Modulus-dependent macrophage adhesion and behavior

Abstract

Macrophage attachment and activation to implanted materials is crucial in determining the extent of acute and chronic inflammation, and biomaterials degradation. In an effort to improve implant performance, considerable attention has centered on altering material surface chemistry to modulate macrophage behavior. In this work, the influence of the modulus of a material on the behavior of model macrophages (i.e., human promonocytic THP-1 cells) was investigated. We synthesized interpenetrating polymer network (IPN) coatings with varying moduli to test the hypothesis that lower moduli surfaces attenuate THP-1 cell attachment and activation. The surface chemistry and moduli of the IPN coatings were characterized using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM), respectively. THP-1 cells preferentially attached to stiffer coatings of identical surface chemistry, confirming that fewer macrophages attach to lower moduli surfaces. The secretion of human TNF-alpha, IL-10, IL-8 and IL-1beta from THP-1 cells attached to the IPNs was measured to assess the concentration of both pro- and anti-inflammatory cytokines. The global amount of TNF-alpha released did not vary for IPN surfaces of different moduli; however, the amount of the pro-inflammatory cytokine IL-8 released demonstrated a biphasic response, where lower (approx. 1.4 kPa) and very high (approx. 348 kPa) moduli IPN surfaces attenuated IL-8 secretion. The different trends for TNF-alpha and IL-8 secretion highlight the complexity of the wound healing response, suggesting that there may not be a unique surface chemistry and substratum modulus combination that minimizes the pro-inflammatory cytokines produced by activated macrophages.

Indentation Versus Tensile Measurements of Young's Modulus for Soft Biological Tissues

“…For example, it has been shown that cellular behavior is influenced by the compliance of the substrate on which the cell resides. 15,16,18,20,23,29,[96][97][98][99][100][101] To accurately relate these laboratory observations back to in vivo cell function, compliance of the tissue and the matrix with which a cell interacts must be characterized. These values can be obtained with the AFM or The values are the averages without the suspected outliers.…”

Biocompatibility and inflammatory response in vitro and in vivo to gelatin-based biomaterials with tailorable elastic properties

“…This may be due to the rather low E-moduli of the materials (10e60 kPa), as earlier studies showed increasing macrophage attachment to materials with increasing Young's modulus, preferentially > 100 kPa [37]. Additionally, highly hydrophilic materials (like gelatin-based hydrogels) tend to show low macrophage adhesion [38].…”

Scleral Reinforcement Through Host Tissue Integration with Biomimetic Enzymatically Degradable Semi-Interpenetrating Polymer Network

“…[46][47][48] Specifically, soft substrates tend to inhibit cell spreading and slow migration compared to their stiffer counterparts 49,50 ; they also induce differentiation of mesenchymal stem cells to specific phenotypes. 51 In this study, a mechanical influence could explain both the delayed proliferation and slower overall rates of proliferation for cells cultured on edsIPN compared with TCPS.…”