Abstract
Implant-mediated fibrotic reactions are detrimental to the performance of encapsulated cells, implanted drug release devices, and sensors. To improve the implant function and longevity, recent research has emphasized the need for inducing alterations in cellular responses. Although material surface functional groups have been shown to be potent in affecting cellular activity in vitro and short-term in vivo responses, these groups appear to have little influence on long-term in vivo fibrotic reactions, possibly as a result of insufficient interactions between recruited host cells and functional groups on the implants. To maximize the influence of functionality on cells, and to mimic drug release microspheres, functionalized micron-sized particles were created and tested for their ability in modulating tissue responses to biomaterial implants. In this work, the surfaces of polypropylene particles were controllably coated with four different functional groups, specifically -OH, -NH(2), -CF(x), and -COOH, using a radio frequency glow discharge plasma polymerization technique. The effect of these surface functionalities on host tissue responses were then evaluated using a mice subcutaneous implantation model. Major differences were observed in contrasting tissue response to the different chemistries. Surfaces with -OH and -NH(2) surface groups induced the thickest fibrous capsule accompanied with the greatest cellular infiltration into the implants. In contrast, surfaces with -CF(x) and -COOH exhibited the least inflammatory/fibrotic responses and cellular infiltrations. The present results clearly demonstrate that, by increasing the available functionalized surface area and spatial distribution, the effect of surface chemistry on tissue reactivity can be substantially enhanced.