Abstract
Introduction: Artificial tissue can restore function in failing organs. Engraftment of artificial tissue requires a coordinated interaction between the implanted material and the host innate immune response. Macrophages regulate the host-material interaction immediately following implantation, and these cells influence downstream scaffold vascularization by displaying a multi-phase response that first primes the environment and then remodels ongoing regenerative processes. We investigated a novel approach for user-controlled immunomodulation after implantation that relies on material-delivered cyclic strain. We hypothesized that cyclic strain applied during early priming phases will impact the mechanosensitive host-macrophage population by enhancing the classically activated (M1) phenotype and promoting downstream angiogenesis.
Methods and Results: We used magnetically responsive scaffolds in combination with an alternating uniform magnetic field to deliver cyclic strain to scaffold associated cells. Cell-free scaffolds were subcutaneously implanted into male, BALB/c mice, N=5. Mice were exposed to a magnetic field (30 Gauss, 0.5Hz) during the early (day 1-3 post-implantation (p.i.)), middle (day 5-8 p.i.), or late (day 12-15 p.i.) phase of the host macrophage response or kept as unexposed controls. Magnetically actuated scaffolds at day 5-8 p.i. showed an increase in the percentage of cells expressing the macrophage marker F4/80 (67.4% ± 2.29 stimulated vs. 58.9% ± 1.05 control (p<0.05), n=5). Furthermore, we observed an increase in the percentage of macrophages expressing the M1 marker CD86 (37.5% ± 2.93 stimulated vs. 23.4% ± 2.78 control (p<0.05), n=5) by t-test. To assess scaffold vascularization at day 21 p.i., we quantified the number of perfused blood vessels on histological samples. Magnetic stimulation during the early (1.25 vessels/mm2 ± 0.38 (p=0.052), n=10) or middle (1.22 vessels/mm2 ± 0.32 (p=0.059), n=10) phase promoted angiogenesis compared to control (0.25 vessels/mm2 ± 0.16, n=7) using the Kruskal-Wallis test.
Conclusions: We demonstrate that user-controlled, mechanically active materials can modulate the host-macrophage response after implantation and promote angiogenesis.
Methods and Results: We used magnetically responsive scaffolds in combination with an alternating uniform magnetic field to deliver cyclic strain to scaffold associated cells. Cell-free scaffolds were subcutaneously implanted into male, BALB/c mice, N=5. Mice were exposed to a magnetic field (30 Gauss, 0.5Hz) during the early (day 1-3 post-implantation (p.i.)), middle (day 5-8 p.i.), or late (day 12-15 p.i.) phase of the host macrophage response or kept as unexposed controls. Magnetically actuated scaffolds at day 5-8 p.i. showed an increase in the percentage of cells expressing the macrophage marker F4/80 (67.4% ± 2.29 stimulated vs. 58.9% ± 1.05 control (p<0.05), n=5). Furthermore, we observed an increase in the percentage of macrophages expressing the M1 marker CD86 (37.5% ± 2.93 stimulated vs. 23.4% ± 2.78 control (p<0.05), n=5) by t-test. To assess scaffold vascularization at day 21 p.i., we quantified the number of perfused blood vessels on histological samples. Magnetic stimulation during the early (1.25 vessels/mm2 ± 0.38 (p=0.052), n=10) or middle (1.22 vessels/mm2 ± 0.32 (p=0.059), n=10) phase promoted angiogenesis compared to control (0.25 vessels/mm2 ± 0.16, n=7) using the Kruskal-Wallis test.
Conclusions: We demonstrate that user-controlled, mechanically active materials can modulate the host-macrophage response after implantation and promote angiogenesis.
| Original language | English GB |
|---|---|
| Article number | A10270 |
| Journal | Circulation |
| Volume | 140 |
| Issue number | 1 Supplement |
| State | Published - 2019 |