Impact of Exogenous Nitric Oxide Treatment on Vascularization of a Subcutaneous Device for Cell Transplantation

Abstract

Subcutaneous polymer scaffolds have shown potential for creating an optimal transplantation site in cellular replacement therapy, e.g., when transplanting insulin-producing cells to cure type 1 diabetes. Imperative for these scaffolds is a high degree of vascularization to guarantee long-term functional cellular survival. In this study, the effect of the nitric oxide (NO) donor S-nitroso-N-acetyl-dl-penicillamine (SNAP) on the vascularization degree of a subcutaneous poly(d,l-lactide-co-ε-caprolactone) (PDLLCL) scaffold was investigated. To this end, scaffolds were implanted under the skin of C57BL/6 mice. Each mouse received a control scaffold and a scaffold containing SNAP. At day 7, 14, and 28, the oxygen percentage within the scaffolds was measured and at day 28, the vascularization degree was determined with lectin infusion and gene expression analysis. We measured lower oxygen percentages within the scaffolds containing the NO-donor up to day 14 compared to the control scaffolds, but no differences were found at day 28. Although blood vessels in the scaffolds were well perfused, no differences between the groups were found in the lectin staining and gene expression of vascular markers, such as CD31, CD105, and VEGFa. To conclude, in this biomaterial setting, addition of a NO-donor did not improve the vascularization degree of the subcutaneous scaffold.