Macrophage Adhesion and Phenotypic Shifts on Hydrophobically Modified Hydrogels

46 Pages Posted: 10 Oct 2019

See all articles by Zihao Xu

Zihao Xu

Iowa State University - Department of Materials Science and Engineering

Doh-Gyu Hwang

Iowa State University - Department of Materials Science and Engineering

Michael D. Bartlett

Iowa State University - Department of Materials Science and Engineering

Shan Jiang

Iowa State University - Department of Materials Science and Engineering; Government of the United States of America - Division of Materials Sciences and Engineering

Kaitlin M. Bratlie

Iowa State University - Department of Materials Science and Engineering; Iowa State University - Department of Chemical & Biological Engineering

Abstract

A balance of macrophage phenotypes is essential in successful implantation. Therefore, biomaterials should be carefully designed to better regulate the response of macrophages. We demonstrate macrophage adhesion and phenotypic shifts can be modulated with hydrophobically modified hydrogels. This study represents a fundamental concept in controlling cell adhesion and differentiation with substrate hydrophobicity. Gel synthesis was carried out using methacrylated gellan gum (MGG), which was polymerized and crosslinked through a photo-initiated thiol-ene reaction in situ. The degree of hydrophobicity was controlled by attaching hydrophobic branches of different lengths to the MGG. The attachment was carefully controlled so that the hydrogel compressive modulus was not affected by the hydrophobic modification. Compared to unmodified MGG, the water contact angle increased and the swelling ratio decreased for modified MGG hydrogels. Naïve and activated macrophages were subsequently seeded on the hydrogels with different surface wettability. Cell proliferation and spreading increased with increasing surface hydrophobicity. Hydrogel surface adhesion to a hydrophobic probe was quantified and showed an increasing trend with increasing substrate hydrophobicity. This suggests that the hydrophobic surface may increase protein adsorption, which, in turn, increases cell spreading. Cytokine secretion by M1 and M2 macrophages were also altered by substrate hydrophobicity. Both nitrite production, a marker of M1, and urea production, a marker of M2, increased with substrate hydrophobicity, with nitrate production being more pronounced. RAW 264.7 macrophages seeded on these substrates shifted to a more pro-inflammatory phenotype with increasing substrate hydrophobicity.

Keywords: gellan gum, hydrogels, macrophage polarization, surface modification

Suggested Citation

Xu, Zihao and Hwang, Doh-Gyu and Bartlett, Michael D. and Jiang, Shan and Bratlie, Kaitlin M., Macrophage Adhesion and Phenotypic Shifts on Hydrophobically Modified Hydrogels. Available at SSRN: https://ssrn.com/abstract=3464636 or http://dx.doi.org/10.2139/ssrn.3464636

Zihao Xu

Iowa State University - Department of Materials Science and Engineering

Ames, IA 50011-2063
United States

Doh-Gyu Hwang

Iowa State University - Department of Materials Science and Engineering

Ames, IA 50011-2063
United States

Michael D. Bartlett

Iowa State University - Department of Materials Science and Engineering

Ames, IA 50011-2063
United States

Shan Jiang

Iowa State University - Department of Materials Science and Engineering ( email )

Ames, IA 50011-2063
United States

Government of the United States of America - Division of Materials Sciences and Engineering ( email )

United States

Kaitlin M. Bratlie (Contact Author)

Iowa State University - Department of Materials Science and Engineering ( email )

Ames, IA 50011-2063
United States

Iowa State University - Department of Chemical & Biological Engineering ( email )

United States

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