唾液腺（SG）替代疗法仍未满足临床需求。由于SG损伤或疾病，如放射治疗（RT）引起的口头和颈部鳞状细胞癌（HNSCC）导致的唾液分泌减少而导致干燥口腔（“干嘴”）可能会产生。目前，对于口干症只存在姑息治疗方法，许多患者遭受口腔健康恶化和生活质量差的困扰。组织工程学可以通过在RT前分离健康的SG组织，体外扩增其细胞，并重建功能性的唾液腺-新腺体，以进行RT后植入，从而为SG替代提供永久解决方案。三维生物打印方法可以促进细胞沉积到基于水凝胶的定义结构中，模仿SG复杂分支发生过程中产生的薄上皮层。通过利用基于微流体的生物打印机与同轴聚合物和交联剂流，我们制造了薄而适应性的水凝胶结构，重现了SG薄上皮层的特征。这个灵活的平台实现了两种打印模式：我们制造了直径小于100 μm的固体水凝胶纤维，可以以栅格方式生成更大的毫米级结构。通过第二种方法，我们生成了壁厚范围为45-80 μm的空心管道，总管道直径跨度为0.6-2.2 mm，并验证了管道通畅性。在这两种情况下，SG细胞可以打印在薄水凝胶结构内，其表型得到了保留，并且在高密度（5.0 × 106 cells/mL）下具有高生存率。我们的研究展示了在多个长度尺度上对水凝胶结构的控制，并通过创建微观组织工程组件的新范式来解决SG恢复问题。Copyright © 2023. Published by Elsevier B.V.

Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar death caused by radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC). Currently, only palliative treatments exist for xerostomia, and many patients endure deteriorated oral health and poor quality of life. Tissue engineering could offer a permanent solution for SG replacement by isolating healthy SG tissues prior to RT, expanding its cells in vitro, and recreating a functional salivary neogland for implantation post-RT. 3D bioprinting methods potentiate spatial cell deposition into defined hydrogel-based architectures, mimicking the thin epithelia developed during the complex branching morphogenesis of SG. By leveraging a microfluidics-based bioprinter with coaxial polymer and crosslinker streams, we fabricated thin, biocompatible, and reproducible hydrogel features that recapitulate the thin epithelia characteristics of SG. This flexible platform enabled two modes of printing: we produced solid hydrogel fibers, with diameters <100 μm, that could be rastered to create larger mm-scale structures. By a second method, we generated hollow tubes with wall thicknesses ranging 45-80 μm, total tube diameters spanning 0.6-2.2 mm, and confirmed tube patency. In both cases, SG cells could be printed within the thin hydrogel features, with preserved phenotype and high viability, even at high density (5.0 × 106 cells/mL). Our work demonstrates hydrogel feature control across multiple length scales, and a new paradigm for addressing SG restoration by creating microscale tissue engineered components.Copyright © 2023. Published by Elsevier B.V.