Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

Abstract

Implant-associated fibrotic capsule formation presents a major challenge for the development of long term drug release microspheres and implantable sensors. Since material properties have been shown to affect in vitro cellular responses and also to influence short term in vivo tissue responses, we have thus assumed that the type and density of surface chemical groups would affect the degree of tissue responses to microsphere implants. To test this hypothesis, polypropylene particles with different surface densities of -OH and -COOH groups, along with the polypropylene control (-CH 2 groups) were utilized. The influence of functional groups and their surface densities on tissue reactions were analyzed using a mice subcutaneous implantation model. Our comparative studies included determination and correlation of the extents of fibrotic capsule formation, cell infiltration into the particles and recruitment of CD11b+ inflammatory cells for all of the substrates employed. We have observed major differences among microspheres coated with different surface functionalities. Surfaces with -OH surface groups trigger the strongest responses while -COOH rich surfaces prompt the least tissue reactions. However, variation of the surface density of either functional group has a relatively minor influence on the extent of fibrotic tissue reactions. The present results show that surface functionality can be used as a powerful tool to alter implant-associated fibrotic reactions and, potentially, to improve the efficacy and function of drug delivery microspheres, implantable sensors and tissue engineering scaffolds.

A macrophage/fibroblast co-culture system using a cell migration chamber to study inflammatory effects of biomaterials

“…This was observed in both macrophage mono-cultures and cocultures, illustrated by their accumulated distance, while macrophages on CH 3 and NH 2 SAMs had intermediate accumulated distances. It was reported elsewhere that OH-functionalized surfaces triggered a higher recruitment of CD11b+ cells and cell infiltration in animal implantation assays [71]. This could be related to the strong complement activation by OH groups via the alternative pathway activation [58] and could explain the higher motility of macrophages in the present study due to the presence of serum.…”

In vivo investigation of the inflammatory response against allylamine plasma polymer coated titanium implants in a rat model

“…However, the results from experiment day 56 of the present study indicate that the host response improves in the long term. Using a similar experimental design to that of Kamath et al (s.c. implantation of surface-modified polypropylene microspheres in mice), Nair et al recently demonstrated that variations in the surface density of OH and COOH groups deposited by plasma treatment had only a relatively minor influence on the extent of the foreign body reaction [22]. As outlined above, the experimental model in the present study is different from that used by Nair et al in a number of relevant aspects.…”

Surface chemistry influences cancer killing effect of TiO2 nanoparticles

“…Since it is well established that positive charged nanoparticles have high affinity to negative charged cell membrane protein [48], it is likely that JHU cell membranes were saturated with -NH 2 functionalized particles at lowest concentration (0.1 mg/ml) employed. In addition, using polypropylene microparticles [49], we find that the density of surface functionality has little influence on cell:particle interactions. Therefore, the increase in the surface NH 2 concentration, or the increased exposure to NH 2 groups in the case of nanoparticles, may not have a significant effect on cell survival.…”

“…Perhaps, the positive charged amine group prompts a destructive impact on the negatively charged membrane of the cells. The absence of a further decrease in cell viability may be explained by results from a recent study which shows that the properties of a surface functional group override the effects of increases in density or concentration of the functionality [49]. While the positive charged -NH 2 coating shows a significantly lower viability for JHU cells compared to uncoated TiO 2 , negatively charged -COOH coated particles have substantially higher cell viability levels except at potential overload concentrations.…”