Bioengineering Division, Draper, Cambridge, MA, USA.
Colgate-Palmolive Company, Piscataway, NJ, USA.
Commun Biol. 2023 Jan 23;6(1):92. doi: 10.1038/s42003-023-04434-9.
Nearly half of American adults suffer from gum disease, including mild inflammation of gingival tissue, known as gingivitis. Currently, advances in therapeutic treatments are hampered by a lack of mechanistic understanding of disease progression in physiologically relevant vascularized tissues. To address this, we present a high-throughput microfluidic organ-on-chip model of human gingival tissue containing keratinocytes, fibroblast and endothelial cells. We show the triculture model exhibits physiological tissue structure, mucosal barrier formation, and protein biomarker expression and secretion over several weeks. Through inflammatory cytokine administration, we demonstrate the induction of inflammation measured by changes in barrier function and cytokine secretion. These states of inflammation are induced at various time points within a stable culture window, providing a robust platform for evaluation of therapeutic agents. These data reveal that the administration of specific small molecule inhibitors mitigates the inflammatory response and enables tissue recovery, providing an opportunity for identification of new therapeutic targets for gum disease with the potential to facilitate relevant preclinical drug efficacy and toxicity testing.
近一半的美国成年人患有牙龈疾病，包括牙龈组织的轻度炎症，即牙龈炎。目前，治疗方法的进步受到对生理相关血管化组织中疾病进展的机制理解不足的阻碍。为了解决这个问题，我们提出了一种高通量的微流控器官芯片模型，其中包含角化细胞、成纤维细胞和内皮细胞的人类牙龈组织。我们展示了该三细胞培养模型表现出了生理组织结构、黏膜屏障形成以及数周内的蛋白质生物标志物表达和分泌。通过炎症细胞因子的给药，我们证明了通过屏障功能和细胞因子分泌的变化来测量炎症的诱导。在稳定的培养窗口内的不同时间点诱导这些炎症状态，为评估治疗剂提供了一个强大的平台。这些数据表明，特定小分子抑制剂的给药减轻了炎症反应并促进了组织恢复，为牙龈疾病的新治疗靶点的鉴定提供了机会，有可能促进相关的临床前药物功效和毒性测试。
