替代物以用于临床应用。