Abstract
The poorly vascularized fibrous capsule that develops around implantable biomedical devices (for drug delivery, biosensors, etc.) severely limits their applications. We tested the hypotheses that co-implantation of bone marrow–derived progenitor cells could stimulate the vascularization of implants. To assess the presence of functional peri-implant microvasculature, we developed a novel model of implanted device containing an oxygen (O2)-sensing spin probe (detectable using electron paramagnetic resonance) placed inside a nanoporous filter-limited capsule. These devices were implanted subcutaneously in C57/Bl6 mice alone, with the addition of a Matrigel plug in front of the filter, or with the addition of Matrigel containing equal proportions of c-kit+ and stem cell antigen-1+ bone marrow–derived cells. Implants partial pressure of O2 (pO2) were recorded non-invasively and periodically for up to 10 weeks. Tissue surrounding the implants was collected for immunohistochemistry. Initially, there were no differences in pO2 between the experimental groups. After 3 weeks, the devices supplied with progenitor cells showed more than twice the O2 concentrations as controls. This difference remained significant for 4 more weeks and then started to decrease slightly, still being 6 mmHg higher than in the controls at 10 weeks post-implantation. Collagen deposition was detected around the control implants, along with F4/80-positive macrophages and giant cells. In the plugs collected from the cell treatment group, we found an active process of adipogenesis, accompanied by neovascularization, and a highly vascularized adipose layer surrounding the implants. In conclusion, we successfully developed a cell therapy-type strategy to maintain vascularization around implanted devices using co-administration of bone marrow–derived progenitor cells, and we demonstrated a novel O2-sensing method to functionally monitor neovascularization in vivo.
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