Bioengineered Salivary Gland Microtissues─A Review of 3D Cellular Models and their Applications

Abstract

Salivary glands (SGs) play a vital role in maintaining oral health through the production and release of saliva. Injury to SGs can lead to gland hypofunction and a decrease in saliva secretion manifesting as xerostomia. While symptomatic treatments for xerostomia exist, effective permanent solutions are still lacking, emphasizing the need for innovative approaches. Significant progress has been made in the field of three-dimensional (3D) SG bioengineering for applications in gland regeneration. This has been achieved through a major focus on cell culture techniques, including soluble cues and biomaterial components of the 3D niche. Cells derived from both adult and embryonic SGs have highlighted key in vitro characteristics of SG 3D models. While still in its first decade of exploration, SG spheroids and organoids have so far served as crucial tools to study SG pathophysiology. This review, based on a literature search over the past decade, covers the importance of SG cell types in the realm of their isolation, sourcing, and culture conditions that modulate the 3D microenvironment. We discuss different biomaterials employed for SG culture and the current advances made in bioengineering SG models using them. The success of these 3D cellular models are further evaluated in the context of their applications in organ transplantation and in vitro disease modeling.

Unlocking the Future: Bioprinting Salivary Glands—From Possibility to Reality

“…Stem cells are a proven resource in tissue engineering because of their remarkable potential to differentiate into different cell lineages [ 3 , 9 ]. Both adult and embryonic salivary gland-derived cells have demonstrated key in vitro characteristics essential for constructing 3D models of salivary glands [ 20 ]. Dental pulp stem cells, classified as adult stem cells, offer distinct advantages as they can be easily obtained from extracted teeth.…”

“…Spheroids derived from oral mucosa have found utility in various oral disease models, with specific gingival spheroids serving as valuable tools for studying gingiva–bacteria interactions [ 24 ]. In the realm of salivary gland research, spheroids and organoids have emerged as indispensable platforms for investigating glandular pathophysiology [ 20 ]. These 3D culture models provide insights into optimal culture conditions and biomaterials conducive to the organization of dental stem cells (DSCs).…”

Growing Role of 3D In Vitro Cell Cultures in the Study of Cellular and Molecular Mechanisms: Short Focus on Breast Cancer, Endometriosis, Liver and Infectious Diseases

“…In today’s fast-paced world of life science and biomedical research, a large body of experimental evidence has clearly demonstrated the enormous potential of three-dimensional (3D) cell cultures for improving our understanding of cell biology and the molecular mechanisms underlying disease [ 1 , 2 , 3 ], for drugs development and testing [ 4 , 5 , 6 , 7 ], in regenerative medicine [ 8 , 9 ] and also in tissue engineering [ 1 ]. Research has focused heavily on developing protocols and fine-tuning new technological approaches to developing diverse 3D in vitro models, also in agreement with the 3Rs (Replacement, Reduction, Refinement) principles of the European Union [ 10 ].…”