Influence Of Polymer Surface Chemistry On The Recruitment Of Stem Cells In Mice
Abstract
The most troublesome biological response to the implantation of bloodcontacting
biomaterials is inflammation, which thereby-sets in motion a cascade of
adverse host responses. If devices for therapy and drug delivery could be developed that
prevent such responses from occurring altogether, a new generation of "stealth"
biomaterials would be born. Such was the motivation of this project, which sought to
investigate using mouse subcutaneous implantation model, the implant mediated host
tissue responses to surfaces differing in their functionalities. During the course of a
previous study in our laboratory, we accidentally discovered the presence of stem cells
and their accumulation at the capsule around microparticle implants.31 In our present
study, as the recruitment of stem cell coincided with that of the inflammatory cells, we
believe that stem cells get actively recruited by the inflammatory response induced by the biomaterial implantation. As the first stage of our investigation, to test this
hypothesis, we evaluated the host tissue responses to polypropylene particles with
surfaces, modified using radio frequency glow discharge plasma polymerization to have
high concentrations of -OH, -NH2, -CF3 and -COOH groups. The extent of
inflammatory responses mediated by the biomaterial implantation and corresponding
stem cell recruitment were assessed following implantation, using immunohistological
analyses.
Our results indicate that surface functionalities significantly affect both capsule
formed around the implant and the inflammatory cells, with leukocyte marker CD11b,
recruited to the implant. In addition, we have also uncovered many cells that stain
positive with stem cell markers SCF, Nanog and SH2B. Our results reveal that chemical
characteristics of material surfaces play important roles in biomaterial mediated tissue
responses. Surfaces with -NH2 and -OH groups showed the highest number of
inflammatory cells at the capsule along with the thickest capsule measured in microns.
Interestingly, we observed that all five surfaces provoked different extents of
recruitment of these stem cells at the capsule. The -COOH group showed the maximum
number of positive cells for all three stem cell markers. Unexpectedly, an inverse
relation between recruited inflammatory and stem cells was found for most surfaces ,
suggesting that stem cells are different and distinct from the inflammatory cells, though
both were influenced by the implant mediated foreign body response. The underlying
mechanism is yet to be determined. Overall, our results indicate that the surface functional groups influence not only the inflammatory responses but also the biomaterial mediated stem cell recruitment, inside the host.