Tissue Engineering of Salivary Glands through Biofabrication

Radiation therapy (RT) is a standard treatment for patients with head-and-neck cancers. Although highly effective at treating disease, RT inevitably causes secondary damage to the adjacent salivary glands (SG), leading to progressive and permanent loss of saliva production within weeks of treatment. The resultant sensation of xerostomia – or extreme “dry mouth” – and the measurable hyposalivation directly result from irrecoverable damage to the salivary acini, which generates both the fluid and enzymes in saliva. Impacts on speech, digestion, and oral cavity health significantly decrease quality of life. Restoration of a functional SG is a challenging target, as the glands are highly branched epithelia with multiple differentiated cell types and thin layers. The culture of primary SG cells in bulk hydrogels does not produce branched structures, and standard extrusion-based bioprinting methods lose spatial stability with soft hydrogels. Our laboratory has approached these issues through novel techniques, including coaxial microfluidic bioprinting, FRESH support bath printing, and multiphoton-based subtractive patterning. Employing these methods, with customized hydrogels and primary human cells, advances our opportunity to restore functional, organized systems to patients.