Dry mouth, or xerostomia, caused by salivary gland dysfunction significantly impacts oral/systemic health and quality of life. Although in vitro-generated artificial salivary glands have been considered as the fundamental solution, its structural complexity is difficult to reproduce using current biomaterials. Therefore, understanding and recapitulating the roles of biomacromolecules in salivary gland organogenesis is needed to solve these problems. Hyaluronic acid (HA) is a macromolecule abundant during salivary gland organogenesis, but its role remains unknown. Here, we verify the effects of HA on salivary gland organogenesis and artificial organ germ formation in solubilized and substrate-immobilized forms. In embryonic submandibular glands (eSMG), we found dense HA layers encapsulating proliferative c-Kit+ progenitor cells that were expressing CD44, an HA receptor. The blockage of HA synthesis, or degradation of HA, impaired eSMG growth by ablating the c-Kit+ progenitor cell population. We also found that high-molecular-weight (HMW) HA has a significant role in eSMG growth. Based on these findings, we discovered that HA is also crucial for in vitro formation of salivary gland organ germs, one of the most promising candidates for salivary gland tissue regeneration. We significantly enhanced salivary gland organ germ formation by supplementing HMW HA in solution; this effect was further increased when the HMW HA was immobilized on the substrate by polydopamine/HA co-immobilization. Our study suggests that the current use of HA in salivary gland tissue engineering can be further optimized.

唾液腺功能障碍引起的口干或口干症会严重影响口腔/全身健康和生活质量。虽然在体外人工唾液腺已被认为是基本的解决方案，其结构复杂性难以使用当前的生物材料来再现。因此，需要了解并概括生物大分子在唾液腺器官发生中的作用以解决这些问题。透明质酸（HA）是唾液腺器官发生过程中大量存在的大分子，但其作用仍然未知。在这里，我们验证了HA对唾液腺器官发生和溶解和基质固定形式的人工器官胚形成的影响。在胚胎下颌腺（eSMG）中，我们发现了密集的HA层，封装了表达CD44（HA受体）的增殖性c-Kit +祖细胞。HA合成的阻滞或HA的降解，通过消融c-Kit +祖细胞群体损害eSMG的生长。我们还发现，高分子量（HMW）HA在eSMG生长中具有重要作用。根据这些发现，我们发现医管局对于唾液腺器官细菌的体外形成，唾液腺组织再生的最有希望的候选者之一。通过在溶液中补充HMW HA，我们显着增强了唾液腺器官细菌的形成；当通过聚多巴胺/ HA共固定将HMW HA固定在底物上时，该效果进一步增强。我们的研究表明，目前在唾液腺组织工程中使用HA的方法可以进一步优化。