Neutrophil interaction with distinct moeties in biomimetic hydrogels
The focus of this study is to use tissue-engineering methods to evaluate the mechanics of the neutrophil interactions with the extracellular matrix. Specifically, we use a (poly)ethylene glycol (PEG) polymer to form a polymerized hydrogel that serves as a biologically inert surface. By grafting bioactive moieties onto the PEG chain, the hydrogel is made bioactive. The moeties incorporated into the hydrogel are adhesive peptides that are known to interact with receptors on the surface of the neutrophil. The goal of this work is to define the mechanisms by which these engineered elements influence the interactions of neutrophils with this biomaterial. The overall goal of this work is to define the mechanisms by which these engineered elements influence the interactions of neutrophils with this clinically useful biomaterial. The current experiments analyze the interactions of isolated human neutrophils with PEG hydrogels with incorporated arginine-glycine-aspartic acid-serine, RGDS, a known peptide ligand for some β1 and β3 integrins, and threonin-methionine- lysine-isoleucine-isoleucine-proline-phynalanine-asparaginearginine-leucine- threonine-isoleucine-glycine-glycine, TMKIIPFNRLTIGG, a peptide ligand for one member of the β2 integrin family (CD11b/CD18, Mac-1). Our results demonstrate that neutrophils, with or without chemotactic stimulation, show little ability to adhere to PEG hydrogels without incorporated peptides. Incorporating distinct bioactive peptides either alone or in combination has enabled recognition of differential functions of αvβ3, β1 and β2 integrins on cell adhesion, spreading and locomotion. Combined interactions result in activity that differs markedly from that seen with either integrin independently engaged. This experimental model not only allows investigation of leukocyte functions induced through interactions with isolated, defined ligands but allows the development of engineered matrices with defined bioactive properties regarding aspects of innate immunity.
Gonzalez, AG; Gobin, A; West, J; McIntire, LV; Smith, CW
Transactions 7th World Biomaterials Congress
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