Slow hydrogel matrix degradation enhances salivary gland mimetic phenotype

Mereness, Jared A.; Piraino, Lindsay; Chen, Chiao Yun; Moyston, Tracey; Song, Youhong; Shubin, Andrew D.; DeLouise, Lisa A.; Ovitt, Catherine E.; Benoit, Danielle S. W.

doi:10.1016/j.actbio.2023.05.005

Cited by 6 publications

(2 citation statements)

References 108 publications

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“…112 More recently, slow degradability of ECM hydrogels has been attributed to promoting maintenance of adult SG phenotype and function in microculture systems. 113 Additionally, SGs develop through branching morphogenesis, a key process which requires specific ECM components (for example: laminin, fibronectin, etc.) within permissible matrix to allow coordinated signaling for cell proliferation, migration, and reorganization.…”

Section: -Human Parotid Epithelial Cells (Hpecs)mentioning

confidence: 99%

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

Pillai,

Munguia-Lopez,

Tran

2024

ACS Appl. Bio Mater.

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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.

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Section: -Human Parotid Epithelial Cells (Hpecs)mentioning

confidence: 99%

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

Pillai,

Munguia-Lopez,

Tran

2024

ACS Appl. Bio Mater.

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“…11 The rate of bulk hydrogel degradation can vary by cell type, 12 donor age, 13 and cell seeding density, 14 which introduces experimental variability in the time-dependent properties of synthetic matrices. A variety of crosslinking peptides have been used to tune how cells degrade the gels, such as increasing or decreasing the rate of bulk hydrogel degradation, 5,15,16 control cell migration by cell type, 12,17 or mimic the combine several peptides to mimic the complex environment found in tissues. 18 Most peptide-cross linked hydrogels are degraded by soluble MMPs which can diffuse over 100 µm from the surface of cells and induce bulk degradation of matrices (Fig.…”

Section: Introductionmentioning

confidence: 99%

Optimizing Peptide Crosslinks for Cell-Responsive Hydrogels

Wu,

Rozans,

Moghaddam

et al. 2024

Preprint

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Cells dynamically modify their local extracellular matrix by expressing proteases that degrade matrix proteins. This enables cells to spread and migrate within tissues, and this process is often mimicked in hydrogels through the incorporation of peptide crosslinks that can be degraded by cell-secreted proteases. However, the cleavage of hydrogel crosslinks will also reduce the local matrix mechanical properties, and most crosslinking peptides, such as the widely used GPQGIWGQ "PanMMP" sequence, lead to bulk degradation of the hydrogel. A subset of proteases are localized to the cell membrane and are only active in the pericellular region in the immediate vicinity of the cell surface. These membrane-type proteases have important physiological roles and enable cells to migrate within tissues. In this work we developed an approach to identify and optimize peptide sequences that are specifically degraded by membrane-type proteases. We utilized a proteomic screen to identify peptide targets, and coupled this with a functional assay that both quantifies peptide degradation by individual cell types and can elucidate whether the peptides are primarily cleaved by soluble proteases or membrane-type proteases. We then used a split-and-pool synthesis approach to generate more than 300 variants of the target peptide to improve the degradation behavior. We identified an optimized peptide sequence, KLVADLMASAE, which is primarily degraded by membrane-type proteases, but enables both endothelial cells and stem cells grown in KLVADLMASAE-crosslinked hydrogels to spread and have viabilities similar to the gels crosslinked by the PanMMP peptide. Notably, the biological performance of the KLVADLMASAE peptide-cross linked gels was significantly improved from the initial peptide target found in the proteomic screen. This work introduces a functional approach to identifying and refining protease-substrate peptides as a way to enhance the properties of hydrogel matrices.

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A self-adapting woven net trap based on the evolution mechanism of orb-web topology

Lin,

Chou,

et al. 2024

Acta Biomaterialia

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Slow hydrogel matrix degradation enhances salivary gland mimetic phenotype

Cited by 6 publications

References 108 publications

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

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

Optimizing Peptide Crosslinks for Cell-Responsive Hydrogels

A self-adapting woven net trap based on the evolution mechanism of orb-web topology

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