Growth Factor Gradients in Migration-permissive Hydrogels for Salivary Gland Assembly
Medicine, Health Care Growth Factor Gradients in Migration-permissive…
Published: March 23, 2018.
Released by International American Associations for Dental Research
Alexandria, VA, USA – At the 47th Annual Meeting of the American Association for Dental Research (AADR), held in conjunction with the 42nd Annual Meeting of the Canadian Association for Dental Research (CADR), Kelsea Marie Hubka, a Rice University graduate student and visiting student at University of Texas Health Science Center School of Dentistry, Houston, Texas, presented a poster titled “Growth Factor Gradients in Migration-Permissive Hydrogels for Salivary Gland Assembly.” The AADR/CADR Annual Meeting is in Fort Lauderdale, Fla., USA from March 21-24, 2018.
Engineered 3D morphogen gradients in hydrogels can direct human salivary gland stem/progenitor cell (hS/PC) differentiation into ductal and acinar cell phenotypes for gland replacement and direct tissue organization during embryogenesis/tissue repair. Heparin-binding growth factor (HBGF) gradients form by release from matrix heparin sulfate proteoglycans such as perlecan at sites on heparan sulfate chains decorating N-terminal domain I (PlnD1). HBGFs, including the FGF family elicit both cell differentiation and motility. Gradients of HBGFs, PlnD1, and matrix components can be introduced into migration-permissive hydrogels made using a custom 3D-printed gradient maker device.
To allow the cells to form into structures that look like native tissue, the hydrogel system was modified with matrix molecules to provide sites for the cells to attach as they move. The chemical cross links were also partially replaced with biological ones that let the cells use their enzymes to cut through and clear space for movement. The extent of cell spreading and motility was assessed. hS/PCs were incorporated into these customized hydrogels with optimal crosslinking density where PlnD1 was introduced as a gradient using the 3D-printed gradient maker device at flow rate 0.9mL/min. After gradient hydrogels were crosslinked, growth factors FGF-7/10 were bound to PlnD1 to promote directional cell movement. Morphogenesis was assessed using confocal microscopy.
Human hS/PCs remained viable and assembled into acinar-like structures at each crosslinking density. PlnD1/HBGF gradients permitted greater hS/PC cell motility over time than PlnD1 gradients lacking growth factors.
The HA-based hydrogel with enzymatically-degradable crosslinkers for selective degradation and cell motility allowed for gland assembly. The growth factor gradients in PlnD1-modified migration-permissive hydrogels support salivary gland cell motility and can serve as instructive matrices for salivary gland tissue engineering.
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