Open AccessPeptide‐Functionalized Hydrogels Modulate Integrin Expression and Stemness in Adult Human Epidermal Keratinocytes
Author(s) -
DavisHall Duncan,
Nguyen Vy,
D'Ovidio Tyler J.,
Tsai Ethan,
Bilousova Ganna,
Magin Chelsea M.
Publication year - 2019
Publication title -
advanced biosystems
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.153
H-Index - 18
ISSN - 2366-7478
DOI - 10.1002/adbi.201900022
Subject(s) - self healing hydrogels , keratinocyte , integrin , extracellular matrix , microbiology and biotechnology , fibronectin , laminin , tissue engineering , in vitro , regeneration (biology) , stem cell , chemistry , materials science , biomedical engineering , biology , cell , biochemistry , medicine , organic chemistry
The extracellular matrix (ECM) controls keratinocyte proliferation, migration, and differentiation through β‐integrin signaling. Wound‐healing research requires expanding cells in vitro while maintaining replicative capacity; however, early terminal differentiation under traditional culture conditions limits expansion. Here, a design of experiments approach identifies poly(ethylene glycol)‐based hydrogel formulations with mechanical properties (elastic modulus, E = 20.9 ± 0.56 kPa) and bioactive peptide sequences that mimic the epidermal ECM. These hydrogels enable systematic investigation of the influence of cell‐binding domains from fibronectin (RGDS), laminin (YIGSR), and collagen IV (HepIII) on keratinocyte stemness and β 1 integrin expression. Quantification of 14‐day keratin protein expression shows four hydrogels improve stemness compared to standard techniques. Three hydrogels increase β 1 integrin expression, demonstrating a positive linear relationship between stemness and β 1 integrin expression. Multifactorial statistical analysis predicts an optimal peptide combination ([RGDS] = 0.67 m m , [YIGSR] = 0.13 m m , and [HepIII] = 0.02 m m ) for maintaining stemness in vitro. Best‐performing hydrogels exhibit no decrease in Ki‐67‐positive cells compared to standards (15% decrease, day 7 to 14; p < 0.05, Tukey Test). These data demonstrate that precisely designed hydrogel biomaterials direct integrin expression and promote proliferation, improving the regenerative capability of cultured keratinocytes for basic science and translational work.