Abstract

PURPOSE: Vascularization is a major barrier to tissue engineering and macrophages are believed to be integral. We have developed a microsurgical approach which rapidly vascularizes an adjacent scaffold. In micropuncture (MP), the recipient blood vessel wall is precisely disrupted providing an immediate route for cell extravasation. Here, we evaluated scaffold vascularization and macrophage infiltration across vascular origins. We hypothesized that concurrent artery/vein MP results in greatest macrophage infiltration and vascularization. METHODS: MP was tested in the rat femoral artery (MPA), vein (MPV), artery and vein (MPA/V), and no MP (control). MPs were created just prior to scaffold implantation. At post-operative day (POD) 3 and 10, samples were analyzed using whole mount angiography and histology. Vascular density was computed using artificial intelligence. Endothelial cell (EC) and macrophage infiltration were quantified. RESULTS: Vascular density appeared concordant with EC infiltration with MPA/V resulting in the greatest increase. Maximum macrophage infiltration was noted in MPV at both timepoints followed by MPA/V. Both conditions hastened macrophage accumulation when compared to MPA and the control. CONCLUSION: Micropuncture creates a localized pro-angiogenic environment. Although MPA/V led to greatest vascularization, it is noteworthy that MPV is also substantially pro-angiogenic. This suggests that the vein primarily drives cellular and vascular changes. MP appears to offer a tailored microsurgical approach for angiogenic induction which may prove beneficial to reconstructive surgery and tissue engineering.

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