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

Abstract:
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. However, the vascular elastic matrix is particularly difficult to tissue engineer due to the inherently poor ability of adult vascular cells to synthesize elastin precursors and organize them into mature structures in a manner that replicates the biocomplexity of elastic matrix assembly during development. This review discusses current tissue engineering materials (e.g., growth factors and scaffolds) and methods (e.g., dynamic stretch and contact guidance) used to promote cellular synthesis and assembly of elastic matrix superstructures, and the limitations of these approaches when applied to smooth muscle cells, the primary elastin-generating cell type in vascular tissues. The potential application of these methods for in situ regeneration of disrupted elastic matrix at sites of proteolytic vascular disease (e.g., abdominal aortic aneurysms) is also discussed. Finally, the review describes the potential utility of alternative cell types to elastic tissue engineering and regenerative matrix repair. Future progress in the field is contingent on developing a thorough understanding of developmental elastogenesis and then mimicking the spatiotemporal changes in the cellular microenvironment that occur during that phase. This will enable us to tissue engineer clinically applicable elastic vascular tissue replacements and to develop elastogenic therapies to restore homeostasis in de-elasticized vessels.