Abstract-Bone marrow-derived cells contribute to physiological and pathological vascular remodeling throughout ontogenesis and adult life. During tissue regeneration and tumor growth, the release of cytokines and chemokines mediates the recruitment of hematopoietic and endothelial progenitor cells that contribute to the assembly of neovessels. Current evidence implies that platelets contribute structurally and instructively to vascular remodeling. Platelets adhere almost immediately to exposed or activated endothelium, and they are major storage and delivery vehicles for pro-and antiangiogenic growth factors including VEGF-A and thrombospondin (TSP), and cytokines and chemokines, such as stromal-derived factor 1 (SDF-1). By site-specific deployment of these factors, platelets orchestrate the local angiogenic stimulus within a tissue and direct the recruitment and differentiation of circulating bone marrow-derived cells. These insights have profound clinical implications; inhibition of platelet-deployed growth factors or their receptors may be an effective strategy to block tumor growth, whereas activation of these pathways may be used to accelerate revascularization and tissue regeneration.
Topical treatment of superficial wounds has many advantages including decreased cost and increased ease of application compared with systemic treatments. Many of the advantages, however, are lost when it is necessary for repeated doses of topical medications to be given over an extended period of time. Therefore, a drug-delivery vehicle that delivers biologically appropriate doses in a sustained fashion would prove valuable. In this study, an alginate hydrogel scaffold impregnated with the angiogenic chemokine stromal-derived factor-1 was used to provide targeted, though short-term, delivery directly into the wound bed. Wounds were created on the dorsum of mice, and either a stromal-derived factor-1-impregnated or a saline-impregnated scaffold was applied. Wounds were explanted after 1, 3, 7 days, wound area was measured, and histology and immunohistochemistry for endothelial markers were performed. The remaining wound area in stromal-derived factor-1-treated wounds vs. controls was not significant 1 day after wounding (96.7 ± 0.1 vs. 97.5 ± 1.1%, p=0.317), but was significant after 3 days postwounding (46.7 ± 0.1 vs. 82.3 ± 2.4%, p=0.046) and 7 days postwounding (2.3 ± 1.3 vs. 32.0 ± 4.0%, p=0.049). Immunohistochemistry revealed a greater degree of endothelial cell invasion into the wound bed infiltration compared with controls. The results of this study suggest significant clinical promise for our hydrogel-delivery vehicle in the treatment of wounds.
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