2D and 3D collagen and fibrin biopolymers promote specific ECM and integrin gene expression by vascular smooth muscle cells

Collagen Type I and fibrin are polymeric proteins commonly used in the field of regenerative medicine as the foundational matrix of engineered tissues. We examined the response of vascular smooth muscle cells (VSMC) to both two-dimensional (2D) substrates as well as three-dimensional (3D) matrices of these biopolymers. Pure collagen Type I, pure fibrin and composite matrices consisting of 1: 1 mixtures of collagen and fibrin were studied. Relative gene expression of three ECM molecules (collagen Type I and III, and tropoelastin) and three integrin subunits (integrins alpha 1, beta 1 and beta 3) was determined over 7 days in culture using quantitative RT-PCR. Expression of all of these marker genes was up-regulated in 3D matrices, relative to 2D substrates. Tropoelastin, integrin alpha 1 and integrin beta 1 were highest in collagen matrices, while collagen III and integrin beta 3 expression were highest in pure fibrin, and collagen I expression was highest in the collagen -fibrin composite materials. Both the compositional and temporal expression patterns of these specific ECM-related genes were suggestive of a wound healing response. These results illuminate the short-term responses of VSMC to 2D and 3D biopolymer matrices, and have relevance to tissue engineering and cardiovascular biology.