Date of Award
Open Access Dissertation
Doctor of Philosophy in Biomedical Engineering (PhD)
Administrative Home Department
Department of Biomedical Engineering
Committee Member 1
Committee Member 2
Committee Member 3
Implanted medical devices undergo complications the longer they remain in contact with tissue or blood. This rejection of foreign materials by our body is one of the largest reasons innovations in biomedical sensors and implanted technology are being held back. One means to hold off this unwanted response is through the utilization of nitric oxide (NO) releasing materials. Two unique NO releasing polymeric materials were synthesized and characterized before being implanted subcutaneously. Both NO releasing materials described used S-nitrosothiol (RSNO) chemistry as the main mechanism for NO release. The first material described covalently links an RSNO to the backbone of PVC while the second material has RSNOs covalently attached to a hyperbranched polyamidoamine (HPAMAM) molecule, which is then blended within a polymer matrix. A high reservoir of NO was observed in the NO releasing HPAMAM when compared to other NO releasing polymers.
The two materials (SNAP-PVC, SNAP-HPAMAM blended in PVC) were implanted subcutaneously and were tested versus control polymers that did not release NO; materials were explanted after 1 and 15 days and histological characterization was completed. The inflammatory response was then observed through histological analysis and NO demonstrated anti-inflammatory properties, specifically by observing the presence of cells marked with CD11b, CD163, and iNOS. Fibrosis was also a major inflammatory response carefully observed. NO releasing implants showed a much more resolved state of inflammation and wound healing while the controls demonstrated signs of chronic inflammation and increased number of pro-inflammatory cells. The long lasting SNAP-HPAMAM PVC NO releasing materials showed a large reduction in chronic inflammatory macrophages marked with iNOS with a slight upregulation in anti-inflammatory macrophages after 15 days of implantation. Compared to control PVC implants, a significant reduction in fibrosis was observed as the encapsulation thickness was 120.28±36.1 µm while SNAP-PVC was 74.20±29.9 µm and SNAP-HPAMAM was 38.68±21.0 µm. A trend was seen in the reduction of CD11b+ cells with an increase in NO from the implants, along with an increasing trend of CD163+ cells. The presence of chronic inflammatory iNOS cells was also greatly reduced with the increase of NO to the surrounding subcutaneous tissue.
Hopkins, Sean, "DEVELOPMENT OF HIGH CAPACITY HYPERBRANCHED NITRIC OXIDE DONORS FOR CONTROLLING SUBCUTANEOUS INFLAMMATION", Open Access Dissertation, Michigan Technological University, 2015.