Monocyte/macrophage and protein interactions with non-fouling plasma polymerized tetraglyme and chemically modified polystyrene surfaces: In vitro and in vivo studies

Biomaterials become encapsulated by fibrous tissues after implantation in soft tissues. Monocytes and macrophages are believed to play important roles in this response. The hypothesis tested in this dissertation is that material surface chemistry determines the amount of adsorbed proteins, which mediate monocyte adhesion, activation, and the foreign body response. On chemically modified polystyrene surfaces, monocyte adhesion in vitro was promoted by preadsorbed fibrinogen, fibronectin, and IgG, and increased with increasing amount of adsorbed fibrinogen. Adsorbed proteins and material surface chemistry mediated monocyte activation. TNFα release, procoagulant activity, and multinucleated foreign body giant cell (FBGC) formation was at least two-fold higher on IgG than other protein adsorbed surfaces. Adsorbed IgG and fibrinogen triggered monocyte intracellular calcium changes. FBGC formation was the highest on the hydrophobic polystyrene surface.; Materials that greatly reduce non-specific protein adsorption may reduce the foreign body response to implanted materials. Radio-frequency plasma polymerized tetraglyme (CH₃O(CH₂CH₂O)₄CH ₃) surfaces contained PEO-like chemical species and reduced fibrinogen adsorption to less than 10 ng/cm2. Monocyte adhesion to tetraglyme in vitro was also greatly reduced. Monocyte adhesion correlated linearly to the amount of adsorbed fibrinogen on a series of tetraglyme surfaces deposited at different plasma powers. Multivariate analysis using partial least squares regression identified the key surface spectra variables from electron spectroscopy for chemical analysis (ESCA) and time of flight secondary ion mass spectrometry (ToF-SIMS) that contributed to the non-fouling properties of tetraglyme. However, leukocyte adhesion to surfaces implanted subcutaneously in mice for 1 or 28 days did not correlate with protein adsorption and was higher on tetraglyme than the FEP control. Fibrous encapsulation to tetraglyme implanted for 28 days was not reduced. Neutrophil adhesion to tetraglyme from whole blood or in plasma was higher than FEP, but was lower than FEP from neutrophils in serum. Loosely bound proteins such as fibrinogen may contribute to leukocyte adhesion to tetraglyme. Overall, protein adsorption and monocyte adhesion to tetraglyme in vitro did not correlate with tissue responses in vivo. Further understanding of the mechanism of fibrous encapsulation is necessary for developing biocompatible materials that can inhibit the foreign body response and promote normal wound healing.