Development of a Functional Salivary Gland Tissue Chip with Potential for High-content Drug Screening

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Mar 20

PMID 33742114

Citations 21

Authors

Yuanhui Song

Hitoshi Uchida

Azmeer Sharipol

Lindsay Piraino

Jared A Mereness

Matthew H Ingalls

Jonathan Rebhahn

Shawn D Newlands

Lisa A DeLouise

Catherine E Ovitt

Danielle S W Benoit

Affiliations

Soon will be listed here.

Abstract

Radiation therapy for head and neck cancers causes salivary gland dysfunction leading to permanent xerostomia. Limited progress in the discovery of new therapeutic strategies is attributed to the lack of in vitro models that mimic salivary gland function and allow high-throughput drug screening. We address this limitation by combining engineered extracellular matrices with microbubble (MB) array technology to develop functional tissue mimetics for mouse and human salivary glands. We demonstrate that mouse and human salivary tissues encapsulated within matrix metalloproteinase-degradable poly(ethylene glycol) hydrogels formed in MB arrays are viable, express key salivary gland markers, and exhibit polarized localization of functional proteins. The salivary gland mimetics (SGm) respond to calcium signaling agonists and secrete salivary proteins. SGm were then used to evaluate radiosensitivity and mitigation of radiation damage using a radioprotective compound. Altogether, SGm exhibit phenotypic and functional parameters of salivary glands, and provide an enabling technology for high-content/throughput drug testing.

Citing Articles

Advances in modeling periodontal host-microbe interactions: insights from organotypic and organ-on-chip systems.

Makkar H, Sriram G Lab Chip. 2025; 25(5):1342-1371.

PMID: 39963082 PMC: 11833442. DOI: 10.1039/d4lc00871e.

Microfluidic organ-on-chip systems for periodontal research: advances and future directions.

Sriram G, Makkar H Front Bioeng Biotechnol. 2025; 12:1490453.

PMID: 39840127 PMC: 11747509. DOI: 10.3389/fbioe.2024.1490453.

A single dose of radiation elicits comparable acute salivary gland injury to fractionated radiation.

Johnson A, Elder S, McKendrick J, Hegarty L, Mercer E, Emmerson E Dis Model Mech. 2024; 17(8).

PMID: 39086326 PMC: 11361643. DOI: 10.1242/dmm.050733.

Engineering models of head and neck and oral cancers on-a-chip.

da Costa Sousa M, Vignolo S, Franca C, Mereness J, Alves Fraga M, Silva-Sousa A Biomicrofluidics. 2024; 18(2):021502.

PMID: 38464668 PMC: 10919958. DOI: 10.1063/5.0186722.

A Systematic Review on Organ-on-a-Chip in PDMS or Hydrogel in Dentistry: An Update of the Literature.

Pierfelice T, DAmico E, Petrini M, Romano M, DArcangelo C, Sbordone L Gels. 2024; 10(2).

PMID: 38391432 PMC: 10887950. DOI: 10.3390/gels10020102.

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