IADR Abstract Archives
Organ-on-a-Chip Device Enables Reconstruction of Lamina Propria and Oral Mucosa Equivalents
Objectives: Advances in the field of tissue engineering and microfluidics have provided opportunities to develop next-generation tools such as ‘Organ-on-a-Chip’ devices. These are miniaturized devices that contain hollow microchannels and microchambers that can host living cells, micro-tissues and allow controlled delivery of media, drugs, and microbiome. Controlled perfusion through microchannels enables the supply of nutrients and delivery of drugs, test substances, or even microbes to the cells or tissues in a highly regulated spatiotemporal manner.
In this study, we developed an organ-on-a-chip device to reconstruct tissue equivalents representative of lamina propria (LPE) and oral mucosa (OME) and investigated its potential for drug permeation studies.
Methods: Using microfabrication technology, we fabricated an organ-on-a-chip device that contains an array of microchambers and microchannels. The microchambers were used to culture LPEs and OMEs. LPEs were fabricated by seeding oral fibroblasts embedded in a fibrin-based matrix within the culture chamber of the organ-on-a-chip device. OMEs were fabricated by seeding oral keratinocytes over LPE. The LPEs and OMEs cultured within the organ-on-a-chip device were characterized by immunohistology. Drug permeation studies were conducted using dental anesthetics as model drugs.
Results: The organ-on-a-chip device enabled the development of lamina propria and oral mucosa-like tissues. Histological sections of LPEs demonstrated the expression of vimentin-positive oral fibroblasts embedded within a collagen-1 and fibronectin rich lamina propria-like matrix. Similarly, the OMEs demonstrated a multilayered squamous epithelium over a cellular lamina propria. The mucosal epithelium demonstrated the expression of stratified epithelial cytokeratins (CK5, CK13, CK19, CK10) and barrier proteins (filaggrin and loricrin). Drug permeation studies demonstrated that lidocaine and articaine are more permeable through LPEs than OMEs.
Conclusions: Organ-on-a-chip technology provides a miniaturized platform to culture oral mucosal tissue equivalents and conducts downstream permeation studies. In the future, it can be used to study host-microbiome interactions, to assess the toxicity and biocompatibility of dental biomaterials and oral-care products.
In this study, we developed an organ-on-a-chip device to reconstruct tissue equivalents representative of lamina propria (LPE) and oral mucosa (OME) and investigated its potential for drug permeation studies.
Methods: Using microfabrication technology, we fabricated an organ-on-a-chip device that contains an array of microchambers and microchannels. The microchambers were used to culture LPEs and OMEs. LPEs were fabricated by seeding oral fibroblasts embedded in a fibrin-based matrix within the culture chamber of the organ-on-a-chip device. OMEs were fabricated by seeding oral keratinocytes over LPE. The LPEs and OMEs cultured within the organ-on-a-chip device were characterized by immunohistology. Drug permeation studies were conducted using dental anesthetics as model drugs.
Results: The organ-on-a-chip device enabled the development of lamina propria and oral mucosa-like tissues. Histological sections of LPEs demonstrated the expression of vimentin-positive oral fibroblasts embedded within a collagen-1 and fibronectin rich lamina propria-like matrix. Similarly, the OMEs demonstrated a multilayered squamous epithelium over a cellular lamina propria. The mucosal epithelium demonstrated the expression of stratified epithelial cytokeratins (CK5, CK13, CK19, CK10) and barrier proteins (filaggrin and loricrin). Drug permeation studies demonstrated that lidocaine and articaine are more permeable through LPEs than OMEs.
Conclusions: Organ-on-a-chip technology provides a miniaturized platform to culture oral mucosal tissue equivalents and conducts downstream permeation studies. In the future, it can be used to study host-microbiome interactions, to assess the toxicity and biocompatibility of dental biomaterials and oral-care products.