Biomimetic bone-vessel interface-on-a-chip for simulating periodontal physiological and pathological microenvironment

Periodontitis is a chronic inflammatory disease affecting periodontal supporting tissues. Untreated, it causes irreversible alveolar bone destruction, ultimately leading to tooth loss. Periodontitis-associated pathogenic bacteria/metabolites and pro-inflammatory factors can initiate or exacerbate systemic disease through the circulation. Endothelial cells, forming the interface between circulation and tissues, play a key role in disease progression. As microfluidic organ chips enable the establishment of tissue-tissue interfaces and simulation of the <i>in vivo</i> microenvironment, we constructed a bone-vessel interface-on-a-chip. Within this physiological model, human bone marrow mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) were successfully co-cultured with high viability. HUVECs formed a confluent monolayer exhibiting selective vascular permeability. Osteo-differentiated hBMSCs expressed alkaline phosphatase, secreted bone-related proteins, and formed mineralized deposits. By introducing the <i>Porphyromonas gingivalis</i> (<i>P. gingivalis</i>) metabolite LPS and the pro-inflammatory factor TNF-α, we established an inflammatory microenvironment. The chip model subsequently exhibited vascular endothelial intercellular junction disruption, upregulated adhesion protein expression, enhanced monocyte adhesion, impaired vascular endothelial barrier function, and reduced bone-related protein expression. These results demonstrate that bone-vessel interface-on-a-chip can effectively study the effects of periodontitis metabolites and pro-inflammatory factors on the vascular barrier and bone tissue through controlled integration of biochemical and biophysical cues. This model provides a robust platform for investigating endothelial cell-targeted therapies for inflammatory diseases, including periodontitis and associated systemic diseases.