Nanoparticulate delivery of agents for induced elastogenesis in three-dimensional collagenous matrices.

The degradation of elastic matrix in the infrarenal aortic wall is a critical parameter underlying the formation and progression of abdominal aortic aneurysms. It is mediated by the chronic overexpression of matrix metalloprotease (MMP)-2 and MMP-9, leading to a progressive loss of elasticity and weakening of the aortic wall. Delivery of therapeutic agents to inhibit MMPs, while concurrently coaxing cell-based regenerative repair of the elastic matrix represents a potential strategy for slowing or arresting abdominal aortic aneurysm growth.

Impact of cyclic stretch on induced elastogenesis within collagenous conduits.

In vitro tissue engineering of vascular conduits requires a synergy between several external factors, including biochemical supplementation and mechanotranductive stimulation. The goal of this study was to improve adult human vascular smooth muscle cell orientation and elastic matrix synthesis within 3D tubular collagen gel constructs. We used a combination of elastogenic factors (EFs) previously tested in our lab, along with cyclic circumferential strains at low amplitude (2.

Tissue engineering and regenerative strategies to replicate biocomplexity of vascular elastic matrix assembly.

Cardiovascular tissues exhibit architecturally complex extracellular matrices, of which the elastic matrix forms a major component. The elastic matrix critically maintains native structural configurations of vascular tissues, determines their ability to recoil after stretch, and regulates cell signaling pathways involved in morphogenesis, injury response, and inflammation via biomechanical transduction. The ability to tissue engineer vascular replacements that incorporate elastic matrix superstructures unique to cardiac and vascular tissues is thus important to maintaining vascular homeostasis.

Induced elastic matrix deposition within three-dimensional collagen scaffolds.

The structural stability of a cyclically distending elastic artery and the healthy functioning of vascular smooth muscle cells (SMCs) within are maintained by the presence of an intact elastic matrix and its principal protein, elastin. The accelerated degradation of the elastic matrix, which occurs in several vascular diseases, coupled with the poor ability of adult SMCs to regenerate lost elastin, can therefore adversely impact vascular homeostasis. Similarly, efforts to tissue engineer elastic matrix structures are constrained by our inability to induce adult cells to synthesize tropoelastin precursors and to crosslink them into architectural mimics of native elastic matrices, especially within engineered constructs where SMCs/fibroblasts primarily deposit collagen in abundance.