Organoids hold inestimable therapeutic potential in regenerative medicine and are increasingly serving as an in vitro research platform. Still, their expanding applications are critically restricted by the canonical culture matrix and system. Synthesis of a suitable bioink of bioactivity, biosecurity, tunable stiffness, and printability to replace conventional matrices and fabricate customized culture systems remains challenging. Here, we envisaged a novel bioink formulation based on decellularized extracellular matrix (dECM) from porcine small intestinal submucosa for organoids bioprinting, which provides intestinal stem cells (ISCs) with niche-specific ECM content and biomimetic microstructure. Intestinal organoids cultured in the fabricated bioink exhibited robust generation as well as a distinct differentiation pattern and transcriptomic signature. This bioink established a new co-culture system able to study interaction between epithelial homeostasis and submucosal cells and promote organoids maturation after transplantation into the mesentery of immune-deficient NODSCID-gamma (NSG) mice. In summary, the development of such photo-responsive bioink has the potential to replace tumor-derived Matrigel and facilitate the application of organoids in translational medicine and disease modeling.

中文翻译：

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细胞外基质生物墨水作为生物安全基质胶替代品可增强干性并促进肠道类器官的移植

类器官在再生医学中具有不可估量的治疗潜力，并且越来越多地用作体外研究平台。尽管如此，它们不断扩展的应用仍受到规范文化矩阵和系统的严重限制。合成具有生物活性、生物安全性、可调刚度和可印刷性的合适生物墨水来替代传统基质和制造定制培养系统仍然具有挑战性。在这里，我们设想了一种基于猪小肠粘膜下层脱​​细胞细胞外基质 (dECM) 的新型生物墨水配方，用于类器官生物打印，它为肠道干细胞 (ISC) 提供了生态位特异性 ECM 含量和仿生微结构。在制造的生物墨水中培养的肠道类器官表现出强大的生成能力以及独特的分化模式和转录组学特征。这种生物墨水建立了一个新的共培养系统，能够研究上皮稳态和粘膜下细胞之间的相互作用，并在移植到免疫缺陷型 NODSCID-γ (NSG) 小鼠的肠系膜后促进类器官成熟。总之，这种光响应生物墨水的开发有可能取代肿瘤来源的基质胶，并促进类器官在转化医学和疾病建模中的应用。