Angiogenesis, or the formation of new blood vessels from the preexisting vasculature, is a key component in numerous physiologic and pathologic responses and has broad impact in many medical and surgical specialties. In this review, we discuss the key cellular steps which lead to the neovascularization of tissues, and highlight the main molecular mechanisms and mediators in this process. We include discussions on proteolytic enzymes, cell/matrix interactions, pertinent cell signaling pathways, and end with a survey of the mechanisms which lead to the stabilization and maturation of neovasculatures.

Blood stream infection (BSI) is a serious complication of hematopoietic stem cell transplantation (HSCT). The aim of this retrospective cohort analysis was to describe BSI after HSCT, and to assess the predictors and outcomes of BSI after HSCT using multivariable modeling. Of the 243 subjects transplanted, 56% received allogeneic HSCT and 106 (43.6%) developed BSI. Of the 185 isolates, 68% were Gram-positive cocci, 21% were Gram-negative bacilli (GNR) and 11% were fungi. Type of allogeneic HSCT was an independent risk factor for BSI (hazard ratio (HR) 3.26, 95% confidence interval (CI) 1.50, 7.07, P ¼ 0.01), as was the degree of HLA matching (HR 1.84, 95% CI 1.00, 3.37, P ¼ 0.05). BSI was a significant independent predictor of mortality after HSCT (HR 1.79, 95% CI 1.18, 2.73, P ¼ 0.007), after adjusting for acute graft-versus-host disease (GVHD) and allogeneic HSCT (both predicting death p3 months after HSCT). In contrast to the effects of acute GVHD and allogeneic HSCT, the effect of BSI was evident throughout the post-HSCT period. GNR BSI and vancomycin-resistant enterococcal BSI also were significantly associated with death. We concluded that BSI is a common complication of HSCT associated with increased mortality throughout the post-HSCT period.

Neovascularization can be categorized into two general processes: vasculogenesis and angiogenesis. Angiogenesis is the formation of new capillaries from pre-existing vessels, requiring growth factor driven recruitment, migration, proliferation, and differentiation of endothelial cells (ECs). Complex cell-cell and cell-extracellular matrix (ECM) interactions contribute to this process, leading finally to a network of tube-like formations of endothelial cells supported by surrounding mural cells. The study of angiogenesis has broad clinical implications in the fields of peripheral and coronary vascular disease, oncology, hematology, wound healing, dermatology, and ophthalmology, among others. As such, novel, clinically relevant models of angiogenesis in vitro are crucial to the understanding of angiogenic processes. We highlight some of the advances made in the development of these models, and discuss the importance of incorporating the three-dimensional cell-matrix and EC-mural cell interactions into these in vitro assays of angiogenesis. This review also discusses our own 3-D angiogenesis assay and some of the in vitro results from our lab as they relate to therapeutic neovascularization and tissue engineering of vascular grafts.

Cardiovascular disease continues to be the leading cause of death worldwide, and the prevalence of cardiovascular disease has reached epidemic proportions worldwide. Not surprisingly this has led to an increasing number of vascular procedures annually. Unfortunately, the success of these procedures over time continues to limit their long-term effects. Biomedical engineering approaches to improve upon current prosthetic grafts, developing new prosthetic grafts, and creating tissue engineered blood vessels for clinical application offer hope of improving the durability of vascular interventions and improving patients' treatment for cardiovascular disease.