Assessment of fibrin-collagen co-gels for generating microvesselsusing endothelial cell-lined microfluidics and multipotent stromal cell (MSC)-induced capillary morphogenesis.

One aspect of the challenge of engineering viable tissuesis the generation of perfusable microvessels of varying diameters. In this work, we take the approach of using hydrogel-based microfluidics seeded with endothelial cells (ECs) to form small artery/vein-like vessels, in conjunction with using the self-assembly behavior of ECs to form capillary-like vessels when co-cultured with multipotent stromal cells (MSCs). In exploring this approach, we focused on investigating collagen, fibrin, and various collagen-fibrin co-gel formulations for their potential suitability as serving as scaffold materials by surveying their angiogencity and mechanical properties. Fibrin and co-gels successfully facilitated multicellular EC sprouting, whereas collagen elicited a migration response of individual ECs, unless supplemented with the protein kinase C (PKC)-activator, phorbol 12-myristate 13-acetate. Collagen scaffolds were also found to severely contract when embedded with mesenchymal cells, but this contraction could be abrogated with the addition of fibrin. Increasing collagen content within co-gel formulations, however, imparted a higher compressive modulus and allowed for the reliable formation of intact hydrogel-based microchannels which could then be perfused. Given the bioactivity and mechanical benefits of fibrin and collagen, respectively, collagen-fibrin co-gels are a promising scaffold option for generating vascularized tissue constructs.