"Introduction: Vascularization is crucial for proper implant survival and integration in the body. For an implant to be vascularized in vivo and thereby supplied with oxygen and the needed nutrients, the body’s blood vessels have to invade the implant first. This is a very slow and often insufficient process, especially in thicker tissues, which can result in implant loss. A solution for this are pre-vascularized, fibrin-based implants that can be attached to the blood vessels in vivo, thereby giving a faster and more sufficient blood supply throughout the whole tissue construct enabling implant survival.
Methodology: We here present a bioartificial tissue construct with a fibrin matrix of 5 mg/mL fibrinogen concentration, containing red fluorescent protein-labeled human umbilical vein endothelial cells (RFP-HUVEC) and adipose tissue-derived stem cells (ASC), facilitating capillary-like network formation. Cellularized fibrin gels were either supported by enclosing them in a high-concentration fibrin capsule, or by walls of the custom built flow chamber. Two fibrin-based vascular grafts were integrated on each side of the construct as an in- and outlet for flow. These were interconnected with microchannels penetrating the cellularized matrix. After polymerization of the fibrin matrix, microchannels were endothelialized with RFP-HUVEC as well. Tissue constructs were then perfused for four days at a flow rate of 18 mL/min at 2-3 mmHg, with feeding medium containing VEGF, FGF, Ascorbic Acid, Aprotinin, TPA and reduced serum supplement.
Results: After four days of perfusion, homogenous capillary-like network formation throughout the cellularized fibrin matrix could be observed. Interestingly, cells between endothelialized microchannels started to align during capillary formation. Moreover, a radial alignment of cells around microchannels could be observed, with occasional sprouting of endothelial cells off cellularized microchannels.
Conclusion: By perfusion of low-concentration fibrin gels, vascularization of a tissue construct can be achieved. This offers the opportunity for the generation of various tissue constructs by introducing tissue specific cell types into the construct."