Bioengineering in salivary gland regeneration

Abstract

Salivary gland (SG) dysfunction impairs the life quality of many patients, such as patients with radiation therapy for head and neck cancer and patients with Sjögren’s syndrome. Multiple SG engineering strategies have been considered for SG regeneration, repair, or whole organ replacement. An in-depth understanding of the development and differentiation of epithelial stem and progenitor cells niche during SG branching morphogenesis and signaling pathways involved in cell–cell communication constitute a prerequisite to the development of suitable bioengineering solutions. This review summarizes the essential bioengineering features to be considered to fabricate an engineered functional SG model using various cell types, biomaterials, active agents, and matrix fabrication methods. Furthermore, recent innovative and promising approaches to engineering SG models are described. Finally, this review discusses the different challenges and future perspectives in SG bioengineering.

The effect of gum chewing on xerostomia and salivary flow rate in elderly and medically compromised subjects: A systematic review and meta-analysis

“…In accordance with this proposition, the two studies of patents being treated for head, neck or oral cancers in the present review were unable detect a signi cant effect of gum chewing on unstimulated saliva ow rate [18,23]. In these cases, emerging treatments such as salivary gland regeneration, repair, or replacement may be more appropriate therapies [39,40].…”

3Din vitromodeling of the exocrine pancreatic unit using tomographic volumetric bioprinting

“…The geometrical and morphological features of a tissue can affect the cell functionality and therefore represent another crucial aspect to consider in the design of a biomimetic model 41,76 . Although different engineering strategies have been adopted to obtain tubular lumen structures [41][42][43]73,77 , they lack in fully creating the 3D acinar-and ductal-like geometry 42,73 or in incorporating the stromal component 43,78 . However, our model currently replicates the glandular structure with 5:1 rescaled dimensions as compared to the physiological human gland (diameter of acinar portion 200 µm, of duct portion 50 µm).…”

“…The developed model is the first to recapitulate the tumor-stroma interplay occurring in pancreatic cancer at early stages while also accurately reproducing the anatomical structure of the exocrine gland. The geometrical and morphological features of a tissue can affect the cell functionality and therefore represent another crucial aspect to consider in the design of a biomimetic model 44,95 . Although different engineering strategies have been adopted to obtain tubular lumen structures [44][45][46]83,96 , they fail in creating the 3D tubuloacinar gland geometry exhuastively 45,83 or in incorporating the stromal component 46,97 .…”

“…Heterotypic 3D spheroids, patient-derived organoids, cancer-on-a-chip platforms, and 3D biofabricated constructs are the currently available bioengineered 3D models mimicking the pancreatic tumor-stroma interplay 16 . However, only a few novel studies in literature focus on the development of biomimetic platforms reproducing the microanatomy (in terms of 3D architecture and cellular composition) of the exocrine pancreas and lack to resemble the native compartmentalized architecture of tumor microenvironment that is widely recognized to affect cell functionality and cancer-cell response to therapeutics [39][40][41] . In particular, the gland complex geometry has been reproduced in simplified ways by employing different techniques like viscous fingering and extrusion-based methods [42][43][44][45] , that have disadvantages such as the low reproducibility, throughput and shape fidelity.…”

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

“…18,28,32 A variety of natural, synthetic, and composite biomaterials have been employed to support SG cell growth in three-dimensional (3D) culture for extended periods and for use as transplantation scaffolds. 14,33,34 These advancements have also enhanced our understanding of the various SG cell types, including the diversity of stem/progenitor cell populations, which are crucial as treatment targets or for use in stem cell therapy. 35−37 Furthermore, efforts have been directed toward comprehending how ECM remodelling and the physicochemical properties of biomaterials influence the SG phenotype and secretory functions, which are paramount for successful clinical applications.…”